KR20190043437A - 단백질 키나제 억제제로서의 헤테로고리 화합물 - Google Patents

단백질 키나제 억제제로서의 헤테로고리 화합물 Download PDF

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KR20190043437A
KR20190043437A KR1020170135515A KR20170135515A KR20190043437A KR 20190043437 A KR20190043437 A KR 20190043437A KR 1020170135515 A KR1020170135515 A KR 1020170135515A KR 20170135515 A KR20170135515 A KR 20170135515A KR 20190043437 A KR20190043437 A KR 20190043437A
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alkyl
pyrrolo
cyclopropanecarboxamide
pyridin
esi
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이혁우
지미경
김승찬
유하나
정수연
박지연
이예림
이호열
기소영
김동규
김명중
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씨제이헬스케어 주식회사
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Priority to KR1020170135515A priority Critical patent/KR20190043437A/ko
Priority to JOP/2018/0094A priority patent/JOP20180094A1/ar
Priority to PCT/KR2018/012270 priority patent/WO2019078619A1/en
Priority to MX2020003868A priority patent/MX2020003868A/es
Priority to AU2018353759A priority patent/AU2018353759B2/en
Priority to JP2020521905A priority patent/JP7112488B2/ja
Priority to US16/757,182 priority patent/US11524968B2/en
Priority to CA3082156A priority patent/CA3082156C/en
Priority to CN201880067864.1A priority patent/CN111372931B/zh
Priority to BR112020007684-8A priority patent/BR112020007684A2/pt
Priority to EP18869085.3A priority patent/EP3697787A4/en
Priority to RU2020115890A priority patent/RU2783723C2/ru
Publication of KR20190043437A publication Critical patent/KR20190043437A/ko

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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Abstract

본 발명은 단백질 키나제 억제 활성을 갖는 신규 화합물, 이의 입체이성질체 또는 이의 약제학적 허용가능한 염을 제공한다.
본 발명에 따른 화합물, 이의 입체이성질체 또는 이의 약제학적 허용가능한 염은 단백질 키나제 억제 활성을 나타냄으로써, 암, 자가면역질환, 신경질환, 대사질환 또는 감염 등의 단백질 키나제 관련 질환의 예방 또는 치료에 효과적이다.

Description

단백질 키나제 억제제로서의 헤테로고리 화합물 {Heterocylic compound as a protein kinase inhibitor}
본 발명은 단백질 키나제 활성을 억제함으로써 이와 관련된 질환의 예방 또는 치료에 유용하게 사용될 수 있는 신규 화합물 및 이의 용도에 관한 것이다.
단백질 키나제는 다른 단백질을 인산화시켜 단백질의 활성, 위치 및 기능을 조절하여 다양한 세포내 과정을 제어하는 효소이다. 이러한 단백질 키나제의 제어 기능 이상은 암, 자가면역질환, 신경질환, 대사질환 또는 감염 등의 질병 기작과 밀접하게 연관되어 있다.
JAK (Janus Kinase, 야누스키나제)는 아미노산 약 1150개로 이루어진 분자량 120~130 KDa 정도의 단백질로 JAK1, JAK2, JAK3, TYK2의 4종류로 구분된다. 야누스키나제는 염증성 사이토카인의 세포 내 수용체에 위치하며, 염증성 싸이토카인 (IL-2, IL-4, IL-6, IL-7, IL-9, IL15, IL-21, GM-CSF, G-CSF, EPO, TPO, IFN-a, IFN-b, IFN-g 등)이 수용체와 결합하고, 인산화 후 STAT 분자와 작용을 통해 염증성 사이토카인의 신호를 세포내로 전달한다. 이러한 다양한 염증성 사이토카인을 통한 신호 전달의 과도한 활성화는 우리 몸의 면역체계가 인체를 공격하는 결과를 나타내며, 이러한 결과로 자가면역질환이 발생한다. 따라서, 자가면역질환에서 이러한 염증성 싸이토카인의 수용체 키나제를 억제하는 약물의 개발을 통해 기존 치료제보다 개선된 치료 효과를 확인할 수 있을것으로 기대된다.
본 발명은 단백질 키나제 억제 활성을 나타내는 신규한 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용가능한 염을 제공하는 것을 목적으로 한다.
본 발명은 또한, 본 발명의 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용가능한 염의 제조방법을 제공하는 것을 목적으로 한다.
본 발명은, 본 발명의 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 단백질 키나제 관련 질환의 치료 또는 예방을 위한 약제학적 조성물을 제공함을 목적으로 한다.
본 발명은 또한, 치료학적 유효량의 본 발명의 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용가능한 염을 투여하는 단계를 포함하는 단백질 키나제 관련 질환의 치료 또는 예방을 위한 방법을 제공함을 목적으로 한다.
본 발명은 또한, 단백질 키나제 관련 질환의 예방 또는 치료용 약제의 제조를 위한 본 발명의 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용가능한 염의 용도를 제공함을 목적으로 한다.
단백질 키나제 억제제 화합물
상기 과제를 해결하기 위하여, 본 발명은 하기 화학식 1의 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용가능한 염을 제공한다.
[화학식 1]
Figure pat00001
상기 식에서,
X 는 C-A3 또는 N 이고,
Y 는 C-A4 또는 N 이고,
Z 는 N 또는 N-O 이고,
A1 내지 A4 는 각각 독립적으로 H 또는 C1-C6알킬, C1-C6알콕시, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, C(=O)-OH, C(=O)-O-C1-C6알킬, S(=O)2-C1-C6알킬, 아릴 또는 헤테로아릴이고,
B1 은 -(CH2)m-, -C(=O)-, -C(=S)-, -C(=NR1)-, -C(=O)-NR1-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -(CH2)m-의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있음},
B2는 H, C1-C6알킬, C3-C7시클로알킬, 5-6원 헤테로시클로알킬, 아릴, 헤테로아릴, C1-C6알킬-아릴 또는 C1-C6알킬-헤테로아릴이고 {여기서, C3-C7시클로알킬, 5-6원 헤테로시클로알킬, 아릴, 헤테로아릴, C1-C6알킬-아릴 또는 C1-C6알킬-헤테로아릴의 하나 이상의 H는 C1-C6알킬, 히드록시 또는 할로겐으로 치환될 수 있음},
B3 는 H 또는 C1-C6알킬이고,
Cyclic linker는 C3-C7시클로알킬, C3-C7시클로알케닐, 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고
C1 및 C2는 각각 독립적으로 H, C1-C6알킬, C1-C6알콕시, C1-C6히드록시알킬, C1-C6시아노알킬, C1-C6할로알킬, 히드록시, 시아노, 할로겐, C(=O)-OH, C(=O)-O-C1-C6알킬, S(=O)2-C1-C6알킬, 아릴 또는 헤테로아릴이고,
또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리 또는 스파이로 고리를 만들 수 있고,
D1 은 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
Figure pat00002
,
Figure pat00003
또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있고,
Figure pat00004
또는
Figure pat00005
의 하나 이상의 H는 C1-C6알킬, C1-C6히드록시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬로 치환될 수 있음},
D2 는 -C(=O)-, -C(=O)-CH2-C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -C(=O)-CH2-C(=O)- 의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
D3 는 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
Figure pat00006
또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있음},
D4 는 H, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, S(=O)2-C1-C6알킬, C3-C7시클로알킬,
Figure pat00007
, 아릴 또는 헤테로아릴이고
{여기서, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
C3-C7시클로알킬 또는
Figure pat00008
의 하나 이상의 H는 C1-C6알킬, C1-C6할로알킬, C1-C6시아노알킬, 시아노, 할로겐, -C(=O)-R4 또는 -C(=O)-O-R4 로 치환될 수 있고,
아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, C1-C6알콕시, C1-C6할로알킬, C1-C6히드록시알킬, C1-C6시아노알킬, C1-C6티오알킬, 히드록시, 시아노, 니트로, 할로겐, -C(=O)-R4, -C(=O)-NR1-R4, -S(=O)2-R4, -S(=O)2-NR1-R4, -NR1-R5,
Figure pat00009
, 아릴 또는 헤테로아릴로 치환될 수 있음 [이때,
Figure pat00010
의 하나 이상의 H는 C1-C6알킬 또는 (=O) 로 치환될 수 있음]},
R1 및 R2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
R3 는 H, C1-C6알킬, -C(=O)-R4, -C(=O)-O-R4, -S(=O)2-R4 또는 -S(=O)2-NR1-R4 이고 {여기서, W 가 -O-, -C(=O)- 또는 -S(=O)2- 인 경우 R3 는 아무 것도 아님 (null)},
R4 는 H, C1-C6알킬 또는 C1-C6할로알킬이고,
R5 는 H, C1-C6알킬,
Figure pat00011
, 아릴 또는 헤테로아릴이고 {여기서,
Figure pat00012
의 하나 이상의 H는 C1-C6알킬 또는 (=O) 로 치환될 수 있고, 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
V 는 -CH- 또는 -N- 이고,
W 는 -CH-, -N-, -O-, -S-, -C(=O)-, -S(=O)- 또는 -S(=O)2- 이고 {여기서, V 가 -CH- 인 경우 W 는 -CH- 가 아님},
a 내지 d 는 각각 독립적으로 1, 2 또는 3 이고,
m 은 1, 2 또는 3 이다.
본 발명의 일 구체예에 따르면,
X 는 C-A3 또는 N 이고,
Y 는 C-A4 또는 N 이고,
Z 는 N 또는 N-O 이고,
A1 내지 A4 는 각각 독립적으로 H 또는 C1-C6알킬 또는 C1-C6시아노알킬 이고,
B1 은 -(CH2)m-, -C(=O)-, -C(=S)-, -C(=NR1)-, -C(=O)-NR1-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -(CH2)m-의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있음},
B2는 H, C1-C6알킬, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴이고 {여기서, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
B3 는 H 또는 C1-C6알킬이고,
Cyclic linker는 C3-C7시클로알킬, C3-C7시클로알케닐, 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고,
C1 및 C2는 각각 독립적으로 H, C1-C6알킬, C1-C6할로알킬, 히드록시, 시아노, 할로겐, C(=O)-OH, C(=O)-O-C1-C6알킬, 또는 아릴이고,
또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리 또는 스파이로 고리를 만들 수 있고,
D1 은 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
Figure pat00013
,
Figure pat00014
또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있고,
Figure pat00015
,
Figure pat00016
또는
Figure pat00017
의 하나 이상의 H는 C1-C6알킬 또는 C1-C6시아노알킬로 치환될 수 있음},
D2 는 -C(=O)-, -C(=O)-CH2-C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -C(=O)-CH2-C(=O)- 의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
D3 는 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
Figure pat00018
또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 시아노로 치환될 수 있음},
D4 는 H, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, S(=O)2-C1-C6알킬, C3-C7시클로알킬,
Figure pat00019
, 아릴 또는 헤테로아릴이고
{여기서, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
C3-C7시클로알킬 또는
Figure pat00020
의 하나 이상의 H는 C1-C6알킬, C1-C6할로알킬, C1-C6시아노알킬, 시아노, 할로겐 또는 -C(=O)-O-R4 로 치환될 수 있고,
아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, C1-C6알콕시, C1-C6할로알킬, C1-C6티오알킬, 히드록시, 시아노, 니트로, 할로겐, -C(=O)-R4, -C(=O)-NR1-R4, -S(=O)2-R4, -S(=O)2-NR1-R4, -NR1-R5 또는
Figure pat00021
로 치환될 수 있음 [이때,
Figure pat00022
의 하나 이상의 H는 (=O) 로 치환될 수 있음]},
R1 및 R2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
R3 는 H, C1-C6알킬, -C(=O)-R4, -C(=O)-O-R4, -S(=O)2-R4 또는 -S(=O)2-NR1-R4 이고 {여기서, W 가 -O-, -C(=O)- 또는 -S(=O)2- 인 경우 R3 는 아무 것도 아님 (null)},
R4 는 H, C1-C6알킬 또는 C1-C6할로알킬이고,
R5 는 H,
Figure pat00023
또는 아릴이고 {여기서,
Figure pat00024
의 하나 이상의 H는 (=O) 로 치환될 수 있고, 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
V 는 -CH- 또는 -N- 이고,
W 는 -CH-, -N-, -O-, -S-, -C(=O)-, -S(=O)- 또는 -S(=O)2- 이고 {여기서, V 가 -CH- 인 경우 W 는 -CH- 가 아님},
a 내지 d 는 각각 독립적으로 1, 2 또는 3 이고,
m 은 1 또는 2 일 수 있다.
본 발명의 다른 구체예에 따르면,
X 는 C-A3 이고,
Y 는 C-A4 이고,
Z 는 N 또는 N-O 이고,
A1 내지 A4 는 각각 독립적으로 H 또는 C1-C6알킬 또는 C1-C6시아노알킬 이고,
B1 은 -(CH2)m-, -C(=O)-, -C(=S)-, -C(=NR1)-, -C(=O)-NR1-, -S(=O)2- 또는 아무 것도 아니고 (null),
B2는 H, C1-C6알킬, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴이고 {여기서, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
B3 는 H이고,
Cyclic linker는 C3-C7시클로알킬, C3-C7시클로알케닐, 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고,
C1 및 C2는 각각 독립적으로 H, C1-C6알킬, C1-C6할로알킬, 히드록시, 시아노, 할로겐, C(=O)-OH, C(=O)-O-C1-C6알킬, 또는 아릴이고,
또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리 또는 스파이로 고리를 만들 수 있고,
D1 은 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
Figure pat00025
,
Figure pat00026
또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있고,
Figure pat00027
,
Figure pat00028
또는
Figure pat00029
의 하나 이상의 H는 C1-C6알킬 또는 C1-C6시아노알킬로 치환될 수 있음},
D2 는 -C(=O)-, -C(=O)-CH2-C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -C(=O)-CH2-C(=O)- 의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
D3 는 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
Figure pat00030
또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 시아노로 치환될 수 있음},
D4 는 H, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6할로알킬, C1-C6시아노알킬, S(=O)2-C1-C6알킬, C3-C7시클로알킬,
Figure pat00031
, 아릴 또는 헤테로아릴이고
{여기서, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
C3-C7시클로알킬 또는
Figure pat00032
의 하나 이상의 H는 C1-C6알킬, C1-C6할로알킬, C1-C6시아노알킬, 시아노, 할로겐 또는 -C(=O)-O-R4 로 치환될 수 있고,
아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, C1-C6알콕시, C1-C6할로알킬, C1-C6티오알킬, 히드록시, 시아노, 니트로, 할로겐, -C(=O)-R4, -C(=O)-NR1-R4, -S(=O)2-R4, -S(=O)2-NR1-R4, -NR1-R5 또는
Figure pat00033
로 치환될 수 있음 [이때,
Figure pat00034
의 하나 이상의 H는 (=O) 로 치환될 수 있음]},
R1 및 R2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
R3 는 H, C1-C6알킬, -C(=O)-R4, -C(=O)-O-R4, -S(=O)2-R4 또는 -S(=O)2-NR1-R4 이고 {여기서, W 가 -O-, -C(=O)- 또는 -S(=O)2- 인 경우 R3 는 아무 것도 아님 (null)},
R4 는 H, C1-C6알킬 또는 C1-C6할로알킬이고,
R5 는 H,
Figure pat00035
또는 아릴이고 {여기서,
Figure pat00036
의 하나 이상의 H는 (=O) 로 치환될 수 있고, 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
V 는 -CH- 또는 -N- 이고,
W 는 -CH-, -N-, -O-, -S-, -C(=O)-, -S(=O)- 또는 -S(=O)2- 이고 {여기서, V 가 -CH- 인 경우 W 는 -CH- 가 아님},
a 내지 d 는 각각 독립적으로 1, 2 또는 3 이고,
m 은 1 또는 2 일 수 있다.
본 발명의 다른 구체예에 따르면,
X 는 C-A3 이고,
Y 는 N 이고,
Z 는 N 이고,
A1 내지 A3 는 각각 독립적으로 H 또는 C1-C6알킬 이고,
B1 은 -C(=O)- 이고,
B2는 C3-C7시클로알킬 또는 아릴이고 {여기서, C3-C7시클로알킬 또는 아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
B3 는 H 또는 C1-C6알킬이고,
Cyclic linker는 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고,
C1 및 C2는 각각 독립적으로 H, C1-C6알킬 또는 할로겐이고,
또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리를 만들 수 있고,
D1 은 -(CH2)m-, -NR1- 또는 아무 것도 아니고 (null),
D2 는 -C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null),
D3 는 -(CH2)m-, -NR1-, -O- 또는 아무 것도 아니고 (null),
D4 는 C1-C6알킬, C1-C6알케닐, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, C3-C7시클로알킬,
Figure pat00037
, 아릴 또는 헤테로아릴이고
{여기서, C3-C7시클로알킬 또는
Figure pat00038
의 하나 이상의 H는 C1-C6알킬 또는 시아노 로 치환될 수 있고,
아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, 시아노, 할로겐 또는 -C(=O)-NR1-R4 로 치환될 수 있음},
R1 은 H 또는 C1-C6알킬이고,
R4 는 H이고,
V 는 -CH- 또는 -N- 이고,
W 는 -O-또는 -S(=O)2- 이고,
a 및 b 는 각각 독립적으로 1, 2 또는 3 이고,
m 은 1 또는 2 일 수 있다.
본 발명의 다른 구체예에 따르면,
X 는 N 이고,
Y 는 C-A4 이고,
Z 는 N 이고,
A1, A2 및 A4 는 각각 독립적으로 H 또는 C1-C6알킬이고,
B1 은 -C(=O)- 이고,
B2는 C3-C7시클로알킬이고 {여기서, C3-C7시클로알킬의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
B3 는 H 이고,
Cyclic linker는 아릴이고
C1 및 C2는 각각 독립적으로 H, C1-C6알킬 또는 할로겐이고,
D1 은 -(CH2)m- 또는 -NR1-,
D2 는 -S(=O)2- 또는 아무 것도 아니고 (null),
D3 는 아무 것도 아니고 (null),
D4 는 C1-C6알킬, C1-C6할로알킬 또는 헤테로아릴이고
{여기서, C1-C6알킬 또는 C1-C6할로알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
헤테로아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
R1 은 H 이고,
m 은 1 또는 2 일 수 있다.
본 발명의 다른 구체예에 따르면,
X 는 N 이고,
Y 는 N 이고,
Z 는 N 이고,
A1 및 A2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
B1 은 -C(=O)- 이고,
B2는 C3-C7시클로알킬이고 {여기서, C3-C7시클로알킬의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
B3 는 H 이고,
Cyclic linker는 아릴이고
C1 및 C2는 각각 독립적으로 H, C1-C6알킬 또는 할로겐이고,
D1 은 -(CH2)m, -NR1-, -NR1- 또는 -O- 이고,
D2 는 -S(=O)2- 또는 아무 것도 아니고 (null),
D3 는 아무 것도 아니고 (null),
D4 는 C1-C6알킬, C1-C6할로알킬,
Figure pat00039
, 아릴 또는 헤테로아릴이고
{여기서, C1-C6알킬 또는 C1-C6할로알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
아릴 또는 헤테로아릴의 하나 이상의 H는 시아노 또는 할로겐로 치환될 수 있음},
R1 은 H 이고,
V 는 -N- 이고,
W 는 -O- 또는 -S(=O)2- 이고,
a 및 b 는 각각 독립적으로 1, 2 또는 3 이고,
m 은 1 또는 2 일 수 있다.
본 명세서를 통하여 화학식 (1)의 화합물을 정의함에 있어서는 다음과 같이 정의된 개념들이 사용된다. 하기 정의는 특별히 달리 지시되지 않는 한, 본 명세서 전체에 걸쳐서 개별적으로 또는 더욱 큰 군의 일부로서 사용되는 용어에도 적용된다.
용어 “알킬”은 단독으로 또는 “헤테로알킬”과 같이 조합하여 사용되는 경우에 각각 직쇄, 측쇄 또는 고리 모양의 탄화수소 라디칼을 의미하며, 각 탄소 원자는 하나 이상의 시아노, 히드록시, 알콕시, 옥소, 할로겐, 카보닐, 설포닐, 시아닐 등으로 임의로 치환될 수 있다.
용어 “알콕시” 는 -O-알킬을 말하며, 여기에서 알킬은 위에서 정의한 바와 같다.
용어 “헤테로알킬"은 N, O, S 중에서 선택된 헤테로 원자를 하나 이상 포함하는 알킬을 의미한다.
용어 “아릴”은 페닐, 나프틸 등을 포함하는 방향족 그룹을 의미하며, 하나 이상의 알킬, 알콕시, 할로겐, 하이드록시, 카보닐, 설포닐, 시아닐 등으로 임의 치환될 수 있다.
용어 “헤테로 사이클”은 N, O, S 중에서 선택된 1내지 4개의 헤테로 원자를 포함하며, 임의로 벤조 또는 사이클로알킬과 융합될 수 있는, 포화 또는 부분적으로 포화 또는 방향족인 형태를 지칭한다.
용어 “할로(겐)”은 플루우로, 클로로, 브로모 및 아이오도로 선택되는 치환체를 의미한다.
이밖에 본 명세서에서 사용된 용어들과 약어들은 달리 정의되지 않는 한, 그 본래의 의미를 갖는다.
본 발명에서, 상기 화학식 1로 표시되는 화합물의 대표적인 예는 다음과 같다.
Figure pat00040
Figure pat00041
Figure pat00042
Figure pat00043
Figure pat00044
Figure pat00045
Figure pat00046
Figure pat00047
Figure pat00048
Figure pat00049
Figure pat00050
Figure pat00051
Figure pat00052
Figure pat00053
Figure pat00054
Figure pat00055
Figure pat00056
Figure pat00057
Figure pat00058
Figure pat00059
Figure pat00060
Figure pat00061
Figure pat00062
Figure pat00063
Figure pat00064
Figure pat00065
Figure pat00066
Figure pat00067
Figure pat00068
Figure pat00069
Figure pat00070
Figure pat00071
Figure pat00072
Figure pat00073
Figure pat00074
Figure pat00075
Figure pat00076
Figure pat00077
Figure pat00078
Figure pat00079
Figure pat00080
Figure pat00081
Figure pat00082
Figure pat00083
Figure pat00084
Figure pat00085
Figure pat00086
Figure pat00087
이하에서는 편의상 다르게 지시되지 않는 한, 화학식 1의 화합물은 본 발명의 화학식 1의 화합물, 이의 입체이성질체 또는 이의 약제학적으로 허용되는 염을 모두 포함하여 지칭한다.
본 발명에 따른 화합물은 약제학적으로 허용되는 염을 형성할 수 있다. 이러한 약제학적으로 허용되는 염에는 무독성 산부가염을 형성하는 산, 예를 들면 염산, 황산, 질산, 인산, 브롬화수소산, 요오드화수소산 등과 같은 무기산, 타타르산, 포름산, 시트르산, 아세트산, 트리클로로아세트산, 트리플루오로아세트산, 글루콘산, 벤조산, 락트산, 푸마르산, 말레인산 등과 같은 유기 카본산, 메탄설폰산, 벤젠설폰산, p-톨루엔설폰산 또는 나프탈렌설폰산 등과 같은 설폰산 등에 의해 형성된 산부가염이 포함된다. 본 발명에 따른 화학식 1의 화합물은 통상적인 방법에 의해 그의 염으로 전환시킬수 있다.
한편, 본 발명에 따른 화합물들은 비대칭 탄소를 가질수 있으며, R 또는 S 이성질체, 라세믹체, 부분입체이성체 혼합물 및 개개 부분입체이성질체로서 존재할 수 있으며, 이들 모든 이성질체 및 혼합물은 본 발명의 범위에 포함된다. 즉, 화학식 1의 구조에 비대칭 탄소(들)가 포함되는 경우에는 방향이 별도로 기재되어 있지 않는 한, 입체 이성질체들(stereoisomer) 모두가 포함되는 것으로 이해하여야 한다.
화학식 1 화합물의 제조방법
본 발명은 또한 화학식 1의 화합물을 제조하는 방법을 제공한다. 이하에서 본 발명의 이해를 돕기 위해 화학식 1의 화합물의 제조방법을 예시적인 반응식에 기초하여 설명하지만, 본 발명이 속한 분야에서 통상의 지식을 가진 자라면 화학식 1의 구조를 바탕으로 다양한 방법에 의해 화학식 1의 화합물을 제조할 수 있으며, 이러한 방법들은 모두 본 발명의 범주에 포함되는 것으로 해석되어야 한다. 즉, 본 명세서에 기재되어 있거나, 선행기술에 개시된 여러 합성법들을 임의로 조합하여 화학식 1의 화합물의 제조가 가능하며, 이는 본 발명의 범위 내에 속하는 것으로 이해하여야 한다. 하기 반응식에서, 달리 나타내지 않는 한, 모든 치환기는 앞서 정의된 바와 같다.
본 발명의 화합물들에서 사용되는 산, 염기, 및 반응 용매는 이 분야에서 일반적으로 사용되는 것을 제한없이 사용할 수 있다. 예컨대, 산으로는 염산, 황산, 질산, 인산, 브롬화수소산, 요오드화수소산등과 같은 무기산과 타타르산, 포름산, 시트르산, 아세트산, 아디핀산, 트리클로로아세트산, 트리플루오로아세트산, 글루콘산, 벤조산, 락트산, 푸마르산, 말레인산등과 같은 유기 카본산, 메탄설폰산, 벤젠설폰산, p-톨루엔설폰산 또는 나프탈렌설폰산 등과 같은 설폰산을 사용 할 수 있고, 염기로는 NaH, K2CO3, Na2CO3, NaHCO3, K3PO4, KOH, NaOH, LiOH, n-BuLi, sec-BuLi, LiHMDS 등이 사용될 수 있으며, 반응용매는 DCM, THF, Dioxane, MeOH, EtOH, Hexane, EtOAC, Ether, DMF, DMSO, toluene, xylene 등 또는 이들의 혼합용매 등이 사용될 수 있다.
본 발명에 따른 상기 화학식 1 화합물의 합성방법은 하기 반응식 1또는 반응식 2로 예시될 수 있다.
[반응식1]
Figure pat00088
상기 반응식 1에서
A2, B1, B2, C1, C2, X, Y, Z, cyclic linker는 화학식 (1)에서 정의한 바와 같으며,
D과 D'은 화학식 (1)에서 정의한 D1-D2-D3-D4를 도입하기 위한 유사체 또는 D1-D2-D3-D4 그 자체이다.
상기 반응식 1에서 중간체 화합물
Figure pat00089
은 halo = OTf인 경우 하기 반응식 1-1의 방법을 통하여 합성될수 있다.
[반응식 1-1]
Figure pat00090
상기 반응식 1-1에서
C1, C2, D’ 는 상기 반응식 1과 동일하며,
( )n 는 다각형의 고리 화합물을 나타낸다.
상기 반응식 1의 방법 이외에 하기 반응식 2를 통하여 합성될 수 있다.
[반응식 2]
Figure pat00091
상기 반응식 2에서
화합물 (III)는 반응식 1의 화합물 (III)에 해당한다.
A2, B1, B2, C1, C2, X, Y, Z는 화학식 (1)에서 정의한 바와 같으며,
D과 D'은 화학식 (1)에서 정의한 D1-D2-D3-D4를 도입하기 위한 유사체 또는 D1-D2-D3-D4 그 자체이다.
상기 반응식 1에서 화합물 (I)는 통상적으로 구매 가능하거나 합성될 수 있다.
본 발명의 화학식 1 화합물은 상기 반응식 1~2의 생성물로부터 결정화, 실리카겔 관 크로마토그래피등과 같은 여러 방법에 의해 분리 또는 정제될 수 있다. 이와같이, 본 발명의 화합물, 그것의 제조를 위한 개시물, 중간체 등은 다양한 방법들에 의해 합성될 수 있으며, 이러한 방법들은 화학식 1의 화합물의 제조와 관련하여 본 발명의 범주에 포함되는 것으로 해석되어야 한다.
화학식 I 화합물을 포함하는 조성물, 이의 용도, 이를 이용한 치료방법
본 발명은 하기 화학식 I 로 표시되는 화합물, 이의 입체이성질체, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 단백질 키나제 관련 질환의 치료 또는 예방용 약학적 조성물을 제공한다.
[화학식 I]
Figure pat00092
상기 화학식 1 은 위에서 정의한 바와 같다.
본 발명의 화학식 1 화합물은 단백질 키나제 억제 활성을 나타냄으로써 단백질 키나제 관련 질환의 예방 또는 치료에 현저한 효과를 보인다.
본 발명에 있어서, 상기 단백질 키나제 관련 질환은 암, 자가면역질환, 신경질환, 대사질환 또는 감염을 포함한다.
본 발명의 화학식 1 로 표시되는 화합물, 이의 입체이성질체 또는 이의 약제학적으로 허용가능한 염은 단백질 키나제 억제 활성이 있어 단백질 키나제 관련 질환에 대한 예방 또는 치료 효과가 현저히 우수하다.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나, 하기의 실시예는 본 발명을 더욱 쉽게 이해하기 위하여 제공되는 것일 뿐, 실시예에 의하여 본 발명이 한정되는 것은 아니다.
본 발명의 화합물을 합성하기 위한 출발 물질의 다양한 합성법이 알려져 있으며, 상기 출발 물질이 시판되고 있는 경우는 공급처로부터 구매하여 사용할 수 있다. 시약 공급처로는 Sigma-Aldrich, TCI, Wako, Kanto, Fluorchem, Acros, Alfa, Fluka, Combi-Blocks, Dae-Jung 등의 회사가 있으나 이에 한정되는 것은 아니다. 또한, 다른 식으로 규정되는 경우를 제외하고 시판된 모든 물질은 추가적으로 정제하지 않고 사용하였다.
이하, 하기의 실시예는 본 발명의 범위 내에서 당업자에 의해 적절히 수정, 변경될 수 있다.
제조예 : N-(4-(4,4,5,5- 테트라메틸 -1,3,2- 다이옥사보란 -2-일)-1-토실-1H- 피 롤로[2,3-b]피리딘-6-일)사이클로프로판카복사마이드의 합성
Figure pat00093
[단계 1] 4-클로로-1H-피롤로[2,3-b]피리딘 7-옥사이드 3-클로로벤조산염의 합성
Figure pat00094
4-클로로-7-아자인돌(15.0g, 98.3mmol)을 n-부틸아세테이트/n-헵탄 = 3/5(v/v), 800ml에 녹이고, 0 oC에서 m-클로로퍼옥시벤조산(77%, 24.2g, 108.1mmol)을 천천히 적가한 후, 실온에서 12시간 동안 교반하였다. 생성된 고체를 여과하고 감압 건조하여 표제 화합물(30g, 94%)을 얻었다.
1H NMR (400 MHz, DMSO-d6) δ 13.37 (br s, 1H), 12.90 (br s, 1H), 8.15 (d, J = 6.6 Hz, 1H), 7.89 (m, 2H) 7.68 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 3.1 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 7.20 (d, J = 6.6 Hz, 1H), 6.58 (d, J = 3.1 Hz, 1H).
MS (ESI+) m/z 169, 171 (M+H)+
[단계 2] 4-클로로-1H-피롤로[2,3-b]피리딘-6-아민의 합성
Figure pat00095
단계 1에서 얻은 화합물(30g, 92.3mmol)을 아세토니트릴(300ml)에 현탁하고 디메틸셀페이트(9.6ml, 101.5mmol)를 실온에서 적가한 후, 55 oC로 가온하여 12시간 동안 교반하였다.
반응 혼합물을 0 oC로 냉각하고 과량의 암모니아에탄올 용액을 가하고 45 oC로 가온하여 3일 동안 교반하였다. 실온으로 냉각하여 불용성 고체를 여과하여 제거하고 여액을 감압 농축하여 디클로로메탄(1L)에 녹인후, 10% 탄산나트륨 수용액으로 세척하고 무수 마그네슘셀페이트로 건조한 다음 필터한 여액을 감압농축하였다. 관크로마토그래피로 분리하여 표제 화합물(10g, 42.4mmol)을 얻었다.
1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 7.00 (s, 1H), 6.33 (s, 1H), 6.19 (s, 1H), 5.83 (s, 2H)
MS (ESI+) m/z 168, 170 (M+H)+
[단계 3] N-(4-클로로-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판카복사마이드의 합성
Figure pat00096
단계 2에서 얻은 화합물(11.0g, 65.6mmol)을 피리딘(100ml)에 녹이고 사이클로프로판카보닐클로라이드(7.5g, 72.2mmol)을 0 oC에서 천천히 적가한 후, 동일 온도에서 1시간 동안 교반하였다. 반응 혼합물을 물(350ml)에 가하고 생성된 고체를 여과하고 감압건조하여 표제 화합물(12.7g, 53.9mmol)을 얻었다.
1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 10.79(s, 1H), 8.02(s, 1H), 7.44(d, 1H), 6.25(d, 1H), 2.00(m, 1H), 0.88(m, 4H)
MS (ESI+) m/z 236, 238 (M+H)+
[단계 4] N-(4-클로로-1-토실-1H-피롤로[2,3-b]피리딘-6-일) 사이클로프로판 카복사마이드의 합성
Figure pat00097
단계 3에서 얻은 화합물(12.7g, 53.9mmol)을 디메틸포름아미드(100ml)에 녹이고 소듐하이드라이드(3.2g, 80.8mmol)를 0 oC에서 천천히 적가한 후, 토실클로라이드(11.3g, 59.3mmol)를 천천히 적가하여 30분간 교반하였다. 에틸아세테이트(300ml)를 가하고 물(300ml, 2회)로 세척한 후, 무수마그네슘셀페이트로 건조한 다음 필터한 여액을 감압증류하였다. 관크로마토그래피로 분리하여 표제 화합물(13.0g, 33.3mmol)을 얻었다.
1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.16 (m, 3H), 7.80 (s, 1H), 7.42 (m, 2H), 6.74 (s, 1H), 2.34 (s, 3H), 2.08 (m, 1H), 0.87 (m, 4H)
MS (ESI+) m/z 390, 392 (M+H)+
[단계 5] N-(4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보란-2-일)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판카복사마이드의 합성
Figure pat00098
단계 4에서 얻은 화합물 (20.0g, 51.3mmol)과 디피나콜보란(26.0g, 102.6mmol), 팔라듐아세테이트(0.2g, 1.02mmol), 2-(디사이클로헥실)포스핀바이페닐(0.7g, 2.05mmol), 칼륨아세테이트(10.1g, 102.6mmo)을 다이옥산(200ml)에 가하고 100 oC에서 2시간 동안 가온하였다. 실온으로 냉각하고 감압증류 후, 디클로로메탄(300ml)을 가하고 증류수(300ml, 2회)로 세척하였다. 분리한 유기층을 무수 마그네슘셀페이트로 건조한 다음 필터한 여액을 감압 증류하였다. 관크로마토그래피로 분리하여 표제 화합물(24.0g, 49.8mmol)을 얻었다.
1H NMR (400 MHz, DMSO-d6) δ 10.75 (s, 1H), 8.34 (s, 1H), 8.16 (d, 2H), 7.74 (d, 1H), 7.41 (d, 2H), 6.82 (d, 1H), 2.33 (s, 3H), 2.15 (m, 1H), 1.30 (s, 12H), 0.87 (m, 4H)
실시예 1: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-3- fluorophenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00099
[단계 1]
Figure pat00100
상기 반응식 3로부터 제조한 N-(4-클로로-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridine-6-yl)cyclopropanecarboxamide) 4.0 g (10.3 mmol)을 DMF/H2O = 2:1 용액에 용해시키고, 2-플루오로-4-(4,4,5,5-테트라메틸-1,3,2-디옥사보롤란-2-일)아닐린 2.7 g (12.4 mmol), Pd(dppf)Cl2 1.3 g (1.5 mmol), K3PO4 2.6 g (12.4 mmol)을 넣고, 80 ~ 90 oC 에서 1시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 물을 첨가, 에틸아세테이트로 추출하였다. 추출한 용액은 무수 황산마그네슘으로 건조하고, 감압 농축하여 잔여물을 수득하였다. 잔여물은 실리카겔 컬럼크로마토그래피 (n-헥산 / 에틸아세테이트 = 2:1)에서 분리하여 생성물 N-(4-(4-아미노-3-플루오로페닐)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-amino-3-fluorophenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine-6-yl)cyclopropanecarboxamide)를 수득하였다.
MS(ESI+) m/z 465 (M+H)+
[단계 2]
Figure pat00101
상기 단계 1에서 얻어진 N-(4-(4-아미노-3-플루오로페닐)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (100 mg)을 디클로로메탄에 넣고, Et3N, 3당량을 첨가하였다. 상기 혼합물에 에탄설포닐 클로라이드 2당량을 넣고, 실온에서 교반하였다. 반응이 완료되면 상기 혼합물을 d-HCl을 첨가하고, 디클로로메탄으로 추출하여, 유기층을 분리하였다. 혼합물을 농축 후, MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 ~ 40 oC에서 4 시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온으로 냉각시키고, 교반하면서 포화된 NH4Cl 수용액을 첨가하였다. 생성된 고체를 여과하여 N-(4-(4-(에틸술폰아미도)-3-플루오로페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.66 (s, 1H), 9.82 (s, 1H), 8.02 (s, 1H), 7.64 - 7.52 (m, 3H), 7.49 - 7.41 (m, 1H), 6.61 - 6.53 (m, 1H), 3.18 (q, J = 7.2 Hz, 2H), 2.04 (dd, J = 5.0, 10.1 Hz, 1H), 1.29 (t, J = 7.3 Hz, 3H), 0.89 - 0.78 (m, 4H).
MS(ESI+) m/z 403 (M+H)+
실시예 2 내지 213
이하 실시예 2 내지 실시예 213에서는, 실시예 1과 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 제조하였다.
실시예 2: N-(4-(4-((3,4- 디플루오로페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3,4-difluorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00102
MS(ESI+) m/z 469 (M+H)+
실시예 3: N-(4-(4-((3- 플루오로프로필 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-fluoropropyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00103
1H NMR (400 MHz, Methanol-d4) δ 7.89 (s, 1H), 7.82 - 7.74 (m, 2H), 7.48 - 7.37 (m, 2H), 7.32 (d, J = 3.6 Hz, 1H), 6.60 (d, J = 3.6 Hz, 1H), 4.59 (s, 1H), 4.47 (s, 1H), 3.27 (d, J = 5.6 Hz, 1H), 2.32 - 2.10 (m, 2H), 1.12 (d, J = 6.1 Hz, 1H), 0.95 (ddt, J = 3.1, 8.1, 40.7 Hz, 5H).
MS(ESI+) m/z 417 (M+H)+
실시예 4: N-(4-(4-( 에틸술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido ) phenyl )-1H- pyrrolo[2,3- b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00104
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.59 (s, 1H), 10.01 (s, 1H), 7.99 (s, 1H), 7.75 - 7.63 (m, 2H), 7.46 - 7.29 (m, 3H), 6.54 (dd, J = 1.9, 3.5 Hz, 1H), 3.17 (d, J = 7.4 Hz, 2H), 2.06 (d, J = 16.6 Hz, 1H), 1.23 (t, J = 7.3 Hz, 4H), 0.89 - 0.75 (m, 4H).
MS(ESI+) m/z 385 (M+H)+
실시예 5: N-(4-(4-( 프로필술포닐아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( propylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00105
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 10.00 (s, 1H), 8.00 (s, 1H), 7.81 - 7.64 (m, 2H), 7.38 (ddd, J = 2.4, 6.2, 8.6 Hz, 3H), 6.54 (dd, J = 1.9, 3.5 Hz, 1H), 3.22 - 3.05 (m, 2H), 2.06 (d, J = 16.5 Hz, 1H), 1.72 (td, J = 6.2, 8.3, 8.8 Hz, 2H), 0.96 (t, J = 7.4 Hz, 4H), 0.81 (ddd, J = 2.6, 6.4, 10.6 Hz, 5H).
MS(ESI+) m/z 399 (M+H)+
실시예 6: N-(4-(4-( 부틸술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-( butylsulfonamido ) phenyl )-1H- pyrrolo[2,3- b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00106
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.59 (s, 1H), 10.13 - 9.90 (m, 1H), 7.99 (s, 1H), 7.72 - 7.64 (m, 2H), 7.42 - 7.30 (m, 3H), 6.54 (dd, J = 1.8, 3.5 Hz, 1H), 3.21 - 3.10 (m, 2H), 2.09 - 1.99 (m, 1H), 1.73 - 1.61 (m, 2H), 1.38 (dt, J = 7.5, 15.0 Hz, 2H), 0.89 - 0.75 (m, 7H).
MS(ESI+) m/z 413 (M+H)+
실시예 7: N-(4-(4-( 시클로헥산술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclohexanesulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00107
MS(ESI+) m/z 439 (M+H)+
실시예 8: N-(4-(4-((2- 플루오로에틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2-fluoroethyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00108
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.73 (s, 1H), 7.86 (s, 1H), 7.61 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.5 Hz, 1H), 7.37 (t, J = 2.9 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.60 (s, 1H), 2.74 (t, J = 7.0 Hz, 2H), 2.02 (d, J = 7.9 Hz, 1H), 1.24 (s, 2H), 0.93 - 0.76 (m, 4H).
MS(ESI+) m/z 403 (M+H)+
실시예 9: N-(4-(4-((1,1- 디옥시도테트라히드로 -2H- 티오피란 )-4- 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1,1-dioxidotetrahydro-2H-thiopyran)-4-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00109
MS(ESI+) m/z 489 (M+H)+
실시예 10: N-(4-(4-((1,1- 디옥시도테트라히드로티오펜 )-3- 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1,1-dioxidotetrahydrothiophene)-3-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00110
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.61 (s, 1H), 10.41 (s, 1H), 8.00 (s, 1H), 7.75 - 7.66 (m, 2H), 7.44 - 7.34 (m, 3H), 6.54 (dd, J = 1.9, 3.7 Hz, 1H), 4.30 - 4.19 (m, 1H), 3.52 (dd, J = 9.4, 14.0 Hz, 1H), 3.27 - 3.18 (m, 2H), 2.43 - 2.33 (m, 1H), 2.03 (d, J = 7.4 Hz, 1H), 0.81 (dt, J = 4.3, 9.9 Hz, 4H).
MS(ESI+) m/z 475 (M+H)+
실시예 11: N-(4-(4-((1,1- 디옥시도티에탄 )-3- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1,1-dioxidothietane)-3-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00111
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (d, J = 6.0 Hz, 1H), 10.49 (d, J = 13.3 Hz, 1H), 8.01 (d, J = 3.0 Hz, 1H), 7.78 - 7.69 (m, 2H), 7.46 - 7.36 (m, 3H), 6.58 - 6.48 (m, 2H), 4.68 - 4.57 (m, 2H), 4.52 - 4.40 (m, 2H), 2.03 (s, 2H), 0.83 - 0.76 (m, 4H)
MS(ESI+) m/z 461 (M+H)+
실시예 12: N-(4-(4-((6- 클로로피리딘 )-3- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((6- chloropyridine )-3-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00112
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.78 (s, 1H), 10.59 (s, 1H), 8.79 (d, J = 2.6 Hz, 1H), 8.19 (dd, J = 2.6, 8.5 Hz, 1H), 7.96 (s, 1H), 7.76 (d, J = 8.5 Hz, 1H), 7.64 (d, J = 8.1 Hz, 2H), 7.38 (t, J = 3.0 Hz, 1H), 7.28 (d, J = 8.3 Hz, 2H), 6.49 (d, J = 3.4 Hz, 1H), 2.03 (s, 1H), 0.86 - 0.75 (m, 4H)
MS(ESI+) m/z 468, 480 (M+H)+
실시예 13: N-(4-(4-((4- 플루오로페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-fluorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00113
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.56 (d, J = 15.6 Hz, 2H), 7.94 (s, 1H), 7.92 - 7.83 (m, 2H), 7.60 (d, J = 8.3 Hz, 2H), 7.46 - 7.34 (m, 3H), 7.25 (d, J = 8.5 Hz, 2H), 6.48 (dd, J = 1.9, 3.7 Hz, 1H), 2.02 (d, J = 8.7 Hz, 1H), 0.80 (q, J = 5.9, 8.6 Hz, 4H)
MS(ESI+) m/z 451 (M+H)+
실시예 14: N-(4-(4-((4- 클로로페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-chlorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00114
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.58 (s, 2H), 7.94 (s, 1H), 7.87 - 7.75 (m, 2H), 7.62 (dd, J = 8.2, 18.3 Hz, 4H), 7.37 (t, J = 3.1 Hz, 1H), 7.24 (d, J = 8.2 Hz, 2H), 6.48 (dd, J = 1.9, 3.6 Hz, 1H), 2.02 (d, J = 9.2 Hz, 1H), 0.79 (t, J = 7.2 Hz, 4H).
MS(ESI+) m/z 467, 469 (M+H)+
실시예 15: N-(4-(4-((1- 메틸 -1H-이미다졸)-5- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1-methyl-1H-imidazole)-5-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00115
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.58 (s, 1H), 10.45 (s, 1H), 7.92 (d, J = 22.8 Hz, 2H), 7.75 (s, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.37 (t, J = 3.0 Hz, 1H), 7.31 (d, J = 8.2 Hz, 2H), 6.50 (s, 1H), 3.67 (s, 3H), 2.03 (s, 1H), 0.85 - 0.76 (m, 4H).
MS(ESI+) m/z 437 (M+H)+
실시예 16: N-(4-(4-((1- 메틸 -1H- 피라졸 )-4- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1-methyl-1H-pyrazole)-4-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00116
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.59 (s, 1H), 10.36 (s, 1H), 8.29 (s, 1H), 7.97 (s, 1H), 7.75 (s, 1H), 7.63 (d, J = 8.3 Hz, 2H), 7.38 (t, J = 3.0 Hz, 1H), 7.34 - 7.25 (m, 2H), 6.51 (dd, J = 1.9, 3.7 Hz, 1H), 3.84 (s, 3H), 2.04 (d, J = 7.0 Hz, 1H), 0.80 (tt, J = 3.8, 10.6 Hz, 4H).
MS(ESI+) m/z 437 (M+H)+
실시예 17: 4 -(N-(4-(6-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)술파모일)벤즈아미드 (4-(N-(4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)sulfamoyl)benzamide)의 합성
Figure pat00117
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.62 (s, 1H), 10.59 (s, 1H), 8.11 (s, 1H), 7.99 (d, J = 8.2 Hz, 2H), 7.93 (s, 1H), 7.89 (d, J = 8.1 Hz, 2H), 7.61 (d, J = 8.5 Hz, 2H), 7.57 (s, 1H), 7.39 - 7.34 (m, 1H), 7.28 (d, J = 8.3 Hz, 2H), 6.47 (d, J = 3.0 Hz, 1H), 2.03 (s, 1H), 0.84 - 0.76 (m, 4H).
MS(ESI+) m/z 476 (M+H)+
실시예 18: N-(4-(4-((1- 아세틸피페리딘 )-4- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1-acetylpiperidine)-4-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00118
1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.26 (s, 1H), 8.17 (s, 1H), 7.73 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H), 6.81 (s, 1H), 6.62 (d, J = 3.1 Hz, 1H), 4.72 (d, J = 12.9 Hz, 1H), 3.93 (d, J = 14.0 Hz, 1H), 3.49 (s, 3H), 3.28 (d, J = 12.3 Hz, 1H), 3.06 (t, J = 12.9 Hz, 1H), 2.55 (t, J = 12.5 Hz, 1H), 2.15 (d, J = 9.9 Hz, 2H), 2.09 (s, 3H), 1.85 (d, J = 12.2 Hz, 2H), 1.13 (d, J = 3.9 Hz, 3H), 0.95 - 0.78 (m, 9H).
MS(ESI+) m/z 482 (M+H)+
실시예 19: N-(4-(4-((4- 이소프로폭시페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-isopropoxyphenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00119
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.58 (s, 2H), 7.95 - 7.84 (m, 3H), 7.59 (d, J = 8.2 Hz, 2H), 7.39 - 7.19 (m, 6H), 6.54 - 6.38 (m, 1H), 2.03 (s, 1H), 0.85 - 0.77 (m, 4H).
MS(ESI+) m/z 491 (M+H)+
실시예 20: N-(4-(4-((4- 브로모페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-bromophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00120
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 7.93 (s, 1H), 7.72 (dd, J = 8.0, 5.5 Hz, 4H), 7.55 (d, J = 8.5 Hz, 2H), 7.39 - 7.33 (m, 1H), 7.18 (d, J = 8.6 Hz, 2H), 6.53 - 6.44 (m, 1H), 2.03 (s, 1H), 0.86 - 0.74 (m, 4H).
MS(ESI+) m/z 512 (M+H)+
실시예 21: N-(4-(4-((4- 시아노페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-cyanophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00121
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.67 (s, 1H), 10.59 (s, 1H), 8.03 - 7.84 (m, 5H), 7.61 (d, J = 8.3 Hz, 2H), 7.39 - 7.23 (m, 3H), 6.48 (s, 1H), 2.03 (s, 1H), 0.82 - 0.75 (m, 4H).
MS(ESI+) m/z 458 (M+H)+
실시예 22: N-(4-(4-((2,3- 디히드로벤조푸란 )-5- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2,3-dihydrobenzofuran)-5-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00122
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.58 (s, 1H), 10.36 (s, 1H), 7.94 (s, 1H), 7.68 (s, 1H), 7.63 - 7.55 (m, 3H), 7.40 - 7.32 (m, 1H), 7.29 - 7.21 (m, 2H), 6.88 (d, J = 8.4 Hz, 1H), 6.52 - 6.43 (m, 1H), 4.60 (t, J = 8.7 Hz, 2H), 3.22 (t, J = 8.8 Hz, 2H), 2.03 (s, 1H), 0.84 - 0.74 (m, 4H).
MS(ESI+) m/z 475 (M+H)+
실시예 23: N-(4-(4-((6- 메톡시피리딘 )-3- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((6- methoxypyridine )-3-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00123
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.59 (s, 2H), 8.64 - 8.54 (m, 1H), 8.07 - 7.92 (m, 2H), 7.63 (d, J = 8.1 Hz, 2H), 7.39 - 7.26 (m, 3H), 7.00 (d, J = 8.6 Hz, 1H), 6.49 (s, 1H), 3.89 (s, 4H), 2.03 (s, 1H), 0.82 - 0.75 (m, 4H).
MS(ESI+) m/z 464 (M+H)+
실시예 24: N-(4-(4-( 페닐술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-( phenylsulfonamido ) phenyl )-1H- pyrrolo[2,3- b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00124
1H NMR (400 MHz, DMSO-d6) δ 11.50 (d, J = 7.6 Hz, 1H), 10.55 (d, J = 22.8 Hz, 2H), 7.93 (s, 1H), 7.89 - 7.80 (m, 2H), 7.69 - 7.54 (m, 5H), 7.40 - 7.34 (m, 1H), 7.27 (d, J = 8.7 Hz, 2H), 6.53 - 6.38 (m, 1H), 2.02 (d, J = 8.1 Hz, 1H), 0.80 (q, J = 8.4, 6.4 Hz, 4H).
MS(ESI+) m/z 433 (M+H)+
실시예 25: N-(4-(4-((3- 플루오로페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-fluorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00125
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.60 (d, J = 19.3 Hz, 2H), 7.94 (s, 1H), 7.71 - 7.57 (m, 5H), 7.49 (t, J = 7.5 Hz, 1H), 7.41 - 7.33 (m, 1H), 7.31 - 7.16 (m, 2H), 6.56 - 6.43 (m, 1H), 2.03 (d, J = 9.3 Hz, 1H), 0.87 - 0.65 (m, 4H).
MS(ESI+) m/z 451 (M+H)+
실시예 26: N-(4-(4-((3- 클로로페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-chlorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00126
1H NMR (400 MHz, Chloroform-d) δ 7.94 - 7.77 (m, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.58 (dd, J = 6.6, 4.3 Hz, 2H), 7.51 - 7.43 (m, 1H), 7.36 (t, J = 7.9 Hz, 1H), 7.28 - 7.18 (m, 4H), 6.58 (d, J = 3.6 Hz, 1H), 1.89 (tt, J = 8.6, 4.6 Hz, 1H), 1.09 - 1.01 (m, 3H), 0.92 (dq, J = 7.8, 4.1 Hz, 2H), 0.87 - 0.72 (m, 4H).
MS(ESI+) m/z 467, 469 (M+H)+
실시예 27: N-(4-(4-((4- 메틸페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4- methylphenyl ) sulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00127
1H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 10.46 (s, 1H), 7.87 (s, 1H), 7.62 (d, J = 7.9 Hz, 2H), 7.32 (dd, J = 19.4, 5.6 Hz, 3H), 7.18 (d, J = 7.9 Hz, 2H), 6.94 (d, J = 8.3 Hz, 2H), 6.56 - 6.44 (m, 1H), 2.29 (s, 3H), 2.00 (d, J = 11.3 Hz, 1H), 0.88 - 0.66 (m, 4H).
MS(ESI+) m/z 447 (M+H)+
실시예 28: N-(4-(4-((4-( 메틸티오 )페닐) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-(methylthio)phenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00128
1H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 10.44 (s, 1H), 7.86 (s, 1H), 7.74 - 7.55 (m, 2H), 7.30 (dd, J = 14.1, 5.6 Hz, 3H), 7.26 - 7.15 (m, 2H), 6.90 (d, J = 8.4 Hz, 2H), 6.64 - 6.31 (m, 1H), 2.02 (s, 1H), 0.89 - 0.68 (m, 4H).
MS(ESI+) m/z 479 (M+H)+
실시예 29: N-(4-(4-(4-( 에틸술폰아미도 )-2- 메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-2- methylphenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00129
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.63 (s, 1H), 9.86 (s, 1H), 7.75 (s, 1H), 7.54 - 7.06 (m, 6H), 6.09 (s, 1H), 3.16 (q, J = 7.6 Hz, 3H), 2.14 (s, 3H), 2.04 (s, 1H), 1.23 (t, J = 7.5 Hz, 4H), 0.78 (d, J = 9.5 Hz, 4H).
MS(ESI+) m/z 399 (M+H)+
실시예 30: N-(4-(4-(4-( 에틸술폰아미도 )-2- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00130
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.63 (s, 1H), 10.26 (s, 1H), 7.94 (s, 1H), 7.56 (t, J = 8.4 Hz, 1H), 7.45 - 7.32 (m, 1H), 7.17 (d, J = 11.3 Hz, 2H), 6.38 - 6.26 (m, 1H), 3.23 (q, J = 7.2 Hz, 2H), 2.04 (s, 1H), 1.23 (t, J = 7.2 Hz, 3H), 0.92 - 0.71 (m, 4H).
MS(ESI+) m/z 403 (M+H)+
실시예 31: N-(4-(4-((4- 브로모 -3- 플루오로페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-bromo-3-fluorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00131
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.52 (s, 1H), 7.91 (s, 1H), 7.83 (t, J = 7.6 Hz, 1H), 7.65 (dd, J = 2.0, 8.5 Hz, 1H), 7.57 - 7.44 (m, 3H), 7.33 (t, J = 2.9 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H), 6.56 - 6.44 (m, 1H), 2.02 (s, 1H), 0.86 - 0.72 (m, 4H).
MS(ESI+) m/z 529, 531 (M+H)+
실시예 32: N-(4-(4-((4- 브로모 -2- 플루오로페닐 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-bromo-2-fluorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00132
1H NMR (400 MHz, DMSO-d6) δ 11.32 (s, 1H), 10.45 (s, 1H), 7.87 (s, 1H), 7.69 (t, J = 8.0 Hz, 1H), 7.54 - 7.42 (m, 1H), 7.42 - 7.24 (m, 4H), 6.96 - 6.82 (m, 2H), 6.57 - 6.42 (m, 1H), 2.00 (d, J = 12.5 Hz, 1H), 0.87 - 0.68 (m, 4H).
MS(ESI+) m/z 529, 531 (M+H)+
실시예 33: N-(4-(4-((4-클로로-3-(트리플루오로메틸)페닐)술폰아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드(N-(4-(4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00133
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.70 (s, 1H), 10.59 (s, 1H), 8.13 (d, J = 2.3 Hz, 1H), 8.10 - 8.03 (m, 1H), 7.96 (d, J = 7.7 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 7.49 - 7.35 (m, 1H), 7.27 (d, J = 8.3 Hz, 2H), 6.53 - 6.40 (m, 1H), 2.02 (d, J = 8.5 Hz, 1H), 0.85 - 0.70 (m, 4H).
MS(ESI+) m/z 535, 537 (M+H)+
실시예 34: N-(4-(4-(벤조[d][1,3]디옥솔-5-술폰아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드(N-(4-(4-(benzo[d][1,3]dioxole-5-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00134
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.59 (s, 1H), 10.40 (s, 1H), 7.94 (s, 1H), 7.61 (d, J = 8.3 Hz, 2H), 7.37 (dd, J = 5.7, 2.7 Hz, 2H), 7.27 (dd, J = 5.3, 3.2 Hz, 3H), 7.05 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.14 (s, 2H), 2.10 - 1.92 (m, 2H), 1.24 (s, 5H), 0.86 - 0.70 (m, 5H).
MS(ESI+) m/z 477 (M+H)+
실시예 35: N-(4-(4-(에틸설폰아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)-2-메틸시클로프로판-1-카복스아미드(N-(4-(4-(ethylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylcyclopropane-1-carboxamide)의 합성
Figure pat00135
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.59 (s, 1H), 10.02 (s, 1H), 7.96 (d, J = 5.8 Hz, 1H), 7.69 (dd, J = 4.1, 8.6 Hz, 2H), 7.47 (d, J = 7.8 Hz, 1H), 7.39 (dd, J = 4.4, 7.5 Hz, 3H), 7.11 (d, J = 7.9 Hz, 1H), 6.63 - 6.49 (m, 1H), 3.17 (q, J = 7.3 Hz, 2H), 1.86 - 1.74 (m, 1H), 1.34 - 1.17 (m, 5H), 1.17 - 0.93 (m, 4H).
MS(ESI+) m/z 399 (M+H)+
실시예 36: N-(4-(4-(((4-플루오로페닐)메틸)술폰아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드(N-(4-(4-(((4-fluorophenyl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00136
MS(ESI+) m/z 465 (M+H)+
실시예 37: N-(4-(4-((4-( N,N - 디메틸술파모일 )페닐) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-(N,N-dimethylsulfamoyl)phenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00137
MS(ESI+) m/z 540 (M+H)+
실시예 38: N-(4-(4-((2,3- 디히드로벤조[b][1,4]디옥신 )-6- 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((2,3-dihydrobenzo[b][1,4]dioxine)-6-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00138
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.58 (s, 1H), 7.94 (s, 1H), 7.60 (s, 2H), 7.27 (s, 5H), 7.01 (s, 2H), 6.49 (s, 1H), 4.28 (s, 4H), 2.03 (s, 1H), 0.80 (s, 4H).
MS(ESI+) m/z 491 (M+H)+
실시예 39: N-(4-(4-((4-(1H- 테트라졸 -1-일)페닐) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-(1H-tetrazol-1-yl)phenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00139
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.58 (s, 1H), 10.39 (s, 1H), 8.12 (d, J = 21.2 Hz, 1H), 7.94 (s, 1H), 7.74 (d, J = 8.7 Hz, 1H), 7.61 (t, J = 9.0 Hz, 2H), 7.39 - 7.00 (m, 6H), 6.48 (s, 1H), 2.03 (s, 1H), 0.80 (s, 4H).
MS(ESI+) m/z 501 (M+H)+
실시예 40: N-(4-(4-((6- 시아노피리딘 )-3- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((6- cyanopyridine )-3-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00140
1H NMR (400 MHz, DMSO-d6) δ 11.47 (d, J = 19.4 Hz, 1H), 10.56 (d, J = 12.4 Hz, 1H), 9.00 (d, J = 55.6 Hz, 1H), 8.46 - 7.81 (m, 4H), 7.56 (d, J = 37.7 Hz, 2H), 7.41 - 7.11 (m, 3H), 6.48 (d, J = 8.3 Hz, 1H), 2.02 (s, 1H), 0.79 (s, 4H).
MS(ESI+) m/z 459 (M+H)+
실시예 41: N-(4-(4-((1- 메틸에틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1- methylethyl ) sulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00141
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 9.96 (s, 1H), 7.99 (s, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 6.8 Hz, 3H), 6.54 (s, 1H), 2.04 (s, 1H), 1.30 - 1.24 (m, 6H), 0.81 (s, 4H).
MS(ESI+) m/z 399 (M+H)+
실시예 42: N-(4-(4-((1-에틸프로필) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1-ethylpropyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00142
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.62 (s, 1H), 10.04 (s, 1H), 7.99 (s, 1H), 7.70 - 7.62 (m, 2H), 7.41 - 7.34 (m, 3H), 6.54 (dd, J = 3.5, 1.8 Hz, 1H), 2.97 (dd, J = 8.7, 3.7 Hz, 1H), 2.03 (d, J = 5.0 Hz, 1H), 1.87 (ddd, J = 14.7, 7.6, 5.1 Hz, 2H), 1.70 (dt, J = 14.3, 7.2 Hz, 2H), 0.96 (t, J = 7.5 Hz, 6H), 0.80 (t, J = 5.5 Hz, 4H).
MS(ESI+) m/z 427 (M+H)+
실시예 43: N-(4-(4-((2- 메틸프로필 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2-methylpropyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00143
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 10.00 (s, 1H), 8.00 (s, 1H), 7.69 (d, J = 8.7 Hz, 2H), 7.37 (t, J = 9.9 Hz, 3H), 6.55 (s, 1H), 3.06 (d, J = 6.8 Hz, 2H), 2.17 (s, 1H), 2.04 (s, 1H), 1.05 - 0.95 (m, 6H), 0.81 (s, 4H).
MS(ESI+) m/z 413 (M+H)+
실시예 44: N-(4-(4-((2,2- 디메틸프로필 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2,2-dimethylpropyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00144
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 9.99 (s, 1H), 8.00 (s, 1H), 7.69 (d, J = 6.8 Hz, 2H), 7.44 - 7.29 (m, 3H), 6.55 (s, 1H), 3.11 (s, 2H), 2.04 (s, 1H), 1.11 (q, J = 7.5, 5.8 Hz, 9H), 0.81 (s, 4H).
MS(ESI+) m/z 427 (M+H)+
실시예 45: N-(4-(4-((3- 메틸부틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3- methylbutyl ) sulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00145
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 10.00 (s, 1H), 8.00 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 9.7 Hz, 3H), 6.53 (s, 1H), 3.14 (d, J = 8.8 Hz, 2H), 2.04 (s, 1H), 1.60 (s, 3H), 0.82 (s, 10H).
MS(ESI+) m/z 427 (M+H)+
실시예 46: N-(4-(4-(( 시클로프로필메틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((cyclopropylmethyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00146
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 10.06 (s, 1H), 7.99 (s, 1H), 7.74 - 7.61 (m, 2H), 7.38 (d, J = 8.9 Hz, 3H), 6.54 (s, 1H), 3.21 - 3.07 (m, 2H), 2.04 (s, 1H), 1.02 (s, 1H), 0.81 (s, 4H), 0.56 (s, 2H), 0.27 (s, 2H).
MS(ESI+) m/z 411 (M+H)+
실시예 47: N-(4-(4-((시클로헥실메틸)술폰아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드(N-(4-(4-((cyclohexylmethyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00147
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 10.01 (s, 1H), 8.00 (s, 1H), 7.68 (d, J = 7.9 Hz, 2H), 7.37 (t, J = 10.1 Hz, 3H), 6.54 (s, 1H), 3.11 - 2.99 (m, 2H), 2.03 (s, 1H), 1.85 (s, 2H), 1.63 (s, 2H), 1.24 (s, 2H), 1.06 (s, 2H), 0.81 (s, 4H).
MS(ESI+) m/z 453 (M+H)+
실시예 48: N-(4-(4-( 알릴술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-( allylsulfonamido ) phenyl )-1H- pyrrolo[2,3-b]pyridin -6-yl)cyclopropanecarboxamide)의 합성
Figure pat00148
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.63 (s, 1H), 10.12 (s, 1H), 8.00 (s, 1H), 7.69 (d, J = 8.3 Hz, 2H), 7.38 (dd, J = 8.2, 5.6 Hz, 3H), 6.55 (dd, J = 3.7, 1.9 Hz, 1H), 5.81 (ddd, J = 17.2, 10.1, 7.3 Hz, 1H), 5.36 (dd, J = 19.3, 13.6 Hz, 2H), 3.98 (d, J = 7.2 Hz, 2H), 2.04 (s, 1H), 0.85 - 0.76 (m, 4H).
MS(ESI+) m/z 397 (M+H)+
실시예 49: N-(4-(4-(( 플루오로메틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(( fluoromethyl ) sulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00149
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 2H), 8.00 (s, 1H), 7.69 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 11.9 Hz, 3H), 6.54 (s, 1H), 5.59 (s, 1H), 5.48 (s, 1H), 2.05 (s, 1H), 0.81 (s, 4H).
MS(ESI+) m/z 389 (M+H)+
실시예 50: N-(4-(4-(( 디플루오로메틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((difluoromethyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00150
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 11.16 (s, 1H), 10.62 (s, 1H), 8.01 (s, 1H), 7.72 (d, J = 8.6 Hz, 2H), 7.50 - 7.30 (m, 3H), 7.14 (d, J = 51.5 Hz, 1H), 6.53 (s, 1H), 2.05 (s, 1H), 0.92 - 0.71 (m, 4H).
MS(ESI+) m/z 407 (M+H)+
실시예 51: N-(4-(4-((2,2-디플루오로에틸)술폰아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로 프로판 카르복사미드 (N-(4-(4-((2,2-difluoroethyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00151
1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 10.48 (s, 1H), 7.92 (s, 1H), 7.44 (s, 2H), 7.32 (s, 1H), 6.70 (s, 2H), 6.54 (s, 1H), 5.40 (s, 2H), 4.03 (s, 1H), 2.03 (s, 1H), 0.79 (d, J = 14.6 Hz, 4H).
MS(ESI+) m/z 421 (M+H)+
실시예 52: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00152
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.60 (s, 1H), 10.22 - 9.95 (m, 1H), 8.00 (s, 1H), 7.70 (d, J = 8.1 Hz, 2H), 7.39 (s, 3H), 6.54 (s, 1H), 3.24 (d, J = 6.7 Hz, 2H), 2.67 (t, J = 7.4 Hz, 2H), 2.02 (d, J = 12.0 Hz, 3H), 0.81 (s, 4H).
MS(ESI+) m/z 424 (M+H)+
실시예 53: N-(4-(4-((2- 에톡시에틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2-ethoxyethyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00153
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 9.89 (s, 1H), 8.01 (d, J = 15.2 Hz, 1H), 7.68 (d, J = 8.9 Hz, 2H), 7.48 - 7.29 (m, 3H), 6.54 (s, 1H), 3.83 - 3.68 (m, 2H), 3.49 - 3.39 (m, 4H), 2.05 (s, 1H), 1.13 - 0.98 (m, 3H), 0.91 - 0.73 (m, 4H).
MS(ESI+) m/z 429 (M+H)+
실시예 54: N-(4-(4-(((테트라히드로푸란-3-일) 메틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6- 일) 시클로프로판카르복사미드 (N-(4-(4-(((tetrahydrofuran-3-yl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00154
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 1H), 9.93 (s, 1H), 8.00 (s, 1H), 7.80 - 7.63 (m, 2H), 7.38 (d, J = 11.3 Hz, 3H), 6.55 (s, 1H), 3.89 (d, J = 10.3 Hz, 1H), 3.66 (d, J = 29.1 Hz, 2H), 2.09 (d, J = 20.8 Hz, 2H), 1.64 (d, J = 12.5 Hz, 1H), 0.82 (s, 4H).
MS(ESI+) m/z 441 (M+H)+
실시예 55: N-(4-(4-((( 테트라히드로 -2H-피란-4-일) 메틸 ) 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((tetrahydro-2H-pyran-4-yl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00155
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.62 (d, J = 12.6 Hz, 1H), 9.93 (s, 1H), 8.00 (s, 1H), 7.68 (d, J = 9.5 Hz, 2H), 7.51 - 7.22 (m, 3H), 6.55 (d, J = 11.0 Hz, 1H), 3.81 (s, 2H), 3.14 (q, J = 6.7 Hz, 2H), 2.09 (d, J = 30.9 Hz, 2H), 1.76 (s, 2H), 1.32 (s, 2H), 0.82 (s, 4H).
MS(ESI+) m/z 455 (M+H)+
실시예 56: N-(4-(4-((2-( 메틸술포닐 )에틸) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2-(methylsulfonyl)ethyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00156
MS(ESI+) m/z 463 (M+H)+
실시예 57: N-(4-(4-( 시클로프로판술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclopropanesulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00157
1H NMR (400 MHz, DMSO-d 6) δ 11.51 (s, 1H), 10.60 (s, 1H), 9.94 (s, 1H), 8.00 (s, 1H), 7.68 (dd, J = 11.1, 4.7 Hz, 2H), 7.40 (d, J = 8.1 Hz, 3H), 6.54 (s, 1H), 2.71 (s, 1H), 2.04 (s, 1H), 0.97 (d, J = 9.6 Hz, 4H), 0.80 (d, J = 12.4 Hz, 4H).
MS(ESI+) m/z 397 (M+H)+
실시예 58: N-(4-(4-( 시클로부탄술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclobutanesulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00158
1H NMR (400 MHz, DMSO-d 6) δ 11.53 (s, 1H), 10.62 (s, 1H), 9.93 (s, 1H), 7.99 (s, 1H), 7.70 - 7.64 (m, 2H), 7.39 (dd, J = 3.5, 2.5 Hz, 1H), 7.35 (d, J = 8.6 Hz, 2H), 6.53 (dd, J = 3.6, 1.9 Hz, 1H), 3.99 (p, J = 8.0 Hz, 1H), 2.32 (d, J = 18.7 Hz, 2H), 2.20 (dt, J = 8.4, 4.4 Hz, 2H), 2.02 (d, J = 13.0 Hz, 1H), 1.95 - 1.82 (m, 2H), 0.81 (d, J = 4.4 Hz, 4H).
MS(ESI+) m/z 411 (M+H)+
실시예 59: N-(4-(3- 시아노 -4-( 에틸술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3- cyano -4-( ethylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00159
MS(ESI+) m/z 410 (M+H)+
실시예 60: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1- 메틸 -1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(ethylsulfonamido)-3-fluorophenyl)-1-methyl-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00160
1H NMR (400 MHz, DMSO-d 6) δ 10.77 (d, J = 19.2 Hz, 1H), 8.06 (d, J = 14.7 Hz, 1H), 7.69 - 7.46 (m, 4H), 6.57 (dd, J = 3.7, 1.8 Hz, 1H), 3.82 (d, J = 4.9 Hz, 3H), 2.08 (s, 1H), 1.27 (dt, J = 18.9, 7.1 Hz, 5H), 0.86 - 0.80 (m, 4H).
MS(ESI+) m/z 417 (M+H)+
실시예 61: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1-프로필-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-(ethylsulfonamido)-3-fluorophenyl)-1-propyl-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00161
1H NMR (400 MHz, DMSO-d 6) δ 10.72 (s, 1H), 8.07 (s, 1H), 7.68 - 7.50 (m, 4H), 6.59 (d, J = 3.6 Hz, 1H), 4.20 (t, J = 7.3 Hz, 2H), 3.60 (t, J = 7.0 Hz, 3H), 2.10 (s, 1H), 1.84 (q, J = 7.2 Hz, 2H), 1.42 (q, J = 7.5 Hz, 2H), 1.31 - 1.27 (m, 3H), 0.84 - 0.78 (m, 4H).
MS(ESI+) m/z 445 (M+H)+
실시예 62: N-(1-( 시아노메틸 )-4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(1-(cyanomethyl)-4-(4-(ethylsulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00162
1H NMR (400 MHz, DMSO-d 6) δ 10.88 (d, J = 15.7 Hz, 1H), 9.86 (s, 1H), 8.14 (d, J = 12.2 Hz, 1H), 7.70 - 7.48 (m, 4H), 6.70 (d, J = 3.8 Hz, 1H), 5.43 (d, J = 4.2 Hz, 2H), 2.12 (s, 1H), 1.28 (d, J = 6.7 Hz, 3H), 1.23 (s, 2H), 0.85 - 0.81 (m, 4H).
MS(ESI+) m/z 442 (M+H)+
실시예 63: N-(4-(3- 클로로 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-chloro-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00163
1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 10.70 (s, 1H), 9.65 (s, 1H), 8.02 (s, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.70 (dd, J = 2.0, 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.45 (dd, J = 2.5, 3.6 Hz, 1H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 3.20 - 3.12 (m, 2H), 2.03 (q, J = 5.9, 7.3 Hz, 1H), 1.84 - 1.74 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.85 - 0.75 (m, 4H).
MS(ESI+) m/z 433, 435 (M+H)+
실시예 64: N-(4-(4-( 에틸술폰아미도 )-3- 메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-3- methylphenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00164
1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 10.65 (s, 1H), 9.21 (s, 1H), 8.00 (s, 1H), 7.58 - 7.50 (m, 2H), 7.50 - 7.38 (m, 2H), 6.54 (dd, J = 1.9, 3.5 Hz, 1H), 3.15 (q, J = 7.3 Hz, 2H), 2.41 (s, 3H), 2.08 - 1.97 (m, 1H), 1.28 (t, J = 7.3 Hz, 3H), 0.89 - 0.74 (m, 4H).
MS(ESI+) m/z 399 (M+H)+
실시예 65: N-(4-(3- 메틸 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00165
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.64 (s, 1H), 9.11 (s, 1H), 8.00 (s, 1H), 7.58 - 7.50 (m, 2H), 7.47 - 7.37 (m, 2H), 6.54 (dd, J = 1.9, 3.5 Hz, 1H), 3.16 - 3.06 (m, 2H), 2.39 (s, 3H), 2.09 - 1.99 (m, 1H), 1.76 (q, J = 7.5 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.87 - 0.75 (m, 4H).
MS(ESI+) m/z 413 (M+H)+
실시예 66: N-(4-(3- 플루오로 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00166
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.68 (s, 1H), 9.84 (s, 1H), 8.02 (s, 1H), 7.62 - 7.52 (m, 3H), 7.49 - 7.40 (m, 1H), 6.56 (dd, J = 3.5, 1.8 Hz, 1H), 3.23 - 3.10 (m, 2H), 2.08 - 1.97 (m, 1H), 1.84 - 1.71 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.80 (dd, J = 10.1, 3.5 Hz, 4H).
MS(ESI+) m/z 417 (M+H)+
실시예 67: N-(4-(4-( 부틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( butylsulfonamido )-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00167
1H NMR (400 MHz, Chloroform-d) δ 11.59 (s, 1H), 10.65 (s, 1H), 9.82 (s, 1H), 8.02 (s, 1H), 7.62 - 7.53 (m, 3H), 7.43 (t, J = 3.0 Hz, 1H), 6.56 (dd, J = 3.5, 1.8 Hz, 1H), 3.21 - 3.13 (m, 2H), 2.11 - 1.98 (m, 1H), 1.73 (p, J = 7.7 Hz, 2H), 1.41 (q, J = 7.4 Hz, 2H), 0.89 (d, J = 7.3 Hz, 3H), 0.83 - 0.76 (m, 4H).
MS(ESI+) m/z 431 (M+H)+
실시예 68: N-(4-(4-( 시클로헥산술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일시클로프로판카르복사미드 (N-(4-(4-(cyclohexanesulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00168
1H NMR (400 MHz, Chloroform-d) δ 11.59 (s, 1H), 10.65 (s, 1H), 9.78 (s, 1H), 8.02 (s, 1H), 7.60 (t, J = 8.4 Hz, 1H), 7.54 (dd, J = 8.7, 4.7 Hz, 2H), 7.43 (d, J = 5.8 Hz, 1H), 6.56 (dd, J = 3.4, 1.7 Hz, 1H), 3.06 (t, J = 11.8 Hz, 1H), 2.12 (d, J = 12.3 Hz, 2H), 2.05 (s, 1H), 1.79 (d, J = 12.7 Hz, 2H), 1.62 (d, J = 13.0 Hz, 1H), 1.44 (q, J = 12.4 Hz, 2H), 1.34 - 1.25 (m, 2H), 1.15 (t, J = 12.7 Hz, 1H), 0.84 - 0.77 (m, 4H).
MS(ESI+) m/z 457 (M+H)+
실시예 69: N-(4-(4-( 시클로프로판술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(cyclopropanesulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00169
1H NMR (400 MHz, Chloroform-d) δ 11.59 (s, 1H), 10.65 (s, 1H), 9.80 (s, 1H), 8.01 (s, 1H), 7.58 (dt, J = 11.8, 6.9 Hz, 3H), 7.43 (d, J = 5.9 Hz, 1H), 6.56 (dd, J = 3.5, 1.8 Hz, 1H), 2.74 (td, J = 7.8, 3.8 Hz, 1H), 2.08 - 1.98 (m, 1H), 1.01 - 0.93 (m, 4H), 0.83 - 0.79 (m, 4H).
MS(ESI+) m/z 415 (M+H)+
실시예 70: N-(4-(4-(( 시클로헥실메틸 ) 술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((cyclohexylmethyl)sulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00170
1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.69 (s, 1H), 9.87 (s, 1H), 8.02 (s, 1H), 7.60 - 7.52 (m, 3H), 7.44 (t, J = 3.1 Hz, 1H), 6.56 (dd, J = 3.6, 1.8 Hz, 1H), 3.07 (d, J = 6.0 Hz, 2H), 2.04 (s, 1H), 1.89 (t, J = 14.8 Hz, 3H), 1.62 (dd, J = 27.0, 12.4 Hz, 3H), 1.30 - 0.97 (m, 7H), 0.86 - 0.75 (m, 4H)
MS(ESI+) m/z 471 (M+H)+
실시예 71: N-(4-(4-( 알릴술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( allylsulfonamido )-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00171
1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.69 (s, 1H), 9.92 (s, 1H), 8.02 (s, 1H), 7.58 (dd, J = 16.4, 8.0 Hz, 3H), 7.44 (t, J = 2.9 Hz, 1H), 6.56 (d, J = 4.7 Hz, 1H), 5.86 (td, J = 17.1, 7.2 Hz, 1H), 5.50 - 5.37 (m, 2H), 3.99 (d, J = 7.2 Hz, 2H), 2.06 - 1.99 (m, 1H), 0.81 (d, J = 4.8 Hz, 4H)
MS(ESI+) m/z 415 (M+H)+
실시예 72: N-(4-(3- 플루오로 -4-(((테트라히드로푸란-3-일) 메틸 ) 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-(((tetrahydrofuran-3-yl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00172
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.68 (s, 1H), 9.96 (s, 1H), 8.02 (s, 1H), 7.64 - 7.52 (m, 3H), 7.44 (dd, J = 3.5, 2.5 Hz, 1H), 6.56 (dd, J = 3.6, 1.8 Hz, 1H), 3.88 (dd, J = 8.6, 7.2 Hz, 1H), 3.72 (td, J = 8.3, 5.0 Hz, 1H), 3.63 (d, J = 7.8 Hz, 1H), 2.70 - 2.61 (m, 1H), 2.17 - 2.07 (m, 1H), 2.06 - 1.97 (m, 1H), 1.68 (dq, J = 12.3, 7.7 Hz, 1H), 0.83 - 0.78 (m, 4H)
MS(ESI+) m/z 459 (M+H)+
실시예 73: N-(4-(3- 플루오로 -4-((( 테트라히드로 -2H-피란-4-일) 메틸 ) 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-(((tetrahydro-2H-pyran-4-yl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00173
1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.69 (s, 1H), 9.91 (s, 1H), 8.03 (s, 1H), 7.62 - 7.53 (m, 3H), 7.46 - 7.41 (m, 1H), 6.56 (dd, J = 3.5, 1.8 Hz, 1H), 3.85 - 3.76 (m, 2H), 3.28 (dd, J = 11.7, 2.0 Hz, 2H), 3.16 (d, J = 6.4 Hz, 2H), 2.18 (q, J = 6.0, 4.1 Hz, 1H), 2.03 (d, J = 8.7 Hz, 1H), 1.78 (d, J = 13.0 Hz, 2H), 1.35 (qd, J = 12.2, 4.4 Hz, 2H), 0.84 - 0.75 (m, 4H)
MS(ESI+) m/z 473 (M+H)+
실시예 74: N-(4-(4-( 에틸술폰아미도 )페닐)-2- 메틸 -1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido ) phenyl )-2- methyl -1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00174
MS(ESI+) m/z 399 (M+H)+
실시예 75: N-(4-(3- 플루오로 -4-((2- 메틸프로필 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-((2-methylpropyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00175
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.68 (s, 1H), 8.02 (s, 1H), 7.62 - 7.50 (m, 3H), 7.44 (dd, J = 3.5, 2.5 Hz, 1H), 6.56 (dd, J = 3.5, 1.8 Hz, 1H), 3.08 (d, J = 6.4 Hz, 2H), 2.21 (dq, J = 13.3, 6.6 Hz, 1H), 2.04 (h, J = 6.2, 5.4 Hz, 1H), 1.04 (d, J = 6.7 Hz, 6H), 0.83 - 0.78 (m, 4H)
MS(ESI+) m/z 431 (M+H)+
실시예 76: N-(4-(3- 플루오로 -4-((3- 플루오로프로필 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-((3-fluoropropyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00176
1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.68 (s, 1H), 9.98 (s, 1H), 8.02 (s, 1H), 7.61 - 7.54 (m, 3H), 7.44 (t, J = 3.0 Hz, 1H), 6.56 (dd, J = 3.6, 1.8 Hz, 1H), 4.62 (t, J = 5.9 Hz, 1H), 4.50 (t, J = 6.0 Hz, 1H), 3.28 (d, J = 15.4 Hz, 2H), 2.12 (ddd, J = 33.0, 16.5, 9.7 Hz, 3H), 0.83 - 0.78 (m, 4H)
MS(ESI+) m/z 435 (M+H)+
실시예 77: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00177
1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.68 (s, 1H), 10.03 (s, 1H), 8.02 (s, 1H), 7.61 - 7.55 (m, 3H), 7.44 (dd, J = 3.5, 2.5 Hz, 1H), 6.56 (dd, J = 3.5, 1.8 Hz, 1H), 3.30 - 3.24 (m, 2H), 2.70 (t, J = 7.3 Hz, 2H), 2.06 (p, J = 7.2 Hz, 3H), 0.85 - 0.77 (m, 4H)
MS(ESI+) m/z 442 (M+H)+
실시예 78: N-(4-(4-( 시클로부탄술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(cyclobutanesulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00178
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.68 (s, 1H), 9.77 (s, 1H), 8.02 (s, 1H), 7.62 - 7.50 (m, 3H), 7.44 (t, J = 3.0 Hz, 1H), 6.55 (t, J = 2.5 Hz, 1H), 4.00 (t, J = 8.1 Hz, 1H), 2.42 - 1.82 (m, 6H), 0.81 (t, J = 6.5 Hz, 4H)
MS(ESI+) m/z 429 (M+H)+
실시예 79: N-(4-(4-((2,2- 디메틸프로필 ) 술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2,2-dimethylpropyl)sulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00179
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.68 (s, 1H), 8.02 (s, 1H), 7.62 - 7.51 (m, 3H), 7.44 (t, J = 2.8 Hz, 1H), 6.57 (s, 1H), 3.14 (s, 2H), 2.03 (d, J = 12.4 Hz, 1H), 1.11 (s, 9H), 0.81 (d, J = 4.6 Hz, 4H)
MS(ESI+) m/z 445 (M+H)+
실시예 80: N-(4-(4-(( 시클로프로필메틸 ) 술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((cyclopropylmethyl)sulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00180
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.67 (s, 1H), 9.88 (s, 1H), 8.01 (s, 1H), 7.60 (t, J = 8.4 Hz, 1H), 7.53 (t, J = 8.4 Hz, 2H), 7.43 (t, J = 3.0 Hz, 1H), 6.56 (d, J = 3.2 Hz, 1H), 3.14 (d, J = 7.0 Hz, 2H), 2.04 (s, 1H), 1.08 (s, 1H), 0.87 - 0.74 (m, 4H), 0.56 (q, J = 5.8 Hz, 2H), 0.34 (q, J = 5.1 Hz, 2H)
MS(ESI+) m/z 429 (M+H)+
실시예 81: N-(4-(4-( 에틸술폰아미도 )-3,5- 디플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-3,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00181
1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 10.73 (s, 1H), 9.64 (s, 1H), 8.03 (s, 1H), 7.53 - 7.42 (m, 3H), 6.58 (dd, J = 1.8, 3.5 Hz, 1H), 3.19 (q, J = 7.4 Hz, 2H), 2.09 - 1.99 (m, 1H), 1.34 (t, J = 7.3 Hz, 3H), 0.83 - 0.77 (m, 4H)
MS(ESI+) m/z 421 (M+H)+
실시예 82: N-(4-(3,5- 디플루오로 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3,5-difluoro-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00182
1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 10.73 (s, 1H), 9.64 (s, 1H), 8.03 (s, 1H), 7.51 - 7.45 (m, 3H), 6.58 (dd, J = 1.8, 3.6 Hz, 1H), 3.21 - 3.12 (m, 2H), 2.04 (dd, J = 5.7, 11.3 Hz, 1H), 1.83 (q, J = 7.6 Hz, 2H), 1.02 (t, J = 7.4 Hz, 3H), 0.86 - 0.78 (m, 4H).
MS(ESI+) m/z 435 (M+H)+
실시예 83: N-(4-(4-( 에틸술폰아미도 )-2,5- 디플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-2,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00183
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.69 (s, 1H), 10.12 (s, 1H), 7.96 (s, 1H), 7.54 - 7.46 (m, 1H), 7.45 - 7.38 (m, 2H), 6.32 (d, J = 2.1 Hz, 1H), 3.23 (q, J = 7.3 Hz, 2H), 2.03 (d, J = 5.8 Hz, 1H), 1.26 (q, J = 7.8, 8.3 Hz, 4H), 0.84 - 0.75 (m, 4H)
MS(ESI+) m/z 421 (M+H)+
실시예 84: N-(4-(2,5- 디플루오로 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2,5-difluoro-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00184
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.70 (s, 1H), 10.12 (s, 1H), 7.97 (s, 1H), 7.50 (dd, J = 6.7, 10.6 Hz, 1H), 7.46 - 7.37 (m, 2H), 6.32 (d, J = 2.6 Hz, 1H), 3.25 - 3.17 (m, 2H), 2.09 - 1.98 (m, 1H), 1.75 (dt, J = 7.6, 15.2 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.85 - 0.78 (m, 4H)
MS(ESI+) m/z 435 (M+H)+
실시예 85: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-3- 플루오로페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00185
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.67 (s, 1H), 10.18 (s, 1H), 8.01 (s, 1H), 7.56 (d, J = 13.3 Hz, 3H), 7.43 (s, 1H), 6.55 (s, 1H), 2.02 (s, 1H), 1.33 (d, J = 42.9 Hz, 2H), 1.23 (s, 2H), 0.81 (s, 4H)
MS(ESI+) m/z 454 (M+H)+
실시예 86: N-(4-(4-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 ) 술폰아미도 )-3- 플루오로페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00186
MS(ESI+) m/z 468 (M+H)+
실시예 87: N-(4-(4-((3- 시아노 -3- 메틸부틸 ) 술폰아미도 )-3- 플루오로페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyano-3-methylbutyl)sulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00187
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.68 (s, 1H), 10.03 (s, 1H), 8.02 (s, 1H), 7.57 (t, J = 5.9 Hz, 3H), 7.44 (s, 1H), 6.59 - 6.49 (m, 1H), 2.06 (d, J = 12.8 Hz, 5H), 1.23 (s, 6H), 0.85 - 0.77 (m, 4H)
MS(ESI+) m/z 470 (M+H)+
실시예 88: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00188
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.62 (s, 1H), 7.99 (s, 1H), 7.68 (d, J = 8.5 Hz, 2H), 7.41 - 7.32 (m, 3H), 6.53 (dd, J = 3.5, 1.8 Hz, 1H), 3.54 (s, 2H), 2.06 - 1.94 (m, 2H), 1.36 (q, J = 4.9 Hz, 2H), 1.20 - 1.14 (m, 2H), 0.83 - 0.75 (m, 4H)
MS(ESI+) m/z 436 (M+H)+
실시예 89: N-(4-(4-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 ) 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00189
1H NMR (400 MHz, Methanol-d4) δ 11.52 (s, 1H), 10.62 (s, 1H), 10.23 (s, 1H), 7.99 (s, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.42 - 7.31 (m, 3H), 6.54 (dd, J = 3.6, 1.8 Hz, 1H), 3.30 (s, 2H), 2.86 (s, 2H), 2.09 - 1.92 (m, 1H), 0.80 (td, J = 7.9, 2.9 Hz, 4H), 0.75 - 0.63 (m, 4H)
MS(ESI+) m/z 450 (M+H)+
실시예 90: N-(4-(4-( 시클로프로판술폰아미도 )-2- 메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclopropanesulfonamido )-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00190
1H NMR (400 MHz, Chloroform-d) δ 11.47 (s, 1H), 10.62 (s, 1H), 9.80 (s, 1H), 7.77 (s, 1H), 7.33 (dd, J = 3.5, 2.4 Hz, 1H), 7.26 - 7.15 (m, 3H), 6.08 (dd, J = 3.5, 1.9 Hz, 1H), 2.15 (s, 3H), 2.06 - 2.00 (m, 1H), 0.99 - 0.96 (m, 4H), 0.82 -0.74 (m, 4H)
MS(ESI+) m/z 411 (M+H)+
실시예 91: N-(4-(4-( 시클로부탄술폰아미도 )-2- 메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclobutanesulfonamido )-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00191
1H NMR (400 MHz, Chloroform-d) δ 11.47 (s, 1H), 10.62 (s, 1H), 9.77 (s, 1H), 7.76 (s, 1H), 7.33 (dd, J = 3.5, 2.5 Hz, 1H), 7.25 - 7.09 (m, 3H), 6.07 (dd, J = 3.5, 1.9 Hz, 1H), 3.99 (p, J = 8.1 Hz, 1H), 2.36 (dd, J = 19.7, 9.4 Hz, 2H), 2.23 - 2.17 (m, 2H), 2.13 (s, 3H), 2.03 (s, 1H), 1.95 - 1.84 (m, 2H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 425 (M+H)+
실시예 92: N-(4-(4-(( 시클로프로필메틸 ) 술폰아미도 )-2- 메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((cyclopropylmethyl)sulfonamido)-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00192
1H NMR (400 MHz, Chloroform-d) δ 11.47 (s, 1H), 10.61 (s, 1H), 9.91 (s, 1H), 7.76 (s, 1H), 7.33 (d, J = 2.4 Hz, 1H), 7.28 - 7.10 (m, 3H), 6.08 (dd, J = 3.5, 1.9 Hz, 1H), 3.13 (d, J = 7.1 Hz, 2H), 2.14 (s, 3H), 2.07 - 1.94 (m, 1H), 1.02 (td, J = 7.5, 3.8 Hz, 1H), 0.78 (dd, J = 8.4, 2.5 Hz, 4H), 0.58 - 0.53 (m, 2H), 0.28 (dt, J = 6.3, 4.5 Hz, 2H)
MS(ESI+) m/z 425 (M+H)+
실시예 93: N-(4-(4-( 에틸술폰아미도 )페닐)-3- 메틸 -1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido ) phenyl )-3- methyl -1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00193
1H NMR (400 MHz, Chloroform-d) δ 11.17 (s, 1H), 10.56 (s, 1H), 7.72 (s, 1H), 7.42 - 7.38 (m, 2H), 7.31 (d, J = 6.8 Hz, 2H), 7.10 (s, 1H), 3.15 (q, J = 7.2 Hz, 2H), 2.03 (s, 1H), 1.87 (s, 3H), 1.24 - 1.20 (m, 5H), 0.81 - 0.74 (m, 4H)
MS(ESI+) m/z 399 (M+H)+
실시예 94: N-(3- 메틸 -4-(4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(3-methyl-4-(4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00194
1H NMR (400 MHz, Chloroform-d) δ 11.17 (d, J = 2.4 Hz, 1H), 10.57 (s, 1H), 7.72 (s, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.34 - 7.28 (m, 3H), 7.10 (d, J = 2.1 Hz, 1H), 3.12 (t, J = 2.1 Hz, 2H), 2.02 (d, J = 2.1 Hz, 1H), 1.86 (s, 3H), 1.74 - 1.70 (m, 2H), 0.95 (d, J = 7.5 Hz, 3H), 0.81 - 0.73 (m, 4H)
MS(ESI+) m/z 413 (M+H)+
실시예 95: N-(4-(2- 메틸 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2-methyl-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00195
1H NMR (400 MHz, Chloroform-d) δ 11.48 (s, 1H), 10.62 (s, 1H), 9.84 (s, 1H), 7.77 (s, 1H), 7.33 (dd, J = 3.5, 2.5 Hz, 1H), 7.23 (s, 1H), 7.19 - 7.10 (m, 2H), 6.08 (dd, J = 3.5, 1.8 Hz, 1H), 3.16 - 3.11 (m, 2H), 2.14 (s, 3H), 2.09 - 2.01 (m, 1H), 1.72 (h, J = 7.5 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.83 - 0.73 (m, 4H)
MS(ESI+) m/z 413 (M+H)+
실시예 96: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 )-2- 메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00196
1H NMR (400 MHz, Chloroform-d) δ 11.47 (s, 1H), 10.62 (s, 1H), 7.76 (s, 1H), 7.37 - 7.31 (m, 1H), 7.24 (t, J = 7.1 Hz, 1H), 7.20 - 7.14 (m, 2H), 6.11 - 6.04 (m, 1H), 3.25 (dd, J = 8.5, 6.6 Hz, 2H), 2.68 (t, J = 7.3 Hz, 2H), 2.14 (s, 3H), 2.04 - 1.98 (m, 2H), 1.92 (d, J = 8.2 Hz, 1H), 0.82-0.74 (m, 4H)
MS(ESI+) m/z 438 (M+H)+
실시예 97: 6 -( 시클로프로판카르복사미도 )-4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H-피롤로[2,3-b]피리딘 7- 옥사이드 (6-( cyclopropanecarboxamido )-4-(4-(ethylsulfonamido)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridine 7- oxide )의 합성
Figure pat00197
1H NMR (400 MHz, DMSO-d6) δ 12.54 (s, 1H), 10.78 (s, 1H), 9.84 (s, 1H), 8.16 (s, 1H), 7.61 - 7.50 (m, 3H), 7.46 (t, J = 2.8 Hz, 1H), 6.71 (dd, J = 3.5, 1.8 Hz, 1H), 3.18 (q, J = 7.2 Hz, 2H), 2.41 (q, J = 6.5, 5.3 Hz, 1H), 1.28 (t, J = 7.3 Hz, 3H), 0.89 (d, J = 7.9 Hz, 4H)
MS(ESI+) m/z 419 (M+H)+
실시예 98: N-(4-(4-( 에틸술폰아미도 )-3-( 트리플루오로메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(ethylsulfonamido)-3-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00198
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.64 (s, 1H), 10.32 (s, 1H), 7.82 (s, 1H), 7.67 (d, J = 2.2 Hz, 1H), 7.60 - 7.52 (m, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.34 - 7.26 (m, 1H), 6.01 (dd, J = 3.6, 1.8 Hz, 1H), 3.24 (d, J = 7.4 Hz, 2H), 2.07 - 1.98 (m, 1H), 1.25 (t, J = 7.3 Hz, 3H), 0.81 - 0.72 (m, 4H)
MS(ESI+) m/z 453 (M+H)+
실시예 99: N-(4-(2-에틸-4-( 에틸술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2- ethyl -4-( ethylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00199
1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.61 (s, 1H), 9.85 (s, 1H), 7.77 (s, 1H), 7.32 (dd, J = 3.5, 2.4 Hz, 1H), 7.24 - 7.12 (m, 3H), 6.05 (dd, J = 3.5, 1.9 Hz, 1H), 3.16 (q, J = 7.3 Hz, 2H), 2.46 (d, J = 7.6 Hz, 2H), 2.11 - 1.97 (m, 1H), 1.23 (t, J = 7.3 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H), 0.81 - 0.72 (m, 4H)
MS(ESI+) m/z 413 (M+H)+
실시예 100: N-(4-(3- 플루오로 -2- 메틸 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-2-methyl-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00200
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.66 (s, 1H), 9.70 (s, 1H), 7.79 (s, 1H), 7.36 (dd, J = 5.4, 2.5 Hz, 2H), 7.12 (d, J = 8.4 Hz, 1H), 6.16 - 6.08 (m, 1H), 3.19 - 3.09 (m, 2H), 2.08 (d, J = 2.6 Hz, 3H), 2.05 - 2.01 (m, 1H), 1.83 - 1.73 (m, 2H), 1.00 (t, J = 7.2 Hz, 3H), 0.84 - 0.74 (m, 4H)
MS(ESI+) m/z 431 (M+H)+
실시예 101: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로 -2- 메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(ethylsulfonamido)-3-fluoro-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00201
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.66 (s, 1H), 9.71 (s, 1H), 7.79 (s, 1H), 7.40 - 7.30 (m, 2H), 7.18 - 7.06 (m, 1H), 6.11 (dd, J = 3.5, 1.9 Hz, 1H), 3.16 (t, J = 7.3 Hz, 2H), 2.08 (d, J = 2.7 Hz, 3H), 2.03 - 1.95 (m, 1H), 1.29 (t, J = 7.3 Hz, 3H), 0.82 - 0.73 (m, 4H)
MS(ESI+) m/z 417 (M+H)+
실시예 102: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-2- 메틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00202
1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.61 (s, 1H), 9.91 (s, 1H), 7.76 (s, 1H), 7.33 (dd, J = 3.5, 2.4 Hz, 1H), 7.23 (d, J = 8.3 Hz, 1H), 7.18 (d, J = 2.2 Hz, 1H), 7.14 (dd, J = 8.1, 2.3 Hz, 1H), 6.07 (dd, J = 3.5, 1.9 Hz, 1H), 3.52 (s, 2H), 2.14 (s, 3H), 1.99 (dt, J = 14.0, 7.8 Hz, 2H), 1.38 - 1.33 (m, 2H), 1.22 - 1.16 (m, 2H), 0.80 - 0.74 (m, 4H)
MS(ESI+) m/z 450 (M+H)+
실시예 103: N-(4-(4-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 ) 술폰아미도 )-2- 메틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonamido)-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00203
1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.61 (s, 1H), 7.76 (s, 1H), 7.32 (dd, J = 3.4, 2.4 Hz, 1H), 7.24 (d, J = 8.3 Hz, 1H), 7.17 - 7.11 (m, 2H), 2.86 (s, 2H), 2.14 (s, 3H), 2.05 - 1.95 (m, 2H), 0.79 (d, J = 3.8 Hz, 2H), 0.75 - 0.65 (m, 4H)
MS(ESI+) m/z 464 (M+H)+
실시예 104: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 )-2,5- 디플루오로페닐 )-1H-피롤로[2,3-b]피리딘 6-일) 시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)-2,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00204
1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 10.69 (s, 1H), 7.96 (d, J = 1.2 Hz, 1H), 7.52 (dd, J = 6.6, 10.6 Hz, 1H), 7.47 - 7.39 (m, 4H), 6.31 (dt, J = 2.0, 3.9 Hz, 1H), 3.37 (s, 2H), 2.70 (t, J = 7.3 Hz, 2H), 2.11 - 1.99 (m, 3H), 0.85 - 0.76 (m, 4H)
MS(ESI+) m/z 460 (M+H)+
실시예 105: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 ) -2,5- 디플루오로페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-2,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00205
1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 10.67 (s, 1H), 7.96 (s, 1H), 7.47 (ddd, J = 6.8, 11.0, 15.3 Hz, 2H), 7.40 (dd, J = 2.5, 3.5 Hz, 1H), 6.31 (dd, J = 1.9, 3.6 Hz, 1H), 3.62 (s, 2H), 2.07 - 2.00 (m, 1H), 1.38 (q, J = 4.1, 4.8 Hz, 2H), 1.30 - 1.22 (m, 2H), 0.84 - 0.75 (m, 4H)
MS(ESI+) m/z 472 (M+H)+
실시예 106: N-(4-(4-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 ) 술폰아미도 )-2,5-디플루오로페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonamido)-2,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00206
MS(ESI+) m/z 486 (M+H)+
실시예 107: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-3,5- 디플루오로페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-3,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00207
MS(ESI+) m/z 472 (M+H)+
실시예 108: N-(4-(4-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 ) 술폰아미도 )-3,5-디플루오로페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonamido)-3,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00208
1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 10.71 (s, 1H), 8.03 (s, 1H), 7.52 - 7.44 (m, 3H), 6.58 (dd, J = 1.8, 3.5 Hz, 1H), 3.38 (s, 2H), 2.86 (s, 2H), 2.04 (td, J = 3.8, 7.4, 7.8 Hz, 1H), 0.93 - 0.87 (m, 2H), 0.82 (ddd, J = 2.3, 6.2, 9.5 Hz, 4H), 0.74 - 0.68 (m, 2H)
MS(ESI+) m/z 486 (M+H)+
실시예 109: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-2- 에틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-2-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00209
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.63 (s, 1H), 10.23 (s, 1H), 7.77 (s, 1H), 7.32 (s, 1H), 7.25 - 7.09 (m, 3H), 6.04 (d, J = 3.2 Hz, 1H), 3.52 (s, 2H), 2.04 (d, J = 14.3 Hz, 1H), 1.36 (s, 2H), 1.20 (d, J = 5.2 Hz, 2H), 0.95 (t, J = 7.6 Hz, 3H), 0.77 (d, J = 7.3 Hz, 4H)
MS(ESI+) m/z 464 (M+H)+
실시예 110: N-(4-(4-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 ) 술폰아미도 )-2- 에틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonamido)-2-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00210
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.63 (s, 1H), 10.08 (s, 1H), 7.77 (s, 1H), 7.32 (s, 1H), 7.19 (d, J = 10.0 Hz, 2H), 7.12 (d, J = 8.6 Hz, 1H), 6.04 (s, 1H), 2.85 (s, 2H), 2.03 (s, 1H), 0.95 (t, J = 7.6 Hz, 3H), 0.78 (s, 4H), 0.73 (s, 2H), 0.66 (s, 2H)
MS(ESI+) m/z 478 (M+H)+
실시예 111: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 )-2- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)-2-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00211
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.64 (s, 1H), 10.01 (s, 1H), 7.78 (s, 1H), 7.32 (s, 1H), 7.18 (dd, J = 23.0, 9.1 Hz, 3H), 6.05 (s, 1H), 3.25 (t, J = 7.9 Hz, 2H), 2.68 (t, J = 7.3 Hz, 2H), 2.02 (q, J = 7.5 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H), 0.77 (d, J = 7.7 Hz, 4H)
MS(ESI+) m/z 452 (M+H)+
실시예 112: N-(4-(4-( 시클로헥산술폰아미도 )-2- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclohexanesulfonamido )-2-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00212
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.65 (s, 1H), 9.86 (d, J = 13.7 Hz, 1H), 7.79 (s, 1H), 7.41 - 7.07 (m, 4H), 6.05 (s, 1H), 3.06 (s, 1H), 2.06 (s, 3H), 1.77 (s, 2H), 1.59 (s, 1H), 1.34 (d, J = 77.0 Hz, 3H), 1.17 - 1.05 (m, 1H), 0.93 - 0.81 (m, 5H)
MS(ESI+) m/z 467 (M+H)+
실시예 113: N-(4-(4-( 시클로프로판술폰아미도 )-2- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclopropanesulfonamido )-2-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00213
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.64 (s, 1H), 9.82 (s, 1H), 7.78 (s, 1H), 7.32 (d, J = 3.1 Hz, 1H), 7.25 (s, 1H), 7.18 (s, 2H), 6.04 (d, J = 3.0 Hz, 1H), 3.38 (d, J = 6.4 Hz, 1H), 2.74 - 2.65 (m, 1H), 2.04 (d, J = 6.9 Hz, 1H), 1.09 (t, J = 7.2 Hz, 1H), 0.97 (d, J = 7.2 Hz, 7H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 425 (M+H)+
실시예 114: N-(4-(4-( 시클로부탄술폰아미도 )-2- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclobutanesulfonamido )-2-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00214
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.64 (s, 1H), 9.78 (s, 1H), 7.77 (s, 1H), 7.32 (s, 1H), 7.14 (dd, J = 24.3, 10.7 Hz, 3H), 6.04 (s, 1H), 4.06 - 3.91 (m, 1H), 2.46 (s, 2H), 2.39 - 2.30 (m, 2H), 2.20 (s, 2H), 2.07 - 1.98 (m, 1H), 1.93 (dd, J = 19.3, 10.2 Hz, 2H), 0.94 (t, J = 7.6 Hz, 3H), 0.82 - 0.73 (m, 4H)
MS(ESI+) m/z 439 (M+H)+
실시예 115: N-(4-(2-에틸-4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2- ethyl -4-( propylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00215
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.64 (s, 1H), 9.87 (s, 1H), 7.78 (s, 1H), 7.32 (s, 1H), 7.16 (dd, J = 22.3, 9.1 Hz, 3H), 6.05 (s, 1H), 3.13 (t, J = 7.4 Hz, 2H), 2.42 (s, 2H), 2.02 (d, J = 7.2 Hz, 1H), 1.72 (q, J = 7.7 Hz, 2H), 0.96 (q, J = 7.8, 7.1 Hz, 6H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 427 (M+H)+
실시예 116: N-(4-(4-( 부틸술폰아미도 )-2- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( butylsulfonamido )-2- ethylphenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00216
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.63 (s, 1H), 9.87 (s, 1H), 7.78 (s, 1H), 7.32 (d, J = 3.1 Hz, 1H), 7.16 (dd, J = 22.4, 9.6 Hz, 3H), 6.04 (d, J = 2.9 Hz, 1H), 3.14 (t, J = 7.9 Hz, 2H), 2.42 (t, J = 7.3 Hz, 2H), 2.04 (d, J = 5.7 Hz, 1H), 1.69 (q, J = 8.0 Hz, 2H), 1.38 (q, J = 7.6 Hz, 2H), 0.94 (q, J = 6.1, 4.6 Hz, 3H), 0.84 (t, J = 7.4 Hz, 3H), 0.81 - 0.75 (m, 4H)
MS(ESI+) m/z 441 (M+H)+
실시예 117: N-(4-(2- 메틸 -4-((4,4,4- 트리플루오로부틸 ) 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(2-methyl-4-((4,4,4-trifluorobutyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00217
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.64 (s, 1H), 7.77 (s, 1H), 7.38 - 7.29 (m, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.21 - 7.11 (m, 2H), 6.07 (dd, J = 1.8, 3.5 Hz, 1H), 3.28 (t, J = 7.7 Hz, 2H), 2.47 - 2.35 (m, 2H), 2.14 (s, 3H), 1.99 (d, J = 33.4 Hz, 1H), 1.91 (dd, J = 5.7, 8.6 Hz, 2H), 0.83 - 0.74 (m, 4H)
MS(ESI+) m/z 481 (M+H)+
실시예 118: N-(4-(4-( 시클로프로판술폰아미도 )-2-( 트리플루오로메틸 )페닐)-1H-피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-(cyclopropanesulfonamido)-2-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00218
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.67 (s, 1H), 10.30 (s, 1H), 7.83 (s, 1H), 7.69 (t, J = 1.7 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.33 (t, J = 2.6 Hz, 1H), 6.00 (dt, J = 3.4, 1.6 Hz, 1H), 2.80 (p, J = 6.5 Hz, 1H), 2.06 - 1.96 (m, 1H), 1.04 - 0.95 (m, 4H), 0.77 (d, J = 6.5 Hz, 4H)
MS(ESI+) m/z 465 (M+H)+
실시예 119: N-(4-(4-( 프로필술포닐아미도 )-2-( 트리플루오로메틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(propylsulfonamido)-2-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00219
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.67 (s, 1H), 10.34 (s, 1H), 7.83 (s, 1H), 7.65 (s, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 2.5 Hz, 1H), 6.04 - 5.98 (m, 1H), 3.22 (t, J = 7.6 Hz, 2H), 2.05 - 1.98 (m, 1H), 1.73 (q, J = 7.7 Hz, 2H), 1.02 - 0.91 (m, 3H), 0.77 (d, J = 6.4 Hz, 4H)
MS(ESI+) m/z 467 (M+H)+
실시예 120: N-(4-(4-(시클로부탄술폰아미도)-2-(트리플루오로메틸)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드(N-(4-(4-(cyclobutanesulfonamido)-2-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00220
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.67 (s, 1H), 10.26 (s, 1H), 7.82 (s, 1H), 7.65 (s, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.33 (d, J = 3.3 Hz, 1H), 6.00 (t, J = 2.2 Hz, 1H), 4.08 (p, J = 8.2 Hz, 1H), 2.35 (p, J = 9.7 Hz, 2H), 2.22 (s, 2H), 2.02 (d, J = 6.4 Hz, 1H), 1.98 - 1.83 (m, 2H), 0.77 (d, J = 6.3 Hz, 4H)
MS(ESI+) m/z 479 (M+H)+
실시예 121: N-(4-(4-((3,4- 디플루오로페닐 ) 술폰아미도 )-2-( 트리플루오로메틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3,4-difluorophenyl)sulfonamido)-2-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00221
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.63 (s, 1H), 7.84 (s, 1H), 7.76 (s, 1H), 7.67 (s, 2H), 7.46 (s, 1H), 7.30 (s, 3H), 5.93 (s, 1H), 2.01 (s, 1H), 0.77 (s, 4H)
MS(ESI+) m/z 537 (M+H)+
실시예 122: N-(4-(4-((3- 플루오로페닐 ) 술폰아미도 )-2-( 트리플루오로메틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3-fluorophenyl)sulfonamido)-2-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00222
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.97 (s, 1H), 10.65 (s, 1H), 7.76 (s, 1H), 7.68 (s, 2H), 7.63 (d, J = 8.6 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.53 (s, 1H), 7.46 (d, J = 8.6 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.31 (d, J = 3.2 Hz, 1H), 5.90 (s, 1H), 2.06 - 1.95 (m, 1H), 0.81-0.73 (m, 4H)
MS(ESI+) m/z 519 (M+H)+
실시예 123: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-3- 에틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-3-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00223
1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 10.64 (s, 1H), 9.47 (s, 1H), 8.01 (s, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.52 (dd, J = 8.3, 2.1 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.41 (t, J = 3.0 Hz, 1H), 6.52 (dd, J = 3.6, 1.8 Hz, 1H), 3.54 (s, 2H), 2.81 (q, J = 7.5 Hz, 2H), 2.09 - 1.98 (m, 1H), 1.40 (q, J = 4.8, 3.9 Hz, 2H), 1.29 (t, J = 3.7 Hz, 2H), 1.22 (t, J = 7.5 Hz, 3H), 0.86 - 0.73 (m, 4H)
MS(ESI+) m/z 464 (M+H)+
실시예 124: N-(4-(3-에틸-4-( 에틸술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3- ethyl -4-( ethylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00224
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.64 (s, 1H), 9.18 (s, 1H), 8.01 (s, 1H), 7.59 (d, J = 2.1 Hz, 1H), 7.53 (dd, J = 8.2, 2.1 Hz, 1H), 7.45 - 7.39 (m, 2H), 6.52 (dd, J = 3.5, 1.8 Hz, 1H), 3.17 (q, J = 7.3 Hz, 2H), 2.81 (q, J = 7.5 Hz, 2H), 2.04 (d, J = 7.0 Hz, 1H), 1.30 (t, J = 7.3 Hz, 3H), 1.22 (t, J = 7.5 Hz, 3H), 0.83 - 0.78 (m, 4H)
MS(ESI+) m/z 413 (M+H)+
실시예 125: N-(4-(4-( 시클로프로판술폰아미도 )-3- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclopropanesulfonamido )-3-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00225
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.64 (s, 1H), 9.22 (s, 1H), 8.02 (s, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.55 - 7.47 (m, 2H), 7.41 (dd, J = 3.5, 2.5 Hz, 1H), 6.53 (dd, J = 3.6, 1.9 Hz, 1H), 2.84 (q, J = 7.5 Hz, 2H), 2.72 - 2.67 (m, 1H), 2.03 (t, J = 6.5 Hz, 1H), 1.22 (t, J = 7.5 Hz, 3H), 1.03 - 0.95 (m, 2H), 0.94 - 0.89 (m, 2H), 0.84 - 0.76 (m, 4H)
MS(ESI+) m/z 425 (M+H)+
실시예 126: N-(4-(3-에틸-4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3- ethyl -4-( propylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00226
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.64 (s, 1H), 9.19 (s, 1H), 8.01 (s, 1H), 7.59 (d, J = 2.1 Hz, 1H), 7.55 - 7.50 (m, 1H), 7.46 - 7.38 (m, 2H), 6.53 (dd, J = 3.5, 1.8 Hz, 1H), 3.17 - 3.09 (m, 2H), 2.81 (q, J = 7.5 Hz, 2H), 2.04 (s, 1H), 1.78 (h, J = 7.4 Hz, 2H), 1.21 (t, J = 7.5 Hz, 3H), 1.01 (t, J = 7.5 Hz, 3H), 0.85 - 0.76 (m, 4H)
MS(ESI+) m/z 427 (M+H)+
실시예 127: N-(4-(4-( 부틸술폰아미도 )-3- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( butylsulfonamido )-3- ethylphenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00227
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.64 (s, 1H), 9.19 (s, 1H), 8.01 (s, 1H), 7.58 (d, J = 2.1 Hz, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.45 - 7.36 (m, 2H), 6.52 (dd, J = 3.5, 1.9 Hz, 1H), 3.18 - 3.12 (m, 2H), 2.81 (q, J = 7.5 Hz, 2H), 2.04 (s, 1H), 1.72 (q, J = 7.7 Hz, 2H), 1.43 (h, J = 7.3 Hz, 2H), 1.21 (t, J = 7.5 Hz, 3H), 0.89 (t, J = 7.4 Hz, 3H), 0.84 - 0.76 (m, 4H)
MS(ESI+) m/z 441 (M+H)+
실시예 128: N-(4-(4-( 시클로부탄술폰아미도 )-3- 에틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( cyclobutanesulfonamido )-3-ethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00228
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.64 (s, 1H), 9.15 (s, 1H), 8.01 (s, 1H), 7.57 (d, J = 2.0 Hz, 1H), 7.51 (dd, J = 8.2, 2.2 Hz, 1H), 7.44 - 7.34 (m, 2H), 6.52 (dd, J = 3.5, 1.8 Hz, 1H), 3.97 (p, J = 8.2 Hz, 1H), 2.79 (q, J = 7.5 Hz, 2H), 2.38 - 2.23 (m, 4H), 2.03 (d, J = 4.8 Hz, 1H), 1.97 - 1.86 (m, 2H), 1.21 (t, J = 7.5 Hz, 3H), 0.84 - 0.76 (m, 4H)
MS(ESI+) m/z 439 (M+H)+
실시예 129: N-(4-(6-( 메틸술폰아미도 )-[1,1'-비페닐]-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(6-( methylsulfonamido )-[1,1'-biphenyl]-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00229
1H NMR (400 MHz, DMSO-d6) δ 11.25 (s, 1H), 10.47 (d, J = 3.2 Hz, 1H), 10.04 (t, J = 2.8 Hz, 1H), 7.68 (d, J = 3.2 Hz, 1H), 7.42 - 7.28 (m, 3H), 7.17 - 7.04 (m, 6H), 5.86 (s, 1H), 3.22 (d, J = 6.5 Hz, 2H), 1.98 (d, J = 7.2 Hz, 1H), 1.25 (q, J = 7.0, 5.7 Hz, 3H), 0.74 (d, J = 5.9 Hz, 4H)
MS(ESI+) m/z 447 (M+H)+
실시예 130: N-(4-(6-( 시클로프로판술폰아미도 )-[1,1'-비페닐]-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(6-(cyclopropanesulfonamido)-[1,1'-biphenyl]-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00230
1H NMR (400 MHz, DMSO-d6) δ 11.25 (s, 1H), 10.48 (s, 1H), 9.98 (s, 1H), 7.69 (s, 1H), 7.41 - 7.30 (m, 3H), 7.19 - 7.07 (m, 6H), 5.85 (s, 1H), 2.78 (d, J = 7.9 Hz, 1H), 1.98 (d, J = 7.5 Hz, 1H), 1.01 (t, J = 4.6 Hz, 4H), 0.75 (d, J = 6.1 Hz, 4H)
MS(ESI+) m/z 473 (M+H)+
실시예 131: N-(4-(4-( 에틸술폰아미도 )-2,3- 디메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-2,3-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00231
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.63 (s, 1H), 9.15 (d, J = 4.1 Hz, 1H), 7.75 (d, J = 4.2 Hz, 1H), 7.33 (s, 1H), 7.28 - 7.00 (m, 2H), 6.04 (s, 1H), 3.11 (p, J = 7.4 Hz, 2H), 2.31 (t, J = 2.9 Hz, 3H), 2.07 (t, J = 2.9 Hz, 3H), 2.03 (s, 1H), 1.29 (dt, J = 11.0, 5.8 Hz, 3H), 0.77 (d, J = 8.2 Hz, 4H)
MS(ESI+) m/z 413 (M+H)+
실시예 132: N-(4-(2,3-디메틸-4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2,3-dimethyl-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00232
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.63 (s, 1H), 9.15 (d, J = 4.4 Hz, 1H), 7.76 (t, J = 3.2 Hz, 1H), 7.33 (s, 1H), 7.22 (d, J = 7.8 Hz, 1H), 7.10 (t, J = 6.4 Hz, 1H), 6.04 (s, 1H), 3.08 (q, J = 6.4, 4.8 Hz, 2H), 2.30 (d, J = 4.4 Hz, 3H), 2.06 (d, J = 4.1 Hz, 3H), 2.03 (s, 1H), 1.78 (q, J = 7.4 Hz, 2H), 1.01 (t, J = 7.0 Hz, 3H), 0.82 - 0.76 (m, 4H)
MS(ESI+) m/z 427 (M+H)+
실시예 133: N-(4-(4-( 시클로프로판술폰아미도 )-2,3- 디메틸페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(cyclopropanesulfonamido)-2,3-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00233
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.63 (d, J = 3.3 Hz, 1H), 9.18 (d, J = 3.1 Hz, 1H), 7.76 (d, J = 3.5 Hz, 1H), 7.33 (s, 1H), 7.25 (d, J = 4.5 Hz, 1H), 7.09 (d, J = 8.9 Hz, 1H), 6.03 (s, 1H), 2.64 (s, 1H), 2.34 (d, J = 2.9 Hz, 3H), 2.07 (d, J = 4.8 Hz, 3H), 0.93 (d, J = 29.3 Hz, 4H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 425 (M+H)+
실시예 134: 6 -( 시클로프로판카르복사미도 )-4-(4-( 에틸술폰아미도 )-2- 메틸페닐 )-1H-피롤로[2,3-b]피리딘 7- 옥사이드(6- ( cyclopropanecarboxamido )-4-(4-(ethylsulfonamido)-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridine 7- oxide )의 합성
Figure pat00234
MS(ESI+) m/z 415 (M+H)+
실시예 135: 6 -( 시클로프로판카르복사미도 )-4-(3-에틸-4-( 에틸술폰아미도 )페닐)-1H-피롤로[2,3-b] 피리딘 7- 옥사이드 (6-( cyclopropanecarboxamido )-4-(3-ethyl-4-(ethylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridine 7- oxide )의 합성
Figure pat00235
MS(ESI+) m/z 429 (M+H)+
실시예 136: 6 -( 시클로프로판카르복사미도 )-4-(4-( 시클로프로판술폰아미도 )-2,3-디메틸페닐)-1H-피롤로[2,3-b]피리딘 7- 옥사이드 (6-(cyclopropanecarboxamido)-4-(4-(cyclopropanesulfonamido)-2,3-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridine 7- oxide )의 합성
Figure pat00236
MS(ESI+) m/z 441 (M+H)+
실시예 137: 4 -(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-2- 에틸페닐 )-6-(시클로 프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 7- 옥사이드 4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-2-ethylphenyl)-6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridine 7- oxide의 합성
Figure pat00237
MS(ESI+) m/z 480 (M+H)+
실시예 138: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-3,5- 디에틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)-3,5-diethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00238
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 10.97 (s, 1H), 10.65 (s, 1H), 8.23 (s, 1H), 7.53 (s, 2H), 7.11 (d, J = 7.8 Hz, 1H), 6.58 - 6.47 (m, 1H), 3.06 (s, 2H), 2.60 (q, J = 7.5 Hz, 4H), 2.05 (s, 1H), 1.40 (d, J = 10.4 Hz, 4H), 1.19 (t, J = 7.5 Hz, 6H), 0.85 - 0.74 (m, 4H)
MS(ESI+) m/z 492 (M+H)+
실시예 139: N-(4-(4-((3,4- 디플루오로페닐 ) 술폰아미도 )-3,5- 디에틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3,4-difluorophenyl)sulfonamido)-3,5-diethylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00239
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.62 (s, 1H), 9.73 (s, 1H), 8.00 (s, 1H), 7.84 - 7.67 (m, 2H), 7.63 (d, J = 9.6 Hz, 1H), 7.41 (s, 3H), 6.48 (dd, J = 3.6, 1.9 Hz, 1H), 2.05 (d, J = 5.8 Hz, 1H), 1.05 (t, J = 7.5 Hz, 6H), 0.85 - 0.74 (m, 4H)
MS(ESI+) m/z 525 (M+H)+
실시예 140: 메틸2 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-5-(에틸술폰아미도)벤조에이트 ( methyl 2-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-(ethylsulfonamido)benzoate)의 합성
Figure pat00240
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.60 (s, 1H), 10.19 (s, 1H), 7.79 (s, 1H), 7.66 (s, 1H), 7.50 (s, 2H), 7.33 (s, 1H), 6.09 (s, 1H), 3.46 (s, 3H), 3.21 (q, J = 7.3 Hz, 2H), 2.04 (s, 1H), 1.23 (t, J = 7.3 Hz, 3H), 0.82 - 0.75 (m, 4H)
MS(ESI+) m/z 443 (M+H)+
실시예 141: 메틸2 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-5-(프로필술폰아미도)벤조에이트 ( methyl 2-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-(propylsulfonamido)benzoate)의 합성
Figure pat00241
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.60 (s, 1H), 10.19 (s, 1H), 7.79 (s, 1H), 7.65 (t, J = 1.5 Hz, 1H), 7.50 (d, J = 1.5 Hz, 2H), 7.33 (dd, J = 3.5, 2.4 Hz, 1H), 6.09 (dd, J = 3.6, 1.9 Hz, 1H), 3.46 (s, 3H), 3.23 - 3.10 (m, 2H), 2.08 - 1.99 (m, 1H), 1.78 - 1.61 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.83 - 0.72 (m, 4H)
MS(ESI+) m/z 457 (M+H)+
실시예 142: 메틸5 -(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-2-(6-( 시클로프로판카르복사미도 )-1H-피롤로[2,3-b]피리딘-4-일)벤조에이트 ( methyl 5-(((1-cyanocyclopropyl)methyl)sulfonamido)-2-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)benzoate)의 합성
Figure pat00242
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.60 (s, 1H), 7.79 (s, 1H), 7.66 (d, J = 1.5 Hz, 1H), 7.49 (d, J = 1.5 Hz, 2H), 7.32 (t, J = 3.0 Hz, 1H), 6.07 (dd, J = 3.5, 1.9 Hz, 1H), 3.59 (s, 2H), 3.45 (s, 3H), 2.03 (s, 1H), 1.37 (q, J = 4.8 Hz, 2H), 1.20 (q, J = 5.3, 4.9 Hz, 2H), 0.81 - 0.70 (m, 4H)
MS(ESI+) m/z 494 (M+H)+
실시예 143: 5 -(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )-2-(6-( 시클로프로판카르복사미도 )-1H-피롤로[2,3-b]피리딘-4-일)벤조산 (5-(((1-cyanocyclopropyl)methyl)sulfonamido)-2-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)benzoic acid )의 합성
Figure pat00243
MS(ESI+) m/z 480 (M+H)+
실시예 144: N-(4-(2- 시아노 -4-( 에틸술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2- cyano -4-( ethylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00244
1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 10.72 (s, 1H), 10.40 (s, 1H), 7.98 (s, 1H), 7.75 - 7.59 (m, 3H), 7.42 (t, J = 3.0 Hz, 1H), 6.27 (dd, J = 3.6, 1.8 Hz, 1H), 3.29 (q, J = 7.3 Hz, 2H), 2.10 - 1.98 (m, 1H), 1.25 (t, J = 7.3 Hz, 3H), 0.85 - 0.70 (m, 4H)
MS(ESI+) m/z 410 (M+H)+
실시예 145: N-(4-(2- 시아노 -4-( 프로필술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2-cyano-4-(propylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00245
1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 10.72 (s, 1H), 10.39 (s, 1H), 7.98 (s, 1H), 7.70 - 7.57 (m, 3H), 7.42 (t, J = 3.0 Hz, 1H), 6.27 (dd, J = 3.5, 1.7 Hz, 1H), 3.30 - 3.23 (m, 2H), 2.10 - 1.97 (m, 1H), 1.73 (h, J = 7.5 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.88 - 0.68 (m, 4H)
MS(ESI+) m/z 424 (M+H)+
실시예 146: N-(4-(2- 시아노 -4-((3,4- 디플루오로페닐 ) 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(2-cyano-4-((3,4-difluorophenyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00246
1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 11.04 (s, 1H), 10.71 (s, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H), 7.73 (d, J = 3.5 Hz, 1H), 7.72 - 7.67 (m, 1H), 7.64 - 7.60 (m, 2H), 7.54 (dd, J = 8.5, 2.3 Hz, 1H), 7.41 (t, J = 3.0 Hz, 1H), 6.20 (dd, J = 3.6, 1.8 Hz, 1H), 2.09 - 1.97 (m, 1H), 0.85 - 0.76 (m, 4H)
MS(ESI+) m/z 494 (M+H)+
실시예 147: N-(4-(2- 시아노 -4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(2-cyano-4-(((1-cyanocyclopropyl)methyl)sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00247
1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 10.78 (s, 1H), 10.72 (s, 1H), 7.98 (s, 1H), 7.70 - 7.57 (m, 3H), 7.42 (t, J = 3.0 Hz, 1H), 6.25 (t, J = 2.6 Hz, 1H), 3.70 (s, 2H), 2.09 - 1.98 (m, 1H), 1.09 (t, J = 7.0 Hz, 4H), 0.83 - 0.77 (m, 4H)
MS(ESI+) m/z 461 (M+H)+
실시예 148: N-(4-(6-( 에틸술폰아미도 )피리딘-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(6-( ethylsulfonamido ) pyridin -3- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00248
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.78 (s, 1H), 10.68 (s, 1H), 8.57 (s, 1H), 8.08 (dd, J = 2.5, 8.6 Hz, 1H), 8.01 (s, 1H), 7.43 (dd, J = 2.5, 3.5 Hz, 1H), 7.16 (d, J = 8.6 Hz, 1H), 6.54 (dd, J = 1.9, 3.5 Hz, 1H), 3.52 (s, 2H), 2.04 (t, J = 5.0 Hz, 1H), 1.25 (t, J = 7.3 Hz, 4H), 0.85 - 0.73 (m, 4H)
MS(ESI+) m/z 386 (M+H)+
실시예 149: N-(4-(5-( 에틸술폰아미도 )-6- 플루오로피리딘 -2-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(5-( ethylsulfonamido )-6-fluoropyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00249
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.67 (s, 1H), 8.39 (s, 1H), 8.01 (d, J = 9.7 Hz, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.47 (t, J = 3.0 Hz, 1H), 6.89 (dd, J = 1.9, 3.5 Hz, 1H), 3.20 (d, J = 7.4 Hz, 2H), 2.10 - 1.97 (m, 1H), 1.28 - 1.22 (m, 3H), 0.87 - 0.76 (m, 4H)
MS(ESI+) m/z 404 (M+H)+
실시예 150: N-(4-(6- 플루오로 -5-( 프로필술폰아미도 )피리딘-2-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(6-fluoro-5-(propylsulfonamido)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00250
1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.68 (s, 1H), 10.14 (s, 1H), 8.40 (s, 1H), 8.12 - 8.01 (m, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.48 (dd, J = 2.6, 3.5 Hz, 1H), 6.89 (dd, J = 1.9, 3.5 Hz, 1H), 3.26 - 3.16 (m, 2H), 2.04 (t, J = 3.9 Hz, 1H), 1.76 (h, J = 7.5 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.89 - 0.78 (m, 4H)
MS(ESI+) m/z 418 (M+H)+
실시예 151: N-(4-(4-( 에틸술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(ethylsulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00251
1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.83 (s, 1H), 7.31 (t, J = 3.0 Hz, 1H), 7.22 (d, J = 7.3 Hz, 1H), 6.50 (d, J = 3.4 Hz, 1H), 6.18 (s, 1H), 3.06 (q, J = 7.3 Hz, 2H), 2.24 (d, J = 9.8 Hz, 1H), 2.01 (s, 2H), 1.76 - 1.61 (m, 1H), 1.21 (d, J = 7.4 Hz, 3H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 389 (M+H)+
실시예 152: N-(4-(4-( 프로필설폰아마이드 ) 사이클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)사이클로프로판 카복스아미드 (N-(4-(4-(propylsulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00252
1H NMR (400 MHz, Chloroform-d) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.83 (s, 1H), 7.31 (t, J = 2.9 Hz, 1H), 7.21 (d, J = 7.4 Hz, 1H), 6.51 (dd, J = 1.8, 3.5 Hz, 1H), 6.18 (s, 1H), 3.11 - 2.99 (m, 2H), 2.22 (dd, J = 9.0, 17.2 Hz, 1H), 2.01 (s, 2H), 1.76 - 1.63 (m, 3H), 0.99 (t, J = 7.4 Hz, 3H), 0.81 - 0.72 (m, 4H)
MS(ESI+) m/z 403 (M+H)+
실시예 153: N-(4-(4-(( 트리플루오로메틸 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((trifluoromethyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00253
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.56 (s, 1H), 9.62 (d, J = 7.9 Hz, 1H), 7.82 (s, 1H), 7.32 (t, J = 3.0 Hz, 1H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 6.18 (s, 1H), 3.71 (s, 2H), 2.70 - 2.55 (m, 5H), 2.34 (d, J = 8.2 Hz, 1H), 2.02 (s, 2H), 1.82 (s, 1H), 0.84 - 0.76 (m, 4H)
MS(ESI+) m/z 429 (M+H)+
실시예 154: N-(4-(4-( 시클로프로판술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(cyclopropanesulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00254
1H NMR (400 MHz, Chloroform-d) δ 11.37 (s, 1H), 10.49 (s, 1H), 7.83 (s, 1H), 7.31 (dd, J = 2.4, 3.5 Hz, 1H), 7.22 (d, J = 7.5 Hz, 1H), 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 6.19 (s, 1H), 3.54 (d, J = 3.3 Hz, 1H), 2.68 - 2.55 (m, 4H), 2.30 - 2.19 (m, 1H), 2.08 (d, J = 13.3 Hz, 1H), 2.00 (dt, J = 4.8, 8.4 Hz, 1H), 1.72 (ddt, J = 5.7, 10.1, 15.5 Hz, 1H), 0.98 - 0.93 (m, 4H), 0.84 - 0.75 (m, 4H)
MS(ESI+) m/z 401 (M+H)+
실시예 155: N-(4-(4-((2- 시아노에틸 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((2-cyanoethyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00255
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 7.83 (s, 1H), 7.33 - 7.27 (m, 1H), 6.50 (dd, J = 1.4, 3.5 Hz, 1H), 6.18 (t, J = 3.4 Hz, 1H), 3.49 (q, J = 9.4, 10.2 Hz, 2H), 3.20 - 3.14 (m, 2H), 2.68 (t, J = 7.2 Hz, 2H), 2.58 (d, J = 18.9 Hz, 3H), 2.28 - 2.17 (m, 1H), 2.06 - 1.96 (m, 4H), 1.77 - 1.64 (m, 1H), 0.85 - 0.76 (m, 4H)
MS(ESI+) m/z 414 (M+H)+
실시예 156: N-(4-(4-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00256
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 7.83 (s, 1H), 7.39 (d, J = 6.9 Hz, 1H), 7.31 (dd, J = 2.5, 3.5 Hz, 1H), 6.50 (dd, J = 1.9, 3.5 Hz, 1H), 6.18 (s, 1H), 3.51 (s, 1H), 3.18 (s, 2H), 2.83 (s, 2H), 2.58 (d, J = 22.9 Hz, 3H), 2.23 (dd, J = 12.2, 23.6 Hz, 1H), 2.01 (s, 2H), 1.78 - 1.63 (m, 1H), 0.84 - 0.79 (m, 4H), 0.79 - 0.73 (m, 2H), 0.71- 0.65 (m, 2H)
MS(ESI+) m/z 454 (M+H)+
실시예 157: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00257
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 7.83 (s, 1H), 7.51 (s, 1H), 7.31 (dd, J = 2.5, 3.5 Hz, 1H), 6.50 (dd, J = 1.9, 3.5 Hz, 1H), 6.18 (s, 1H), 3.52 (d, J = 16.4 Hz, 1H), 3.37 (s, 2H), 2.59 (d, J = 29.8 Hz, 3H), 2.24 (dd, J = 9.4, 16.1 Hz, 1H), 2.12 - 1.97 (m, 2H), 1.78 - 1.63 (m, 1H), 1.36 (t, J = 3.5 Hz, 2H), 1.29 - 1.23 (m, 2H), 0.86 - 0.74 (m, 4H)
MS(ESI+) m/z 440 (M+H)+
실시예 158: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00258
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 7.83 (s, 1H), 7.40 (d, J = 6.4 Hz, 1H), 7.31 (dd, J = 2.4, 3.5 Hz, 1H), 6.50 (dd, J = 1.8, 3.5 Hz, 1H), 6.18 (s, 1H), 3.49 (s, 2H), 3.17 (dd, J = 6.4, 8.7 Hz, 2H), 2.68 (t, J = 7.3 Hz, 2H), 2.58 (d, J = 18.3 Hz, 3H), 2.23 (dd, J = 8.9, 17.2 Hz, 1H), 2.00 (h, J = 6.2, 7.3 Hz, 4H), 1.76 - 1.63 (m, 1H), 0.83 - 0.75 (m, 4H)
MS(ESI+) m/z 428 (M+H)+
실시예 159: N-(4-(4-((3- 플루오로프로필 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3-fluoropropyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00259
1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.83 (s, 1H), 7.36 (d, J = 7.3 Hz, 1H), 7.31 (dd, J = 2.5, 3.5 Hz, 1H), 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 6.18 (d, J = 4.3 Hz, 1H), 4.62 (t, J = 6.0 Hz, 1H), 4.51 (t, J = 6.0 Hz, 1H), 3.50 (s, 1H), 3.24 - 3.11 (m, 2H), 2.55 (s, 3H), 2.23 (dd, J = 8.8, 15.7 Hz, 1H), 2.13 - 1.98 (m, 4H), 1.71 (tt, J = 8.0, 15.8 Hz, 1H), 0.83 - 0.74 (m, 4H)
MS(ESI+) m/z 421 (M+H)+
실시예 160: N-(4-(4-( 알릴술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(allylsulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00260
1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.83 (d, J = 3.0 Hz, 1H), 7.34 - 7.26 (m, 2H), 6.50 (dt, J = 1.6, 3.2 Hz, 1H), 6.17 (s, 1H), 5.45 - 5.36 (m, 1H), 3.87 (d, J = 7.2 Hz, 1H), 2.57 (d, J = 23.0 Hz, 2H), 2.23 (d, J = 7.5 Hz, 1H), 2.01 (s, 2H), 1.87 (dd, J = 1.5, 6.7 Hz, 1H), 1.77 - 1.60 (m, 1H), 0.83 - 0.75 (m, 4H)
MS(ESI+) m/z 401 (M+H)+
실시예 161: N-(4-(4-(( 시클로프로필메틸 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((cyclopropylmethyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00261
1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.83 (s, 1H), 7.31 (dd, J = 2.3, 3.5 Hz, 1H), 7.21 (d, J = 6.1 Hz, 1H), 6.50 (dd, J = 1.6, 3.5 Hz, 1H), 6.18 (s, 1H), 3.51 (s, 1H), 3.01 (d, J = 6.9 Hz, 2H), 2.58 (d, J = 20.5 Hz, 3H), 2.23 (dd, J = 9.2, 16.8 Hz, 1H), 2.02 (s, 2H), 1.79 - 1.63 (m, 1H), 1.12 - 0.98 (m, 1H), 0.84 - 0.74 (m, 4H)
MS(ESI+) m/z 415 (M+H)+
실시예 162: N-(4-(4-((3,4- 디플루오로페닐 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3,4-difluorophenyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00262
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.51 (s, 1H), 7.92 (ddd, J = 2.2, 7.4, 9.8 Hz, 1H), 7.80 (s, 1H), 7.78 - 7.61 (m, 2H), 7.29 (dd, J = 2.2, 3.5 Hz, 1H), 6.47 (dd, J = 1.5, 3.5 Hz, 1H), 6.15 - 6.07 (m, 1H), 3.42 - 3.36 (m, 2H), 2.40 - 2.28 (m, 1H), 2.12 (ddd, J = 3.1, 8.3, 18.0 Hz, 1H), 2.00 (tt, J = 4.9, 7.8 Hz, 1H), 1.85 - 1.77 (m, 1H), 1.68 - 1.53 (m, 1H), 0.82 - 0.73 (m, 4H)
MS(ESI+) m/z 473 (M+H)+
실시예 163: N-(4-(4-((3- 플루오로페닐 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3-fluorophenyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00263
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.50 (s, 1H), 7.79 (s, 1H), 7.75 - 7.63 (m, 3H), 7.56 - 7.48 (m, 1H), 7.29 (dd, J = 2.2, 3.5 Hz, 1H), 6.47 (dd, J = 1.5, 3.5 Hz, 1H), 6.09 (d, J = 4.1 Hz, 1H), 2.49 (s, 3H), 2.39 - 2.25 (m, 1H), 2.12 (ddd, J = 3.0, 8.5, 18.1 Hz, 1H), 1.99 (dt, J = 4.9, 7.5 Hz, 1H), 1.83 - 1.73 (m, 1H), 1.69 - 1.54 (m, 1H), 0.77 (tdd, J = 4.0, 6.4, 9.9 Hz, 4H)
MS(ESI+) m/z 455 (M+H)+
실시예 164: N-(4-(4-((4- 시아노페닐 ) 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((4-cyanophenyl)sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00264
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.51 (s, 1H), 8.21 - 8.15 (m, 1H), 8.13 - 8.07 (m, 2H), 8.07 - 8.01 (m, 2H), 7.79 (s, 1H), 7.29 (dd, J = 2.5, 3.5 Hz, 1H), 6.47 (dd, J = 1.9, 3.5 Hz, 1H), 6.09 (t, J = 3.7 Hz, 1H), 3.40 (s, 2H), 3.17 (d, J = 3.2 Hz, 1H), 2.36 - 2.29 (m, 1H), 2.16 - 2.05 (m, 1H), 2.04 - 1.95 (m, 1H), 1.80 (d, J = 12.2 Hz, 1H), 1.63 (td, J = 5.8, 10.8, 11.7 Hz, 1H), 0.80 - 0.73 (m, 4H)
MS(ESI+) m/z 462 (M+H)+
실시예 165: N-(4-(4-( 시클로부탄술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(cyclobutanesulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00265
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.51 (s, 1H), 7.82 (s, 1H), 7.31 (dd, J = 2.5, 3.5 Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H), 6.50 (dd, J = 1.8, 3.5 Hz, 1H), 6.17 (s, 1H), 3.94 (p, J = 8.2 Hz, 1H), 3.65 - 3.54 (m, 1H), 2.37 - 2.14 (m, 5H), 2.06 - 1.80 (m, 4H), 1.69 (dd, J = 6.2, 11.5 Hz, 1H), 0.85 - 0.75 (m, 4H)
MS(ESI+) m/z 415 (M+H)+
실시예 166: N-(4-(1-( 에틸술포닐 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(ethylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00266
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 7.87 (s, 1H), 7.35 (t, J = 2.9 Hz, 1H), 6.57 (dd, J = 1.7, 3.6 Hz, 1H), 6.35 (d, J = 3.8 Hz, 1H), 4.00 (q, J = 2.9 Hz, 2H), 3.49 (t, J = 5.7 Hz, 4H), 3.14 (q, J = 7.3 Hz, 2H), 2.62 (s, 2H), 2.07 - 1.95 (m, 1H), 1.24 (t, J = 7.3 Hz, 3H), 0.84-0.77 (m, 4H)
MS(ESI+) m/z 375 (M+H)+
실시예 167: N-(4-(1-((3- 플루오로프로필 )술포닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-((3-fluoropropyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00267
MS(ESI+) m/z 407 (M+H)+
실시예 168: N-(4-(1-( 시클로프로필술포닐 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(cyclopropylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00268
MS(ESI+) m/z 387 (M+H)+
실시예 169: N-(4-(1-((( 테트라히드로 -2H-피란-4-일) 메틸 )술포닐)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(((tetrahydro-2H-pyran-4-yl)methyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00269
MS(ESI+) m/z 445 (M+H)+
실시예 170: N-(4-(1-((3-시아노프로필)술포닐)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드(N-(4-(1-((3-cyanopropyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00270
MS(ESI+) m/z 414 (M+H)+
실시예 171: N-(4-(1-(((1-( 시아노메틸 ) 시클로프로필 ) 메틸 )술포닐)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(((1-(cyanomethyl)cyclopropyl)methyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00271
MS(ESI+) m/z 440 (M+H)+
실시예 172: N-(4-(1-(((1- 시아노시클로프로필 ) 메틸 )술포닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(((1-cyanocyclopropyl)methyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00272
MS(ESI+) m/z 426 (M+H)+
실시예 173: N-(4-(1-((3,4- 디플루오로페닐 )술포닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-((3,4-difluorophenyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00273
MS(ESI+) m/z 459 (M+H)+
실시예 174: N-(4-(8-( 에틸술포닐 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(ethylsulfonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00274
MS(ESI+) m/z 401 (M+H)+
실시예 175: N-(4-(8-((3- 플루오로프로필 )술포닐)-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]사이클로프로판 카르복사미드 (N-(4-(8-((3-fluoropropyl)sulfonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00275
MS(ESI+) m/z 433 (M+H)+
실시예 176: N-(4-(8-( 프로필술포닐 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(propylsulfonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00276
MS(ESI+) m/z 415 (M+H)+
실시예 177: N-(4-(8-( 시클로프로필술포닐 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(cyclopropylsulfonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00277
MS(ESI+) m/z 413 (M+H)+
실시예 178: N-(4-(8-((3,4- 디플루오로페닐 )술포닐)-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-((3,4-difluorophenyl)sulfonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00278
MS(ESI+) m/z 485 (M+H)+
실시예 179: N-(4-(1-( 에틸술포닐 )-3,3-디메틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(ethylsulfonyl)-3,3-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00279
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.53 (s, 1H), 7.74 (s, 1H), 7.28 (dd, J = 2.4, 3.5 Hz, 1H), 6.28 (dd, J = 1.9, 3.5 Hz, 1H), 5.62 (t, J = 3.2 Hz, 1H), 3.89 (d, J = 3.2 Hz, 2H), 3.19 (s, 2H), 3.15 (t, J = 7.3 Hz, 2H), 2.01 (s, 1H), 1.27 (t, J = 7.4 Hz, 3H), 1.04 (s, 6H), 0.82 - 0.75 (m, 4H)
MS(ESI+) m/z 403 (M+H)+
실시예 180: N-(4-(1-((3- 시아노프로필 )술포닐)-3,3-디메틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-((3-cyanopropyl)sulfonyl)-3,3-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00280
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.54 (s, 1H), 7.74 (s, 1H), 7.29 (dd, J = 2.4, 3.5 Hz, 1H), 6.28 (dd, J = 1.9, 3.5 Hz, 1H), 5.62 (t, J = 3.2 Hz, 1H), 3.90 (d, J = 3.2 Hz, 2H), 3.28 - 3.18 (m, 4H), 2.68 (t, J = 7.2 Hz, 2H), 2.03 (q, J = 7.5 Hz, 3H), 1.05 (s, 6H), 0.82 - 0.76 (m, 4H)
MS(ESI+) m/z 442 (M+H)+
실시예 181: N-(4-(4-((3,4- 디플루오로페닐 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3,4-difluorophenyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00281
MS(ESI+) m/z 470 (M+H)+
실시예 182: N-(4-(4-( 에틸술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00282
MS(ESI+) m/z 386 (M+H)+
실시예 183: N-(4-(4-( 시클로헥산술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-( cyclohexanesulfonamido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00283
MS(ESI+) m/z 440 (M+H)+
실시예 184: N-(4-(4-((4,4,4- 트리플루오로부틸 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((4,4,4-trifluorobutyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00284
MS(ESI+) m/z 468 (M+H)+
실시예 185: N-(4-(4-((3-플루오로프로필)술폰아미도)페닐)-7H-피롤로[2,3-d]피리미딘-2-일)시클로 프로판 카르복사미드(N-(4-(4-((3-fluoropropyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00285
MS(ESI+) m/z 418 (M+H)+
실시예 186: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00286
MS(ESI+) m/z 425 (M+H)+
실시예 187: N-(4-(4-((4- 클로로페닐 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((4-chlorophenyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00287
MS(ESI+) m/z 468, 470 (M+H)+
실시예 188: N-(4-(4-((4- 플루오로페닐 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((4-fluorophenyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00288
MS(ESI+) m/z 452 (M+H)+
실시예 189: N-(4-(4-((4- 브로모페닐 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((4-bromophenyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00289
MS(ESI+) m/z 512, 514 (M+H)+
실시예 190: N-(4-(4-( 프로필술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-( propylsulfonamido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00290
MS(ESI+) m/z 400 (M+H)+
실시예 191: N-(4-(4-( 부틸술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-( butylsulfonamido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00291
MS(ESI+) m/z 414 (M+H)+
실시예 192: N-(4-(4-((3- 플루오로페닐 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3-fluorophenyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00292
MS(ESI+) m/z 452 (M+H)+
실시예 193: N-(4-(4-(3,4- 디플루오로 -N- 메틸페닐술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3,4-difluoro-N-methylphenyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00293
MS(ESI+) m/z 484 (M+H)+
실시예 194: N-(4-(4-((3,3,3- 트리플루오로프로필 ) 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3,3,3-trifluoropropyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00294
MS(ESI+) m/z 454 (M+H)+
실시예 195: N-(4-(4-((1,1- 디옥시도테트라히드로 -2H- 티오피란 )-4- 술폰아미도 )페닐)-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(4-((1,1-dioxidotetrahydro-2H-thiopyran)-4-sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00295
MS(ESI+) m/z 490 (M+H)+
실시예 196: N-(4-(4-((1,1- 디옥시도테트라히드로티오펜 )-3- 술폰아미도 )페닐)-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(4-((1,1-dioxidotetrahydrothiophene)-3-sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00296
MS(ESI+) m/z 476 (M+H)+
실시예 197: N-(4-(4-((6- 시아노피리딘 )-3- 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((6-cyanopyridine)-3-sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00297
MS(ESI+) m/z 460 (M+H)+
실시예 198: N-(4-(4-((1- 메틸 -1H-이미다졸)-5- 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일) 시클로프로판카르복사미드 (N-(4-(4-((1-methyl-1H-imidazole)-5-sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00298
MS(ESI+) m/z 438 (M+H)+
실시예 199: N-(4-(4-((1- 메틸 -1H- 피라졸 )-4- 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((1-methyl-1H-pyrazole)-4-sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00299
MS(ESI+) m/z 438 (M+H)+
실시예 200: 4 -(N-(4-(2-( 시클로프로판카르복사미도 )-7H- 피롤로[2,3-d]피리미딘 -4-일)페닐)술파모일)벤즈아미드 (4-(N-(4-(2-( cyclopropanecarboxamido )-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)sulfamoyl)benzamide)의 합성
Figure pat00300
MS(ESI+) m/z 477 (M+H)+
실시예 201: N-(4-(3- 플루오로 -4-( 메틸술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-(methylsulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00301
1H NMR (400 MHz, DMSO-d6) δ 12.10 (s, 1H), 10.62 (s, 1H), 8.06 (d, J = 9.4 Hz, 2H), 7.62 (t, J = 8.4 Hz, 1H), 7.52 (s, 1H), 6.88 (s, 1H), 3.13 (s, 3H), 2.17 (s, 1H), 0.82 (d, J = 17.7 Hz, 4H)
MS(ESI+) m/z 390 (M+H)+
실시예 202: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido )-3-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00302
1H NMR (400 MHz, DMSO-d6) δ 12.10 (s, 1H), 10.62 (s, 1H), 9.94 (s, 1H), 8.15 - 7.99 (m, 2H), 7.63 (t, J = 8.3 Hz, 1H), 7.57 - 7.47 (m, 1H), 6.94 - 6.84 (m, 1H), 3.21 (q, J = 7.3 Hz, 2H), 2.17 (s, 1H), 1.28 (t, J = 7.1 Hz, 3H), 0.88 - 0.75 (m, 4H)
MS(ESI+) m/z 404 (M+H)+
실시예 203: N-(4-(3- 플루오로 -4-((3- 플루오로프로필 ) 술폰아미도 )페닐)-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-((3-fluoropropyl)sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00303
1H NMR (400 MHz, DMSO-d6) δ 12.10 (s, 1H), 10.62 (s, 1H), 10.08 (s, 1H), 8.06 (d, J = 9.9 Hz, 2H), 7.63 (t, J = 8.2 Hz, 1H), 7.56 - 7.48 (m, 1H), 6.95 - 6.85 (m, 1H), 4.55 (dt, J = 6.0, 47.4 Hz, 2H), 2.14 (dd, J = 8.0, 22.9 Hz, 3H), 0.84 - 0.78 (m, 4H)
MS(ESI+) m/z 436 (M+H)+
실시예 204: N-(4-(4-((3- 시아노프로필 ) 술폰아미도 )-3- 플루오로페닐 )-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3-cyanopropyl)sulfonamido)-3-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00304
1H NMR (400 MHz, DMSO-d6) δ 12.10 (s, 1H), 10.63 (s, 1H), 10.12 (s, 1H), 8.06 (d, J = 10.0 Hz, 2H), 7.62 (t, J = 8.3 Hz, 1H), 7.58 - 7.46 (m, 1H), 6.95 - 6.78 (m, 1H), 2.69 (t, J = 7.1 Hz, 2H), 2.17 (s, 1H), 2.07 (q, J = 7.3 Hz, 2H), 0.88 - 0.80 (m, 4H)
MS(ESI+) m/z 443 (M+H)+
실시예 205: N-(4-(4-((3,4- 디플루오로페닐 ) 술폰아미도 )-3- 플루오로페닐 )-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(4-((3,4-difluorophenyl)sulfonamido)-3-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00305
1H NMR (400 MHz, DMSO-d6) δ 12.11 (s, 1H), 10.67 (s, 1H), 10.62 (s, 1H), 8.06 - 7.93 (m, 2H), 7.91 - 7.83 (m, 1H), 7.76 - 7.61 (m, 2H), 7.57 - 7.44 (m, 2H), 6.91 - 6.78 (m, 1H), 2.14 (s, 1H), 0.90 - 0.74 (m, 4H)
MS(ESI+) m/z 488 (M+H)+
실시예 206: N-(4-(3-플루오로-4-(프로필술폰아미도)페닐)-7H-피롤로[2,3-d]피리미딘-2-일)시클로 프로판 카르복사미드 (N-(4-(3-fluoro-4-(propylsulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00306
MS(ESI+) m/z 418 (M+H)+
실시예 207: N-(7-(4-( 에틸술폰아미도 )페닐)-3H- 이미다조[4,5-b]피리딘 -5-일)시클로프로판카르복사미드 (N-(7-(4-( ethylsulfonamido ) phenyl )-3H-imidazo[4,5-b]pyridin-5-yl)cyclopropanecarboxamide)의 합성
Figure pat00307
MS(ESI+) m/z 386 (M+H)+
실시예 208: N-(6-(4-((3,4- 디플루오로페닐 ) 술폰아미도 )페닐)-9H- 푸린 -2-일)시클로프로판카르복사미드 (N-(6-(4-((3,4- difluorophenyl ) sulfonamido ) phenyl )-9H-purin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00308
1H NMR (400 MHz, DMSO-d6) δ 10.80 (s, 1H), 10.72 (s, 1H), 8.81 - 8.61 (m, 2H), 8.45 (s, 1H), 7.92 (ddd, J = 9.7, 7.3, 2.2 Hz, 1H), 7.76 - 7.59 (m, 2H), 7.36 - 7.28 (m, 2H), 2.16 (s, 1H), 0.85 - 0.77 (m, 4H)
MS(ESI+) m/z 471 (M+H)+
실시예 209: N-(6-(4-( 에틸술폰아미도 )페닐)-9H- 푸린 -2-일) 시클로프로판카르복사미드 (N-(6-(4-( ethylsulfonamido ) phenyl )-9H- purin -2-yl)cyclopropanecarboxamide)의 합성
Figure pat00309
1H NMR (400 MHz, DMSO-d6) δ 10.73 (s, 1H), 10.18 (s, 1H), 8.77 (d, J = 8.4 Hz, 2H), 8.46 (d, J = 1.3 Hz, 1H), 7.46 - 7.34 (m, 2H), 3.26 - 3.18 (m, 2H), 2.26 - 2.13 (m, 1H), 1.22 (td, J = 7.4, 1.3 Hz, 3H), 0.92 - 0.80 (m, 4H)
MS(ESI+) m/z 387 (M+H)+
실시예 210: N-(6-(4-((3- 시아노프로필 ) 술폰아미도 )페닐)-9H- 푸린 -2-일) 시클로프로판카르복사미드 (N-(6-(4-((3- cyanopropyl ) sulfonamido ) phenyl )-9H- purin -2-yl)cyclopropanecarboxamide)의 합성
Figure pat00310
1H NMR (400 MHz, DMSO-d6) δ 10.77 (s, 1H), 10.32 (s, 1H), 8.83 - 8.75 (m, 2H), 8.48 (s, 1H), 7.45 - 7.36 (m, 2H), 3.59 (dq, J = 12.1, 6.0 Hz, 2H), 3.35 - 3.25 (m, 2H), 2.19 (dt, J = 7.8, 3.3 Hz, 1H), 2.00 (dq, J = 9.5, 7.4 Hz, 2H), 1.03 (d, J = 6.1 Hz, 6H), 0.91 - 0.79 (m, 4H)
MS(ESI+) m/z 426 (M+H)+
실시예 211: N-(6-(4-((4,4,4- 트리플루오로부틸 ) 술폰아미도 )페닐)-9H- 푸린 -2-일)시클로프로판카르복사미드 (N-(6-(4-((4,4,4-trifluorobutyl)sulfonamido)phenyl)-9H-purin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00311
1H NMR (400 MHz, DMSO-d6) δ 10.74 (s, 1H), 10.31 (s, 1H), 8.78 (d, J = 8.7 Hz, 2H), 8.47 (s, 1H), 7.43 - 7.35 (m, 2H), 3.34 (t, J = 7.6 Hz, 2H), 2.49 - 2.34 (m, 2H), 2.19 (td, J = 7.3, 3.7 Hz, 1H), 1.97 - 1.84 (m, 2H), 0.86 - 0.78 (m, 4H)
MS(ESI+) m/z 469 (M+H)+
실시예 212: N-(4-(1-( 프로필술포닐 )-2,5- 디히드로 -1H-피롤-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(propylsulfonyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00312
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 10.61 (s, 1H), 7.82 (s, 1H), 7.43 (t, J = 2.9 Hz, 1H), 6.70 (td, J = 1.9, 3.6, 4.2 Hz, 2H), 4.58 (t, J = 4.4 Hz, 2H), 4.40 (q, J = 3.8 Hz, 2H), 3.26 - 3.15 (m, 2H), 2.03 (tt, J = 4.5, 7.7 Hz, 1H), 1.80 - 1.65 (m, 2H), 1.00 (t, J = 7.4 Hz, 3H), 0.83-0.76 (m, 4H)
MS(ESI+) m/z 375 (M+H)+
실시예 213: N-(4-(1-(((1- 시아노시클로프로필 ) 메틸 )술포닐)-2,5- 디히드로 -1H-피롤-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(((1-cyanocyclopropyl)methyl)sulfonyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00313
1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 10.62 (s, 1H), 7.83 (s, 1H), 7.52 - 7.35 (m, 1H), 6.75 - 6.65 (m, 2H), 4.64 (dd, J = 3.1, 6.2 Hz, 2H), 4.46 (q, J = 3.2, 3.7 Hz, 2H), 3.61 (s, 2H), 2.02 (td, J = 4.0, 7.6 Hz, 1H), 1.40 (q, J = 4.3, 4.7 Hz, 2H), 1.22 (q, J = 4.9 Hz, 2H), 0.89 - 0.73 (m, 4H)
MS(ESI+) m/z 412 (M+H)+
실시예 214: N-(4-(4-(모르폴린-4- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( morpholine -4- sulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00314
출발물질 N-(4-(4-아미노페닐)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-aminophenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-6-yl) cyclopropanecarboxamide) (100 mg)를 피리딘 1 mL 에서 교반하였다. 모르폴린-4-설포닐클로라이드 1.5당량을 넣고, 40 oC에서 16시간 동안 교반하였다. 반응이 완료되면 상기 혼합물을 d-HCl을 첨가하고, 디클로로메탄으로 추출하여, 유기층을 분리하였다. 혼합물 농축 후, MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 oC에서 12시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온으로 냉각시키고, 교반하면서 포화된 NH4Cl 수용액을 첨가하였다. 생성된 고체를 여과하여 생성물인 N-(4-(4-(모르폴린-4-술폰아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.69 (s, 1H), 10.24 (s, 1H), 7.97 (d, J = 5.7 Hz, 1H), 7.69 (d, J = 7.6 Hz, 2H), 7.47 (d, J = 8.2 Hz, 1H), 7.43 - 7.33 (m, 3H), 7.11 (d, J = 7.8 Hz, 1H), 6.62 - 6.51 (m, 1H), 3.63 - 3.50 (m, 5H), 3.18 - 3.06 (m, 5H), 2.05 (d, J = 8.9 Hz, 1H), 0.88 - 0.77 (m, 4H)
MS(ESI+) m/z 442 (M+H)+
실시예 215 내지 238
이하 실시예 215 내지 실시예 238에서는, 실시예 214와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 215: N-(4-(4-((N-에틸-N- 메틸술파모일 )아미노)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((N-ethyl-N-methylsulfamoyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00315
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.59 (s, 1H), 10.07 (s, 1H), 7.99 (s, 1H), 7.71 - 7.60 (m, 2H), 7.43 - 7.35 (m, 1H), 7.31 (d, J = 8.5 Hz, 2H), 6.58 - 6.48 (m, 1H), 3.18 (q, J = 7.2 Hz, 2H), 2.74 (s, 3H), 2.04 (s, 1H), 1.04 (t, J = 7.0 Hz, 3H), 0.88 - 0.74 (m, 4H)
MS(ESI+) m/z 414 (M+H)+
실시예 216: N-(4-(4-(( N,N - 디에틸술파모일 )아미노)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((N,N-diethylsulfamoyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00316
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.59 (s, 1H), 10.02 (s, 1H), 7.99 (s, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.44 - 7.19 (m, 3H), 6.54 (d, J = 10.6 Hz, 1H), 3.23 (t, J = 6.9 Hz, 4H), 2.04 (s, 1H), 1.01 (t, J = 7.2 Hz, 6H), 0.88 - 0.76 (m, 4H)
MS(ESI+) m/z 428 (M+H)+
실시예 217: N-(4-(4-((N- 시클로프로필 -N- 메틸술파모일 )아미노)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((N-cyclopropyl-N-methylsulfamoyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00317
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.59 (s, 1H), 10.26 (s, 1H), 7.98 (s, 1H), 7.65 (d, J = 8.1 Hz, 2H), 7.45 - 7.26 (m, 3H), 6.54 (s, 1H), 2.80 (t, J = 5.5 Hz, 3H), 2.34 (s, 1H), 2.04 (s, 1H), 0.88 - 0.76 (m, 4H), 0.63 (d, J = 22.6 Hz, 4H)
MS(ESI+) m/z 426 (M+H)+
실시예 218: N-(4-(4-( 피롤리딘 -1- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( pyrrolidine -1- sulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00318
MS(ESI+) m/z 426 (M+H)+
실시예 219: N-(4-(4-(피페리딘-1- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( piperidine -1- sulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00319
MS(ESI+) m/z 440 (M+H)+
실시예 220: N-(4-(4-((2,6-디메틸모르폴린)-4- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((2,6-dimethylmorpholine)-4-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00320
MS(ESI+) m/z 470 (M+H)+
실시예 221: N-(4-(4-((3- 시아노아제티딘 )-1- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3- cyanoazetidine )-1-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00321
MS(ESI+) m/z 437 (M+H)+
실시예 222: N-(4-(4-((N-이소프로필-N- 메틸술파모일 )아미노)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((N-isopropyl-N-methylsulfamoyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00322
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.58 (s, 1H), 10.06 (s, 1H), 7.98 (s, 1H), 7.65 (d, J = 7.9 Hz, 2H), 7.38 (s, 1H), 7.26 (d, J = 9.5 Hz, 2H), 6.52 (s, 1H), 4.03 (s, 1H), 2.65 (t, J = 5.8 Hz, 3H), 2.04 (s, 1H), 1.03 - 0.95 (m, 6H), 0.81 (s, 4H)
MS(ESI+) m/z 428 (M+H)+
실시예 223: N-(4-(4-((N-(2- 메톡시에틸 )-N- 메틸술파모일 )아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((N-(2-methoxyethyl)-N-methylsulfamoyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00323
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.59 (s, 1H), 10.07 (s, 1H), 7.99 (s, 1H), 7.66 (d, J = 9.1 Hz, 2H), 7.35 (t, J = 14.4 Hz, 3H), 6.53 (s, 1H), 3.41 (s, 2H), 3.19 (q, J = 5.6, 6.3 Hz, 3H), 2.81 (t, J = 5.9 Hz, 3H), 2.04 (s, 1H), 0.90 - 0.73 (m, 4H)
MS(ESI+) m/z 444 (M+H)+
실시예 224: N-(4-(3- 플루오로 -4-(피페리딘-1- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-(piperidine-1-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00324
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.68 (s, 1H), 9.85 (s, 1H), 8.02 (s, 1H), 7.61 (t, J = 8.2 Hz, 1H), 7.54 (d, J = 9.9 Hz, 2H), 7.43 (t, J = 3.0 Hz, 1H), 6.58 - 6.54 (m, 1H), 3.12 (d, J = 6.2 Hz, 4H), 2.04 (s, 1H), 1.47 (d, J = 20.7 Hz, 6H), 0.85 - 0.78 (m, 4H)
MS(ESI+) m/z 458 (M+H)+
실시예 225: N-(4-(3- 플루오로 -4-( 피롤리딘 -1- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-(pyrrolidine-1-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00325
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.67 (s, 1H), 9.81 (s, 1H), 8.01 (s, 1H), 7.62 (t, J = 8.3 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.43 (t, J = 3.0 Hz, 1H), 6.55 (dd, J = 3.6, 1.9 Hz, 1H), 3.21 (d, J = 6.0 Hz, 4H), 2.04 (s, 1H), 1.83 - 1.72 (m, 4H), 0.90 - 0.70 (m, 4H)
MS(ESI+) m/z 444 (M+H)+
실시예 226: N-(4-(3- 플루오로 -4-(모르폴린-4- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3- fluoro -4-( morpholine -4-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00326
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.69 (s, 1H), 10.02 (s, 1H), 8.03 (s, 1H), 7.63 (t, J = 8.4 Hz, 1H), 7.60 - 7.52 (m, 2H), 7.44 (t, J = 3.0 Hz, 1H), 6.56 (dd, J = 3.6, 1.9 Hz, 1H), 3.60 (t, J = 4.7 Hz, 4H), 3.10 (t, J = 4.7 Hz, 4H), 2.04 (s, 1H), 0.90 - 0.68 (m, 4H)
MS(ESI+) m/z 460 (M+H)+
실시예 227: N-(4-(2- 메틸 -4-((N-(2,2,2- 트리플루오로에틸 ) 술파모일 )아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(2-methyl-4-((N-(2,2,2-trifluoroethyl)sulfamoyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00327
1H NMR (400 MHz, DMSO-d6) δ 11.59 - 11.42 (m, 1H), 10.63 (s, 1H), 7.76 (s, 1H), 7.38 - 7.26 (m, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.15 (d, J = 2.2 Hz, 1H), 7.09 (dd, J = 2.4, 8.3 Hz, 1H), 6.07 (dd, J = 1.9, 3.5 Hz, 1H), 3.70 (q, J = 9.6 Hz, 2H), 2.14 (s, 3H), 2.04 (d, J = 7.2 Hz, 1H), 0.82 - 0.75 (m, 4H)
MS(ESI+) m/z 468 (M+H)+
실시예 228: N-(4-(2- 메틸 -4-((N- 메틸 -N-(2,2,2- 트리플루오로에틸 ) 술파모일 )아미노)페닐)-1H-피롤로[2,3-b]사이클로프로판 카르복사미드 (N-(4-(2-methyl-4-((N-methyl-N-(2,2,2-trifluoroethyl)sulfamoyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00328
1H NMR (400 MHz, DMSO-d6) δ 11.50 (d, J = 6.3 Hz, 1H), 10.64 (s, 1H), 7.77 (s, 1H), 7.34 (d, J = 3.7 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.17 - 7.07 (m, 2H), 6.09 - 6.04 (m, 1H), 4.06 (d, J = 10.1 Hz, 2H), 2.92 - 2.85 (m, 3H), 2.14 (s, 3H), 2.04 (s, 1H), 0.82 - 0.75 (m, 4H)
MS(ESI+) m/z 482 (M+H)+
실시예 229: N-(4-(4-((1,1- 디옥시도티오모르폴린 )-4- 술폰아미도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1,1-dioxidothiomorpholine)-4-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00329
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 1H), 10.39 (s, 1H), 8.01 (s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.38 (t, J = 6.7 Hz, 3H), 6.58 - 6.50 (m, 1H), 3.66 (d, J = 5.5 Hz, 4H), 3.16 (d, J = 5.3 Hz, 4H), 2.04 (s, 1H), 0.85 - 0.76 (m, 4H)
MS(ESI+) m/z 490 (M+H)+
실시예 230: N-(4-(4-((4-( 메틸술포닐 )피페라진)-1- 술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-(methylsulfonyl)piperazine)-1-sulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00330
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.61 (s, 1H), 10.30 (s, 1H), 8.00 (s, 1H), 7.69 (d, J = 8.3 Hz, 2H), 7.42 - 7.34 (m, 3H), 6.54 (d, J = 2.9 Hz, 1H), 3.26 (t, J = 4.8 Hz, 4H), 3.13 (d, J = 5.5 Hz, 4H), 2.85 (s, 3H), 2.04 (s, 1H), 0.85 - 0.77 (m, 4H)
MS(ESI+) m/z 519 (M+H)+
실시예 231: N-(4-(4-(모르폴린-4- 술폰아미도 ) 시클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(morpholine-4-sulfonamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00331
1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.83 (d, J = 3.1 Hz, 1H), 7.31 (s, 1H), 6.51 (s, 1H), 6.19 (d, J = 4.1 Hz, 1H), 3.66 (d, J = 4.7 Hz, 4H), 3.06 - 2.99 (m, 4H), 2.58 (d, J = 22.0 Hz, 4H), 2.25 (d, J = 14.2 Hz, 1H), 2.01 (d, J = 12.6 Hz, 2H), 1.70 (s, 1H), 0.84 - 0.76 (m, 4H)
MS(ESI+) m/z 446 (M+H)+
실시예 232: N-(4-(1-(N-(2,2,2- 트리플루오로에틸 ) 설파모일 )-1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(N-(2,2,2-trifluoroethyl)sulfamoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00332
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.55 (s, 1H), 8.10 (s, 1H), 7.87 (s, 1H), 7.41 - 7.29 (m, 1H), 6.57 (s, 1H), 6.36 (s, 1H), 3.89 (s, 2H), 3.79 (d, J = 10.4 Hz, 2H), 2.64 (s, 2H), 2.07 - 1.97 (m, 1H), 0.79 (d, J = 12.6 Hz, 4H)
MS(ESI+) m/z 444 (M+H)+
실시예 233: N-(4-(1-(N-메틸-N-(2,2,2-트리플루오로에틸)술파모일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(N-methyl-N-(2,2,2-trifluoroethyl)sulfamoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00333
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.55 (s, 1H), 7.87 (d, J = 3.8 Hz, 1H), 7.36 (s, 1H), 6.56 (s, 1H), 6.35 (s, 1H), 4.11 (d, J = 10.7 Hz, 2H), 3.96 (s, 2H), 3.48 (s, 4H), 2.93 (d, J = 3.8 Hz, 2H), 2.63 (s, 2H), 2.02 (s, 1H), 0.79 (d, J = 12.0 Hz, 4H)
MS(ESI+) m/z 458 (M+H)+
실시예 234: N-(4-(1-( 모르폴리노술포닐 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(morpholinosulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00334
MS(ESI+) m/z 432 (M+H)+
실시예 235: N-(4-(4-(모르폴린-4- 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-( morpholine -4- sulfonamido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00335
MS(ESI+) m/z 443 (M+H)+
실시예 236: N-(4-(4-(( N,N - 디메틸술파모일 )아미노)페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((N,N-dimethylsulfamoyl)amino)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00336
MS(ESI+) m/z 401 (M+H)+
실시예 237: N-(4-(4-((2,6-디메틸모르폴린)-4- 술폰아미도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((2,6-dimethylmorpholine)-4-sulfonamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00337
1H NMR (400 MHz, DMSO-d6) δ 12.01 (s, 1H), 10.56 (s, 1H), 10.30 (s, 1H), 8.19 - 8.13 (m, 2H), 7.51 - 7.45 (m, 2H), 7.38 (dd, J = 2.1, 9.1 Hz, 2H), 6.84 (dd, J = 1.8, 3.7 Hz, 1H), 3.53 - 3.45 (m, 4H), 2.41 (d, J = 14.6 Hz, 2H), 2.19 (d, J = 9.7 Hz, 1H), 1.06 (dd, J = 2.9, 6.4 Hz, 6H), 0.89 - 0.75 (m, 4H)
MS(ESI+) m/z 471 (M+H)+
실시예 238: N-(6-(4-(모르폴린-4- 술폰아미도 )페닐)-9H- 푸린 -2-일) 시클로프로판카르복사미드 (N-(6-(4-( morpholine -4- sulfonamido ) phenyl )-9H- purin -2-yl)cyclopropanecarboxamide)의 합성
Figure pat00338
1H NMR (400 MHz, DMSO-d6) δ 10.74 (s, 1H), 10.39 (s, 1H), 8.77 (d, J = 8.5 Hz, 2H), 8.47 (s, 1H), 7.39 (d, J = 8.4 Hz, 2H), 3.55 (t, J = 4.8 Hz, 4H), 3.13 (t, J = 4.7 Hz, 4H), 2.18 (dd, J = 8.7, 4.3 Hz, 1H), 0.90 - 0.77 (m, 4H)
MS(ESI+) m/z 444 (M+H)+
실시예 239: N-(4-(4-(2-시아노아세트아미도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드(N-(4-(4-(2-cyanoacetamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00339
2-시아노아세트산 1.2 당량을 디클로로메탄 용액에 넣고, EDCI 1.6당량을 첨가하였다. 혼합물에 HOBt 1.4당량, DMAP 1.1당량, 그리고 합성된 N-(4-(4-아미노페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (100 mg)를 넣고, 실온에서 교반하였다. 반응이 완료된 후 상기 혼합물에 H2O을 첨가하였고, 디클로로메탄으로 추출하여, 유기층을 분리하였다. 혼합물을 농축 후, 컬럼크로마토그래피로 분리하고, 생성물인 N-(4-(4-(2-시아노아세트아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 1H), 10.50 (s, 1H), 8.19 (d, J = 6.7 Hz, 2H), 8.02 (s, 1H), 7.40 (s, 1H), 6.89 (d, J = 6.8 Hz, 2H), 6.56 (s, 1H), 3.13 (s, 2H), 0.81 (d, J = 6.6 Hz, 4H)
MS(ESI+) m/z 360 (M+H)+
실시예 240 내지 430
이하, 실시예 240 내지 실시예 430에서는, 실시예 239와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 240: N-(4-(4-(2- 시아노아세트아미도 )-2- 메틸페닐 )-1H- 피롤[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- cyanoacetamido )-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00340
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.62 (s, 1H), 10.41 (s, 1H), 7.78 (s, 1H), 7.54 (s, 1H), 7.49 (d, J = 8.5 Hz, 1H), 7.33 (t, J = 2.9 Hz, 1H), 7.25 (d, J = 8.2 Hz, 1H), 6.07 (dd, J = 3.4, 1.8 Hz, 1H), 3.93 (s, 2H), 2.15 (s, 3H), 2.03 (s, 1H), 0.84 - 0.75 (m, 4H)
MS(ESI+) m/z 374 (M+H)+
실시예 241: N-(4-(4-(2-(1- 시아노시클로프로필 ) 아세트아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1-cyanocyclopropyl)acetamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00341
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 10.19 (s, 1H), 8.10 (d, J = 6.2 Hz, 1H), 7.78 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.40 (t, J = 3.0 Hz, 1H), 6.56 (t, J = 2.5 Hz, 1H), 2.05 (s, 1H), 1.28 (t, J = 3.8 Hz, 2H), 1.06 (q, J = 5.1 Hz, 2H), 0.88 - 0.79 (m, 4H)
MS(ESI+) m/z 400 (M+H)+
실시예 242: N-(4-(4- 프로피온아미도시클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4- propionamidocyclohex -1- en -1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00342
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.52 (s, 1H), 7.89 - 7.74 (m, 2H), 7.31 (dd, J = 2.5, 3.5 Hz, 1H), 6.51 (dd, J = 1.8, 3.5 Hz, 1H), 6.26 - 6.18 (m, 1H), 3.90 (s, 1H), 2.14 (d, J = 13.0 Hz, 1H), 2.08 (t, J = 7.6 Hz, 2H), 2.05 - 1.88 (m, 2H), 1.69 - 1.58 (m, 1H), 1.01 (t, J = 7.6 Hz, 3H), 0.84 - 0.76 (m, 4H)
MS(ESI+) m/z 353 (M+H)+
실시예 243: N-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)시클로헥스-3-엔-1-일)벤즈아미드 (N-(4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohex-3-en-1-yl)benzamide)의 합성
Figure pat00343
1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.53 (s, 1H), 8.40 (d, J = 7.7 Hz, 1H), 7.88 (dt, J = 1.6, 7.1 Hz, 3H), 7.56 - 7.43 (m, 3H), 7.32 (dd, J = 2.4, 3.5 Hz, 1H), 6.54 (dd, J = 1.8, 3.6 Hz, 1H), 6.32 - 6.22 (m, 1H), 4.15 (d, J = 3.5 Hz, 1H), 2.71 - 2.54 (m, 4H), 2.41 - 2.29 (m, 1H), 2.04 (d, J = 13.0 Hz, 2H), 1.81 (tq, J = 5.6, 11.8 Hz, 1H), 0.85 - 0.74 (m, 4H)
MS(ESI+) m/z 401 (M+H)+
실시예 244: N-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)시클로헥스-3-엔-1-일)-2-메틸시클로프로판-1-카르복사미드 (N-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohex-3-en-1-yl)-2-methylcyclopropane-1-carboxamide)의 합성
Figure pat00344
MS(ESI+) m/z 379 (M+H)+
실시예 245: N-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)시클로헥스-3-엔-1-일)시클로펜탄 카르복사미드 (N-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohex-3-en-1-yl)cyclopentanecarboxamide)의 합성
Figure pat00345
MS(ESI+) m/z 393 (M+H)+
실시예 246: N-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)시클로헥스-3-엔-1-일)시클로프로판카르복사미드 (N-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohex-3-en-1-yl)cyclopropanecarboxamide)의 합성
Figure pat00346
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.51 (s, 1H), 8.13 (d, J = 7.5 Hz, 1H), 7.84 (s, 1H), 7.31 (d, J = 3.5 Hz, 1H), 6.52 (d, J = 3.5 Hz, 1H), 6.24 (d, J = 4.5 Hz, 1H), 3.92 (s, 1H), 2.60 - 2.54 (m, 2H), 2.20 - 2.09 (m, 1H), 2.00 (d, J = 5.0 Hz, 1H), 1.94 (d, J = 12.3 Hz, 1H), 1.70 - 1.54 (m, 2H), 0.82 - 0.74 (m, 4H), 0.71 - 0.59 (m, 4H)
MS(ESI+) m/z 365 (M+H)+
실시예 247: N-(4-(4-(2- 시아노아세트아미도 ) 시클로헥스 -1-엔-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-cyanoacetamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00347
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.54 (s, 1H), 8.31 (d, J = 7.3 Hz, 1H), 7.82 (s, 1H), 7.36 - 7.26 (m, 1H), 6.53 (dd, J = 1.9, 3.6 Hz, 1H), 6.24 (s, 1H), 3.94 (s, 1H), 3.64 (s, 2H), 2.56 (d, J = 6.3 Hz, 3H), 2.21 - 2.09 (m, 1H), 2.05 - 1.98 (m, 1H), 1.98 - 1.90 (m, 1H), 1.76 - 1.65 (m, 1H), 0.87 - 0.72 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 248: N-(4-(4-(4,4,4- 트리플루오로부탄아미도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(4,4,4-trifluorobutanamido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00348
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 8.06 (d, J = 7.5 Hz, 1H), 7.85 (d, J = 7.5 Hz, 1H), 7.31 (q, J = 3.0, 3.6 Hz, 1H), 6.52 (dd, J = 1.9, 3.6 Hz, 1H), 6.23 (d, J = 4.4 Hz, 1H), 3.94 (d, J = 10.0 Hz, 1H), 2.92 (d, J = 22.6 Hz, 1H), 2.74 - 2.65 (m, 2H), 2.55 (s, 3H), 2.38 (dd, J = 6.4, 8.7 Hz, 2H), 2.18 - 2.07 (m, 1H), 2.05 - 1.98 (m, 1H), 1.93 (dd, J = 4.9, 12.4 Hz, 1H), 1.67 (q, J = 9.7, 12.2 Hz, 1H), 1.25 - 1.19 (m, 4H), 0.86 - 0.74 (m, 4H)
MS(ESI+) m/z 421 (M+H)+
실시예 249: N-(4-(1-(1,1-디옥시도테트라히드로-2H-티오피란-4-카르보닐)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1,1-dioxidotetrahydro-2H-thiopyran-4-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00349
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.54 (s, 1H), 7.87 (s, 1H), 7.35 (s, 1H), 6.57 (s, 1H), 6.34 (d, J = 29.7 Hz, 1H), 4.38 - 3.97 (m, 3H), 3.75 (d, J = 15.9 Hz, 2H), 3.11 (d, J = 14.9 Hz, 5H), 2.64 (s, 2H), 2.02 (d, J = 20.0 Hz, 6H), 1.26 - 1.12 (m, 2H), 0.85 - 0.76 (m, 4H)
MS(ESI+) m/z 443 (M+H)+
실시예 250 N-(4-(1-(2- 시아노아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00350
1H NMR (400 MHz, Chloroform-d) δ 11.44 (s, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.41 - 7.31 (m, 1H), 6.55 (s, 1H), 6.31 (d, J = 25.9 Hz, 1H), 4.26 - 4.04 (m, 4H), 3.77 - 3.67 (m, 1H), 3.59 (t, J = 5.3 Hz, 1H), 3.17 (s, 1H), 2.65 (s, 1H), 2.02 (s, 1H), 0.84 - 0.78 (m, 4H)
MS(ESI+) m/z 350 (M+H)+
실시예 251: N-(4-(1-(2-(1,1- 디옥시도티오모르폴리노 )아세틸)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-(1,1-dioxidothiomorpholino)acetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamid)의 합성
Figure pat00351
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.54 (s, 1H), 7.87 (s, 1H), 7.35 (t, J = 3.1 Hz, 1H), 6.56 (s, 1H), 6.33 (d, J = 24.9 Hz, 1H), 4.51 - 4.36 (m, 2H), 4.35 - 4.20 (m, 2H), 4.06 - 3.93 (m, 1H), 3.86 - 3.67 (m, 2H), 3.64 - 3.48 (m, 2H), 3.21 (d, J = 14.0 Hz, 2H), 3.08 (d, J = 12.0 Hz, 3H), 2.02 (s, 1H), 0.80 (d, J = 8.0 Hz, 4H)
MS(ESI+) m/z 458 (M+H)+
실시예 252: N-(4-(1-(3- 시아노프로파노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-cyanopropanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00352
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.87 (s, 1H), 7.34 (t, J = 3.0 Hz, 1H), 6.59 - 6.52 (m, 1H), 6.33 (d, J = 21.2 Hz, 1H), 4.21 (s, 2H), 3.70 (dt, J = 30.9, 5.5 Hz, 2H), 2.82 (dt, J = 24.0, 6.8 Hz, 2H), 2.70 - 2.59 (m, 4H), 2.01 (d, J = 6.2 Hz, 1H), 0.86 - 0.74 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 253: N-(4-(1-(3,3,3- 트리플루오로프로파노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3,3,3-trifluoropropanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00353
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (d, J = 3.5 Hz, 1H), 7.86 (s, 1H), 7.34 (s, 1H), 6.55 (s, 1H), 6.31 (d, J = 27.5 Hz, 1H), 4.19 (s, 2H), 3.64 (p, J = 6.8, 6.0 Hz, 7H), 2.62 (s, 2H), 2.01 (s, 1H), 0.85 - 0.76 (m, 4H)
MS(ESI+) m/z 393 (M+H)+
실시예 254: N-(4-(1-(4,4,4- 트리플루오로부타노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(4,4,4-trifluorobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00354
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.52 (s, 1H), 7.85 (s, 1H), 7.34 (s, 1H), 6.55 (s, 1H), 6.34 (s, 1H), 4.19 (d, J = 6.5 Hz, 2H), 3.75 (s, 2H), 3.24 (d, J = 10.1 Hz, 4H), 2.65 (d, J = 27.0 Hz, 2H), 2.00 (s, 1H), 0.78 (d, J = 11.5 Hz, 4H)
MS(ESI+) m/z 407 (M+H)+
실시예 255: N-(4-(8-(3- 시아노프로파노일 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(3-cyanopropanoyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00355
MS(ESI+) m/z 390 (M+H)+
실시예 256: N-(4-(8-( 시클로프로판카르보닐 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(cyclopropanecarbonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00356
MS(ESI+) m/z 377 (M+H)+
실시예 257: N-(4-(8-(2- 시아노아세틸 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]-6-일)시클로프로판카르복사미드 (N-(4-(8-(2-cyanoacetyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00357
MS(ESI+) m/z 376 (M+H)+
실시예 258: N-(4-(8-(4,4,4- 트리플루오로부타노일 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00358
MS(ESI+) m/z 433 (M+H)+
실시예 259: N-(4-(1-(1- 시아노시클로프로판 -1-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-cyanocyclopropane-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00359
MS(ESI+) m/z 376 (M+H)+
실시예 260: N-(4-(1-(3,3- 디플루오로사이클로부탄 -1-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3,3-difluorocyclobutane-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00360
1H NMR (400 MHz, DMSO-d6) δ 11.53 - 11.35 (m, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.34 (d, J = 2.8 Hz, 1H), 6.63 - 6.48 (m, 1H), 6.38 - 6.24 (m, 1H), 4.19 (d, J = 8.8 Hz, 2H), 3.68 (dt, J = 5.6, 47.7 Hz, 2H), 2.81 (ddt, J = 5.7, 11.0, 21.2 Hz, 4H), 2.59 (s, 2H), 2.00 (d, J = 14.4 Hz, 1H), 0.85 - 0.73 (m, 4H)
MS(ESI+) m/z 401 (M+H)+
실시예 261: N-(4-(8-(3,3,3- 트리플루오로프로파노일 )-8- 아자바이사이클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(3,3,3-trifluoropropanoyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00361
MS(ESI+) m/z 419 (M+H)+
실시예 262: N-(4-(8-(2- 시아노아세틸 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]-6-일)시클로프로판카르복사미드 (N-(4-(8-(2-cyanoacetyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00362
MS(ESI+) m/z 376 (M+H)+
실시예 263: N-(4-(1-(2,2- 디플루오로시클로프로판 -1-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,2-difluorocyclopropane-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00363
1H NMR (400 MHz, DMSO-d6) δ 10.68 (s, 1H), 8.06 (d, J = 2.3 Hz, 1H), 7.91 (d, J = 4.2 Hz, 1H), 6.94 (dd, J = 5.8, 4.1 Hz, 1H), 6.32 (s, 1H), 5.17 (q, J = 10.6 Hz, 1H), 4.56 - 4.28 (m, 1H), 4.28 - 4.12 (m, 1H), 3.93 (s, 1H), 3.77 (t, J = 5.8 Hz, 2H), 2.75 (s, 1H), 2.38 - 2.29 (m, 1H), 2.23 (d, J = 11.8 Hz, 1H), 2.06 - 1.80 (m, 4H), 0.86 (d, J = 5.7 Hz, 4H)
MS(ESI+) m/z 387 (M+H)+
실시예 264: N-(4-(1-( 시클로프로판카르보닐 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(cyclopropanecarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00364
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.87 (s, 1H), 7.34 (dd, J = 2.5, 3.5 Hz, 1H), 6.56 (dd, J = 1.9, 3.6 Hz, 1H), 6.35 (s, 1H), 4.32 (d, J = 110.2 Hz, 2H), 3.82 (d, J = 78.9 Hz, 2H), 2.65 (d, J = 9.9 Hz, 1H), 2.13 - 1.92 (m, 2H), 0.84 - 0.70 (m, 8H)
MS(ESI+) m/z 351 (M+H)+
실시예 265: N-(4-(1-(4- 시아노부타노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(4-cyanobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00365
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.37 - 7.30 (m, 1H), 6.56 (dd, J = 1.9, 3.5 Hz, 1H), 6.33 (d, J = 17.7 Hz, 1H), 4.20 (dd, J = 3.2, 15.0 Hz, 2H), 3.70 (dt, J = 5.6, 18.5 Hz, 2H), 2.64 - 2.52 (m, 6H), 2.01 (q, J = 3.1, 3.7 Hz, 1H), 1.84 (p, J = 7.4 Hz, 2H), 0.86 - 0.77 (m, 4H)
MS(ESI+) m/z 378 (M+H)+
실시예 266: N-(4-(1-아크릴로일-1,2,3,6- 테트라히드로피리딘 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-acryloyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00366
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.87 (s, 1H), 7.34 (t, J = 3.0 Hz, 1H), 6.98 - 6.76 (m, 1H), 6.56 (s, 1H), 6.34 (d, J = 24.5 Hz, 1H), 6.16 (d, J = 16.6 Hz, 1H), 5.72 (d, J = 10.2 Hz, 1H), 4.30 (d, J = 40.6 Hz, 2H), 3.85 - 3.74 (m, 2H), 2.61 (s, 2H), 2.02 (s, 1H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 337 (M+H)+
실시예 267: N-(4-(1-(( 1S,2S )-2- 시아노시클로프로판 -1- 카보닐 )-1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]-6-일)시클로프로판카르복사미드 (N-(4-(1-((1S,2S)-2-cyanocyclopropane-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00367
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.54 (s, 1H), 7.88 (s, 1H), 7.35 (s, 1H), 6.57 (d, J = 2.4 Hz, 1H), 6.35 (s, 1H), 4.50 (d, J = 3.2 Hz, 1H), 4.19 (s, 1H), 4.00 - 3.87 (m, 1H), 3.83 - 3.64 (m, 1H), 3.03 - 2.80 (m, 1H), 2.10 (dt, J = 5.2, 9.7 Hz, 1H), 2.02 (s, 1H), 1.45 (s, 1H), 1.35 (d, J = 4.1 Hz, 1H), 0.86 - 0.73 (m, 4H)
MS(ESI+) m/z 376 (M+H)+
실시예 268: N-(4-(1-(2-(1- 시아노시클로프로필 )아세틸)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-(1-cyanocyclopropyl)acetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00368
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.34 (t, J = 3.0 Hz, 1H), 6.56 (d, J = 4.1 Hz, 1H), 6.32 (d, J = 37.2 Hz, 1H), 4.21 (s, 1H), 4.14 (s, 1H), 3.74 (t, J = 5.6 Hz, 1H), 3.59 (t, J = 4.9 Hz, 1H), 2.79 (s, 1H), 2.74 (s, 1H), 2.61 (s, 1H), 2.05 - 1.96 (m, 2H), 1.18 (s, 1H), 0.94 (dd, J = 7.3, 4.8 Hz, 2H), 0.89 - 0.74 (m, 5H)
MS(ESI+) m/z 390 (M+H)+
실시예 269: N-(4-(1-(2- 시아노프로파노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanopropanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00369
MS(ESI+) m/z 364 (M+H)+
실시예 270: N-(4-(1-( 부트 -3- 에노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(but-3-enoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00370
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.57 (s, 1H), 7.84 (s, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.56 (d, J = 2.7 Hz, 1H), 6.34 (d, J = 23.8 Hz, 1H), 6.02 - 5.85 (m, 1H), 5.15 - 5.08 (m, 2H), 4.25-4.14 (m, 2H), 3.24 (dd, J = 18.3, 6.7 Hz, 2H), 3.02 (d, J = 6.7 Hz, 1H), 2.69 (s, 2H), 2.06 - 1.95 (m, 2H), 0.86 - 0.78 (m, 4H)
MS(ESI+) m/z 351 (M+H)+
실시예 271: N-(4-(1-(2- 시아노부타노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00371
MS(ESI+) m/z 378 (M+H)+
실시예 272: N-(4-(1-(2,2,2- 트리플루오로아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,2,2-trifluoroacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide) 의 합성
Figure pat00372
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 7.88 (s, 1H), 7.36 (t, J = 3.0 Hz, 1H), 6.57 (td, J = 1.8, 3.5 Hz, 1H), 6.46 - 6.31 (m, 1H), 4.42 - 4.28 (m, 2H), 3.85 (dt, J = 5.6, 10.9 Hz, 2H), 2.66 (d, J = 15.5 Hz, 2H), 2.02 (ddd, J = 3.4, 7.5, 14.4 Hz, 1H), 0.83-0.70 (m, 4H).
MS(ESI+) m/z 379 (M+H)+
실시예 273: N-(4-(1-(2- 메틸시클로프로판 -1-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-methylcyclopropane-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00373
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.56 (s, 1H), 7.88 (s, 1H), 7.40 - 7.26 (m, 1H), 6.56 (dd, J = 1.9, 3.6 Hz, 1H), 6.35 (s, 1H), 4.44 (s, 1H), 4.16 (s, 1H), 3.90 (s, 1H), 3.70 (s, 1H), 2.65 (d, J = 12.4 Hz, 1H), 2.02 (s, 1H), 1.77 (d, J = 49.4 Hz, 1H), 1.26 - 1.09 (m, 5H), 0.95 (d, J = 6.2 Hz, 1H), 0.83 - 0.76 (m, 4H)
MS(ESI+) m/z 365 (M+H)+
실시예 274: N-(4-(1-(-2- 플루오로사이클로프로판 -1- 카보닐 )-1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-fluorocyclopropane-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00374
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.54 (s, 1H), 7.86 (s, 1H), 7.33 (t, J = 3.0 Hz, 1H), 6.55 (t, J = 2.7 Hz, 1H), 6.33 (s, 1H), 4.74 (d, J = 5.4 Hz, 1H), 4.46 (s, 1H), 4.15 (s, 1H), 3.92 (s, 1H), 3.78 - 3.58 (m, 1H), 2.71 - 2.61 (m, 2H), 2.00 (s, 1H), 1.43 (s, 1H), 1.18 (dt, J = 7.0, 13.0 Hz, 1H), 0.84 - 0.73 (m, 4H)
MS(ESI+) m/z 369 (M+H)+
실시예 275: 4 -(1-(2- 시아노아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘7-옥사이드 (4-(1-(2-cyanoacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridine 7- oxide )의 합성
Figure pat00375
MS(ESI+) m/z 366 (M+H)+
실시예 276: N-(4-(1-(2-(3,4- 디플루오로페닐 )아세틸)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]사이클로프로판 카르복사미드 (N-(4-(1-(2-(3,4-difluorophenyl)acetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00376
1H NMR (400 MHz, Methanol-d4) δ 11.45 (s, 1H), 10.56 (s, 1H), 7.87 (s, 1H), 7.42 - 7.30 (m, 3H), 7.10 (s, 1H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 6.33 (d, J = 21.7 Hz, 1H), 4.30 (s, 1H), 4.20 (s, 1H), 3.82 (d, J = 17.6 Hz, 2H), 3.75 (t, J = 6.4 Hz, 2H), 2.68 (d, J = 7.4 Hz, 2H), 2.02 (s, 1H), 0.87 - 0.76 (m, 4H)
MS(ESI+) m/z 437 (M+H)+
실시예 277: N-(4-(1- 이소니코티노일 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-isonicotinoyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00377
1H NMR (400 MHz, Methanol-d4) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.70 (d, J = 5.1 Hz, 2H), 7.88 (s, 1H), 7.53 - 7.43 (m, 2H), 7.35 (d, J = 11.1 Hz, 1H), 6.64 - 6.51 (m, 1H), 6.32 (d, J = 82.1 Hz, 1H), 4.36 (s, 1H), 4.08 (s, 1H), 3.91 (s, 1H), 3.51 (s, 1H), 2.63 (s, 2H), 2.02 (s, 1H), 0.85 - 0.74 (m, 4H)
MS(ESI+) m/z 388 (M+H)+
실시예 278: N-(4-(1-(푸란-3-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(furan-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00378
1H NMR (400 MHz, Methanol-d4) δ 11.45 (s, 1H), 10.56 (s, 1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.80 - 7.72 (m, 1H), 7.43 - 7.27 (m, 1H), 6.76 (d, J = 1.9 Hz, 1H), 6.59 (s, 1H), 6.36 (s, 1H), 4.32 (s, 2H), 3.81 (s, 2H), 2.68 (d, J = 7.1 Hz, 2H), 2.01 (d, J = 8.1 Hz, 1H), 0.83 - 0.75 (m, 4H)
MS(ESI+) m/z 377 (M+H)+
실시예 279: N-(4-(1-(4- 플루오로벤조일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(4-fluorobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00379
1H NMR (400 MHz, Methanol-d4) δ 11.45 (s, 1H), 10.56 (s, 1H), 7.88 (s, 1H), 7.57 (dd, J = 5.5, 8.5 Hz, 2H), 7.38 - 7.19 (m, 3H), 6.59 (s, 1H), 6.42 (s, 1H), 4.24 (d, J = 60.2 Hz, 2H), 3.68 - 3.52 (m, 2H), 2.66 (d, J = 24.6 Hz, 2H), 2.01 (s, 1H), 0.83 - 0.71 (m, 4H)
MS(ESI+) m/z 405 (M+H)+
실시예 280: N-(4-(1-(1- 메틸피롤리딘 -3-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-시클로프로판카르복사미드 (N-(4-(1-(1-methylpyrrolidine-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00380
1H NMR (400 MHz, Methanol-d4) δ 11.45 (s, 1H), 10.55 (s, 1H), 7.86 (s, 1H), 7.35 (s, 1H), 6.56 (s, 1H), 6.34 (d, J = 24.0 Hz, 1H), 4.22 (d, J = 32.6 Hz, 2H), 3.71 (d, J = 5.4 Hz, 2H), 2.67 (s, 2H), 2.36 - 2.21 (m, 4H), 2.00 (s, 3H), 0.88 - 0.71 (m, 4H)
MS(ESI+) m/z 394 (M+H)+
실시예 281: N-(4-(1-( 디메틸글리실 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(dimethylglycyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00381
1H NMR (400 MHz, Methanol-d4) δ 11.47 (s, 1H), 10.57 (s, 1H), 7.88 (d, J = 4.4 Hz, 1H), 7.36 (s, 1H), 6.56 (d, J = 3.6 Hz, 1H), 6.40 - 6.28 (m, 1H), 4.20 (d, J = 37.1 Hz, 4H), 3.78 (s, 1H), 3.60 (s, 1H), 2.77 (s, 6H), 2.62 (d, J = 36.3 Hz, 3H), 2.05 - 1.97 (m, 1H), 0.79 (s, 4H)
MS(ESI+) m/z 368 (M+H)+
실시예 282: N-(4-(1-(2-(트리플루오로메틸)시클로프로판-1-카르보닐)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-(trifluoromethyl)cyclopropane-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00382
1H NMR (400 MHz, Methanol-d4) δ 11.45 (s, 1H), 10.55 (s, 1H), 7.87 (s, 1H), 7.35 (s, 1H), 6.56 (s, 1H), 6.34 (s, 1H), 4.47 (d, J = 16.4 Hz, 1H), 4.20 (s, 1H), 3.92 (s, 1H), 3.64 (s, 2H), 2.67 - 2.61 (m, 2H), 2.26 (s, 1H), 2.01 (s, 1H), 0.78 (d, J = 9.3 Hz, 4H)
MS(ESI+) m/z 419 (M+H)+
실시예 283: N-(4-(1-(2- 시아노아세틸 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00383
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.57 (s, 1H), 7.84 (d, J = 10.2 Hz, 1H), 7.34 (d, J = 3.1 Hz, 1H), 6.48 (dd, J = 1.8, 3.7 Hz, 1H), 6.17 - 6.03 (m, 1H), 4.31 - 4.01 (m, 6H), 3.96 - 3.62 (m, 2H), 3.02 (m J = 36.6 Hz, 1H), 2.02 (s, 1H), 0.88 (s, 3H), 0.84 - 0.73 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 284: N-(4-(1-(3- 시아노프로파노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-시클로프로판카르복사미드 (N-(4-(1-(3-cyanopropanoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00384
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.56 (s, 1H), 7.85 (d, J = 5.5 Hz, 1H), 7.34 (d, J = 3.5 Hz, 1H), 6.49 (dt, J = 2.0, 3.5 Hz, 1H), 6.11 (d, J = 15.7 Hz, 1H), 4.31 (d, J = 24.5 Hz, 1H), 4.14 - 3.90 (m, 2H), 3.57 (d, J = 4.5 Hz, 2H), 3.00 (d, J = 27.7 Hz, 2H), 2.85 (dd, J = 7.7, 15.5 Hz, 4H), 2.02 (s, 1H), 0.88 (d, J = 10.7 Hz, 3H), 0.82 - 0.76 (m, 4H)
MS(ESI+) m/z 378 (M+H)+
실시예 285: N-(4-(1-(4- 시아노부타노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-시클로프로판카르복사미드 (N-(4-(1-(4-cyanobutanoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00385
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.56 (s, 1H), 7.84 (d, J = 5.1 Hz, 1H), 7.33 (s, 1H), 6.49 (s, 1H), 6.11 (d, J = 10.4 Hz, 1H), 4.44 - 4.24 (m, 1H), 3.93 (d, J = 17.1 Hz, 1H), 3.66 - 3.56 (m, 2H), 2.98 (d, J = 26.6 Hz, 1H), 2.68 (s, 4H), 2.04 (d, J = 19.1 Hz, 1H), 1.84 (p, J = 6.3, 6.9 Hz, 2H), 0.93 - 0.84 (m, 3H), 0.83 - 0.71 (m, 4H)
MS(ESI+) m/z 392 (M+H)+
실시예 286: N-(4-(1-(1,2,5- 옥사디아졸 -3-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-시클로프로판카르복사미드 (N-(4-(1-(1,2,5-oxadiazole-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00386
1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.57 (s, 1H), 9.32 (d, J = 10.0 Hz, 1H), 7.89 (s, 1H), 7.36 (dt, J = 6.3, 3.2 Hz, 1H), 6.57 (ddd, J = 8.5, 3.6, 1.9 Hz, 1H), 6.36 (d, J = 47.7 Hz, 1H), 4.42 (d, J = 3.9 Hz, 2H), 3.96 (t, J = 5.6 Hz, 1H), 3.84 (t, J = 5.6 Hz, 1H), 2.68 (d, J = 6.7 Hz, 2H), 2.04 - 1.99 (m, 1H), 0.82 - 0.75 (m, 4H)
MS(ESI+) m/z 379 (M+H)+
실시예 287: N-(4-(1-( 이소옥사졸 -4-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(isoxazole-4-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00387
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 9.46 (s, 1H), 8.94 (s, 1H), 7.89 (s, 1H), 7.36 (s, 1H), 6.58 (d, J = 18.3 Hz, 1H), 6.34 (d, J = 47.3 Hz, 1H), 4.35 (d, J = 34.0 Hz, 2H), 3.81 (d, J = 39.9 Hz, 2H), 2.73 (s, 1H), 2.61 (s, 1H), 2.00 (d, J = 13.2 Hz, 1H), 0.85 - 0.74 (m, 4H)
MS(ESI+) m/z 378 (M+H)+
실시예 288: N-(4-(1-( 이소옥사졸 -5-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(isoxazole-5-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00388
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.79 (t, J = 2.9 Hz, 1H), 7.89 (d, J = 4.7 Hz, 1H), 7.36 (s, 1H), 7.07 - 7.00 (m, 1H), 6.58 (d, J = 13.4 Hz, 1H), 6.35 (d, J = 45.2 Hz, 1H), 4.36 (s, 2H), 3.91 (s, 1H), 3.75 (d, J = 6.0 Hz, 1H), 2.70 (s, 1H), 2.64 (s, 1H), 2.00 (d, J = 9.2 Hz, 1H), 0.85-0.76 (m, 4H)
MS(ESI+) m/z 378 (M+H)+
실시예 289: N-(4-(1-(2- 시아노아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-5-메틸-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00389
1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 10.12 (s, 1H), 7.37 (t, J = 2.9 Hz, 1H), 6.31 (s, 1H), 5.69 (d, J = 7.0 Hz, 1H), 4.20 - 4.07 (m, 4H), 3.62 (t, J = 5.8 Hz, 2H), 2.42 (s, 1H), 2.37-2.26 (m, 1H), 2.11 (s, 3H), 1.92 - 1.80 (m, 1H), 0.79 (d, J = 6.0 Hz, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 290: N-(5- 메틸 -4-(1-(3,3,3- 트리플루오로프로파노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-시클로프로판카르복사미드 (N-(5-methyl-4-(1-(3,3,3-trifluoropropanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00390
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.04 (s, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.26 (d, J = 2.5 Hz, 1H), 5.68 (d, J = 6.8 Hz, 1H), 4.26 - 4.12 (m, 2H), 3.84 - 3.66 (m, 4H), 2.41 (s, 1H), 2.30 (s, 1H), 2.09 (s, 3H), 1.83 (q, J = 6.3 Hz, 1H), 0.76 (d, J = 6.2 Hz, 4H)
MS(ESI+) m/z 407 (M+H)+
실시예 291: N-(4-(1-(티아졸-4-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(thiazole-4-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00391
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.56 (s, 1H), 9.22 (s, 1H), 8.24 (d, J = 2.0 Hz, 1H), 7.89 (s, 1H), 7.35 (s, 1H), 6.57 (d, J = 14.9 Hz, 1H), 6.37 (d, J = 60.7 Hz, 1H), 4.40 (d, J = 35.2 Hz, 2H), 3.88 (d, J = 19.6 Hz, 2H), 2.65 (s, 2H), 2.01 (d, J = 5.7 Hz, 1H), 1.24 (m, 2H), 0.80 (m, 2H)
MS(ESI+) m/z 394 (M+H)+
실시예 292: N-(4-(1-( 이소티아졸 -4-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(isothiazole-4-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00392
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.65 (d, J = 1.8 Hz, 1H), 7.89 (s, 1H), 7.77 (s, 1H), 7.35 (s, 1H), 6.60 (s, 1H), 6.35 (d, J = 53.1 Hz, 1H), 4.36 (d, J = 3.1 Hz, 2H), 3.91 (s, 1H), 3.74 (s, 1H), 2.71 - 2.65 (m, 2H), 2.02 (dd, J = 8.9, 4.0 Hz, 1H), 1.25 (m, 2H), 0.87 - 0.73 (m, 2H)
MS(ESI+) m/z 394 (M+H)+
실시예 293: N-(4-(1-(4- 시아노벤조일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(4-cyanobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00393
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.56 (s, 1H), 7.96 (d, J = 7.8 Hz, 2H), 7.88 (s, 1H), 7.69 (d, J = 7.9 Hz, 2H), 7.36 (s, 1H), 6.57 (d, J = 30.7 Hz, 1H), 6.32 (d, J = 87.2 Hz, 1H), 4.35 (s, 1H), 3.99 (d, J = 68.8 Hz, 2H), 3.50 (s, 1H), 2.62 (s, 2H), 2.04 - 1.96 (m, 1H), 0.80 (d, J = 5.2 Hz, 4H)
MS(ESI+) m/z 412 (M+H)+
실시예 294: N-(4-(1-(2- 시아노아세틸 )-3-에틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-3-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00394
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.56 (s, 1H), 7.83 (d, J = 10.8 Hz, 1H), 7.34 (s, 1H), 6.48 (d, J = 3.2 Hz, 1H), 6.10 (d, J = 22.6 Hz, 1H), 4.34 - 4.19 (m, 2H), 4.04 (dd, J = 9.2, 18.5 Hz, 2H), 3.62 - 3.57 (m, 1H), 2.76 (s, 1H), 2.00 (d, J = 12.4 Hz, 1H), 1.28 (s, 2H), 1.03 (d, J = 6.2 Hz, 3H), 0.87 - 0.73 (m, 7H)
MS(ESI+) m/z 378 (M+H)+
실시예 295: N-(4-(1-(3- 시아노프로파노일 )-3-에틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-cyanopropanoyl)-3-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00395
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.56 (s, 1H), 7.84 (d, J = 5.5 Hz, 1H), 7.33 (s, 1H), 6.49 (d, J = 2.9 Hz, 1H), 6.13 (d, J = 23.5 Hz, 1H), 4.50 - 4.26 (m, 2H), 3.98 (dd, J = 19.2, 50.3 Hz, 1H), 3.76 - 3.48 (m, 3H), 2.87 (s, 2H), 2.73 (d, J = 6.4 Hz, 2H), 2.00 (d, J = 12.8 Hz, 1H), 1.36 - 1.14 (m, 3H), 0.98 - 0.68 (m, 7H)
MS(ESI+) m/z 392 (M+H)+
실시예 296: N-(4-(1-(2- 시아노아세틸 )-5- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-5-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00396
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.57 (s, 1H), 7.67 (s, 1H), 7.31 (t, J = 3.0 Hz, 1H), 6.24 (tt, J = 1.5, 3.3 Hz, 1H), 4.14 (dd, J = 1.2, 3.5 Hz, 2H), 4.07 - 3.94 (m, 2H), 3.70 (t, J = 5.7 Hz, 1H), 3.57 (t, J = 5.7 Hz, 1H), 2.34 (s, 1H), 2.05 - 1.95 (m, 1H), 1.52 (s, 3H), 1.24 (d, J = 8.3 Hz, 1H), 0.83 - 0.75 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 297: N-(4-(1-(2- 브로모아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-bromoacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00397
MS(ESI+) m/z 404 (M+H)+
실시예 298: N-(4-(1-(2- 클로로아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-chloroacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00398
MS(ESI+) m/z 359, 361 (M+H)+
실시예 299: N-(4-(1-(2- 시아노아세틸 )-3,3-디메틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-3,3-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00399
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.56 (s, 1H), 7.73 (d, J = 7.5 Hz, 1H), 7.28 (s, 1H), 6.30 (s, 1H), 5.67 - 5.54 (m, 1H), 4.19 - 4.06 (m, 4H), 3.48 (s, 2H), 2.01 (s, 1H), 1.01 (dd, J = 3.7, 13.5 Hz, 6H), 0.80 (d, J = 5.3 Hz, 4H)
MS(ESI+) m/z 378 (M+H)+
실시예 300: N-(4-(1-(3- 시아노프로파노일 )-3,3-디메틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-cyanopropanoyl)-3,3-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00400
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.56 (s, 1H), 7.74 (d, J = 8.2 Hz, 1H), 7.28 (s, 1H), 6.34 - 6.24 (m, 1H), 5.60 (d, J = 10.1 Hz, 1H), 4.13 (dd, J = 3.3, 14.9 Hz, 2H), 3.50 - 3.44 (m, 2H), 2.82 (d, J = 3.8 Hz, 2H), 2.67 (d, J = 4.4 Hz, 2H), 2.01 (s, 1H), 1.03 (s, 3H), 0.99 (s, 3H), 0.81 - 0.74 (m, 4H)
MS(ESI+) m/z 392 (M+H)+
실시예 301: N-(4-(1-(2- 시아노아세틸 )-1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)퓨란-2-카르복사미드 (N-(4-(1-(2-cyanoacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)furan-2-carboxamide)의 합성
Figure pat00401
MS(ESI+) m/z 376 (M+H)+
실시예 302: N-(4-(5-(3- 시아노프로파노일 )-5- 아자스피로[2.5]옥트 -7-엔-8-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(5-(3-cyanopropanoyl)-5-azaspiro[2.5]oct-7-en-8-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00402
1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.59 - 10.52 (m, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.30 (q, J = 3.0 Hz, 1H), 6.27 (ddd, J = 10.1, 3.5, 1.9 Hz, 1H), 5.69 (dt, J = 7.0, 3.3 Hz, 1H), 4.23 (dd, J = 11.8, 3.2 Hz, 2H), 3.63 (dt, J = 6.6, 3.3 Hz, 2H), 3.57 (d, J = 19.1 Hz, 2H), 3.21 - 3.09 (m, 2H), 2.81 (dt, J = 23.9, 6.8 Hz, 2H), 2.67 (t, J = 6.3 Hz, 2H), 2.00 (d, J = 7.2 Hz, 1H), 0.81 - 0.76 (m, 4H)
MS(ESI+) m/z 390 (M+H)+
실시예 303: N-(4-(5-(2- 시아노아세틸 )-5- 아자스피로[2.5]옥트 -7-엔-8-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(5-(2-cyanoacetyl)-5-azaspiro[2.5]oct-7-en-8-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00403
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.53 (s, 1H), 7.86 (d, J = 2.4 Hz, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.55 (dd, J = 3.5, 1.8 Hz, 1H), 6.31 (d, J = 26.1 Hz, 1H), 4.21 - 4.17 (m, 1H), 4.13 (d, J = 23.2 Hz, 3H), 3.72 (t, J = 5.6 Hz, 1H), 3.59 (t, J = 5.5 Hz, 1H), 2.64 (s, 2H), 2.55 (s, 1H), 2.01 (d, J = 4.8 Hz, 1H), 0.83 - 0.77 (m, 4H)
MS(ESI+) m/z 376 (M+H)+
실시예 304: (S)-N-(4-(1-(2- 시아노아세틸 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-cyanoacetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00404
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.57 (s, 1H), 7.84 (d, J = 10.2 Hz, 1H), 7.34 (d, J = 3.1 Hz, 1H), 6.48 (dd, J = 1.8, 3.7 Hz, 1H), 6.17 - 6.03 (m, 1H), 4.31 - 4.01 (m, 6H), 3.96 - 3.62 (m, 2H), 3.02 (m J = 36.6 Hz, 1H), 2.02 (s, 1H), 0.88 (s, 3H), 0.84 - 0.73 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 305: (R)-N-(4-(1-(2- 시아노아세틸 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((R)-N-(4-(1-(2-cyanoacetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00405
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.57 (s, 1H), 7.84 (d, J = 10.2 Hz, 1H), 7.34 (d, J = 3.1 Hz, 1H), 6.48 (dd, J = 1.8, 3.7 Hz, 1H), 6.17 - 6.03 (m, 1H), 4.31 - 4.01 (m, 6H), 3.96 - 3.62 (m, 2H), 3.02 (m J = 36.6 Hz, 1H), 2.02 (s, 1H), 0.88 (s, 3H), 0.84 - 0.73 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 306: N-(4-(3- 메틸 -1-(2- 메틸티아졸 -5-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(2-methylthiazole-5-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00406
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.03 (s, 1H), 7.85 (s, 1H), 7.33 (d, J = 3.5 Hz, 1H), 6.51 (s, 1H), 6.12 (s, 1H), 4.51 (d, J = 18.2 Hz, 1H), 4.25 (s, 1H), 3.83 (s, 2H), 3.07 (s, 1H), 2.70 (d, J = 2.8 Hz, 3H), 2.01 (d, J = 8.8 Hz, 1H), 0.90 (d, J = 6.7 Hz, 3H), 0.86-0.74 (m, 4H)
MS(ESI+) m/z 422 (M+H)+
실시예 307: N-(4-(1-(2,4-디메틸티아졸-5-카르보닐)-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,4-dimethylthiazole-5-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00407
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 7.83 (s, 1H), 6.48 (s, 1H), 6.11 (s, 1H), 4.41 (s, 1H), 4.09 (d, J = 18.6 Hz, 1H), 3.66 (s, 2H), 3.01 (s, 1H), 2.64 (d, J = 3.3 Hz, 3H), 2.32 (d, J = 3.4 Hz, 3H), 2.02 (s, 1H), 0.86 (d, J = 6.5 Hz, 3H), 0.78 (d, J = 9.6 Hz, 4H)
MS(ESI+) m/z 436 (M+H)+
실시예 308: N-(4-(3- 메틸 -1-(4- 메틸티아졸 -5-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(4-methylthiazole-5-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00408
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 9.12 (d, J = 2.1 Hz, 1H), 7.84 (d, J = 2.6 Hz, 1H), 7.33 (q, J = 2.9 Hz, 1H), 6.48 (dt, J = 4.2, 2.0 Hz, 1H), 6.12 (s, 1H), 4.51 (s, 1H), 4.09 (d, J = 18.1 Hz, 1H), 3.74 - 3.59 (m, 1H), 3.01 (s, 1H), 2.41 (d, J = 2.3 Hz, 3H), 2.02 (tt, J = 8.8, 5.2 Hz, 1H), 0.94 - 0.83 (m, 3H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 422 (M+H)+
실시예 309: N-(4-(1-(2- 플루오로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-fluoroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00409
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.37 (d, J = 5.1 Hz, 1H), 7.83 (d, J = 11.6 Hz, 1H), 7.44 (s, 1H), 7.33 (s, 2H), 6.50 (d, J = 14.2 Hz, 1H), 6.08 (d, J = 71.4 Hz, 1H), 4.54 (d, J = 19.5 Hz, 1H), 4.11 (d, J = 49.6 Hz, 2H), 3.60 (d, J = 13.1 Hz, 1H), 2.02 (s, 1H), 0.95 (d, J = 6.8 Hz, 1H), 0.84 - 0.73 (m, 6H)
MS(ESI+) m/z 420 (M+H)+
실시예 310: N-(4-(1-(2- 클로로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-chloroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00410
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 7.83 (d, J = 12.1 Hz, 1H), 7.65 (d, J = 7.4 Hz, 1H), 7.51 (s, 1H), 7.32 (d, J = 8.5 Hz, 1H), 6.50 (d, J = 11.5 Hz, 1H), 6.08 (d, J = 67.3 Hz, 1H), 4.58 - 4.10 (m, 1H), 4.05 (s, 1H), 3.60 (d, J = 12.9 Hz, 1H), 3.02 (d, J = 41.1 Hz, 1H), 2.01 (s, 1H), 0.94 (d, J = 6.6 Hz, 1H), 0.86 - 0.74 (m, 6H).
MS(ESI+) m/z 436, 438 (M+H)+
실시예 311: N-(4-(1-(3,4- 디플루오로벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3,4-difluorobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00411
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.67 - 7.49 (m, 3H), 7.33 (s, 2H), 6.50 (s, 1H), 4.12 (s, 2H), 3.63 (d, J = 12.5 Hz, 1H), 3.01 (s, 1H), 2.01 (s, 1H), 0.92 (s, 1H), 0.86 - 0.74 (m, 6H).
MS(ESI+) m/z 437 (M+H)+
실시예 312: N-(4-(1-(3- 플루오로 -4- 메톡시벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-fluoro-4-methoxybenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00412
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.39 - 7.23 (m, 4H), 6.49 (s, 1H), 6.10 (s, 1H), 4.13 (d, J = 18.7 Hz, 1H), 3.65 (d, J = 11.9 Hz, 1H), 3.02 (s, 1H), 2.02 (s, 1H), 0.92 - 0. 68 (m, 7H).
MS(ESI+) m/z 449 (M+H)+
실시예 313: N-(4-(3- 메틸 -1-(1H-피롤-2-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(1H-pyrrole-2-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00413
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 11.42 (s, 1H), 10.55 (s, 1H), 7.86 (s, 1H), 7.32 (s, 1H), 6.91 (s, 1H), 6.62 (s, 1H), 6.56 - 6.47 (m, 1H), 6.16 (s, 2H), 4.59 (d, J = 19.0 Hz, 1H), 4.30 (d, J = 19.2 Hz, 1H), 4.08 - 3.96 (m, 1H), 3.06 (s, 1H), 2.02 (s, 1H), 0.92 (d, J = 6.7 Hz, 3H), 0.79 (s, 4H)
MS(ESI+) m/z 390 (M+H)+
실시예 314: N-(4-(1-(3- 플루오로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-fluoroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00414
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.74 (s, 1H), 8.62 - 8.47 (m, 1H), 7.84 (d, J = 14.4 Hz, 1H), 7.57 (d, J = 5.3 Hz, 1H), 7.34 (d, J = 5.1 Hz, 1H), 6.49 (d, J = 10.0 Hz, 1H), 6.09 (d, J = 71.3 Hz, 1H), 4.17 (t, J = 19.7 Hz, 1H), 3.99 (s, 1H), 3.60 (d, J = 13.8 Hz, 1H), 3.01 (d, J = 56.3 Hz, 1H), 2.02 (s, 1H), 0.95 (d, J = 6.8 Hz, 1H), 0.79 (d, J = 7.4 Hz, 6H)
MS(ESI+) m/z 420 (M+H)+
실시예 315: N-(4-(1-(3-(2-(3,5-디옥소모르폴리노)에틸)벤조일)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(2-(3,5-dioxomorpholino)ethyl)benzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00415
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.81 (d, J = 17.3 Hz, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.30 (d, J = 9.5 Hz, 4H), 6.50 (s, 1H), 6.09 (d, J = 71.6 Hz, 1H), 4.05 (d, J = 28.5 Hz, 2H), 3.91 (t, J = 7.4 Hz, 3H), 3.62 (dd, J = 13.1, 4.2 Hz, 1H), 3.38 (q, J = 7.0 Hz, 2H), 2.98 (s, 1H), 2.84 (t, J = 7.4 Hz, 2H), 2.01 (d, J = 5.1 Hz, 1H), 1.09 (t, J = 7.0 Hz, 2H), 0.93 (s, 1H), 0.89 - 0.69 (m, 7H)
MS(ESI+) m/z 542 (M+H)+
실시예 316: N-(4-(3- 메틸 -1-(3-( 페닐아미노 ) 벤조일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판 카르복사미드 (N-(4-(3-methyl-1-(3-(phenylamino)benzoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00416
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.55 (s, 1H), 9.20 (s, 1H), 8.18 (d, J = 4.9 Hz, 1H), 7.84 (s, 1H), 7.58 (ddd, J = 8.7, 7.1, 2.0 Hz, 1H), 7.37 - 7.29 (m, 2H), 6.94 (d, J = 7.6 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 6.76 (dd, J = 7.0, 4.9 Hz, 1H), 6.49 (s, 1H), 4.46 (s, 1H), 4.27 - 4.05 (m, 2H), 3.67 (s, 1H), 3.04 (s, 1H), 2.02 (s, 1H), 0.88 - 0.69 (m, 7H)
MS(ESI+) m/z 492 (M+H)+
실시예 317: N-(4-(1-(6-(2,4-디플루오로페닐)-2-옥소-1,2-디히드로피리딘-3-카르보닐)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일}-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(6-(2,4-difluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00417
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 8.37 (d, J = 7.5 Hz, 1H), 7.84 - 7.75 (m, 2H), 7.52 - 7.41 (m, 2H), 7.36 - 7.20 (m, 3H), 6.88 (dd, J = 7.6, 1.5 Hz, 1H), 4.20 - 4.05 (m, 1H), 4.01 (p, J = 6.6 Hz, 1H), 3.49 (dt, J = 14.8, 6.9 Hz, 1H), 3.15 (q, J = 9.1 Hz, 1H), 2.07 - 1.99 (m, 1H), 1.94 (q, J = 12.1, 10.2 Hz, 1H), 1.25 - 1.17 (m, 3H), 0.81 (td, J = 14.7, 12.6, 5.0 Hz, 4H)
MS(ESI+) m/z 530 (M+H)+
실시예 318: 메틸1-(4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-3-메틸-1,2,3,6-테트라히드로피리딘-1-카르보닐)시클로부탄-1-카르복실레이트 ( methyl 1-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methyl-1,2,3,6-tetrahydropyridine-1-carbonyl)cyclobutane-1-carboxylate)의 합성
Figure pat00418
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.54 (s, 1H), 7.82 (d, J = 3.4 Hz, 1H), 7.39 - 7.26 (m, 1H), 6.45 (d, J = 15.8 Hz, 1H), 6.06 (d, J = 43.3 Hz, 1H), 4.32 - 4.00 (m, 2H), 2.93 (s, 1H), 2.07 - 1.90 (m, 3H), 1.82 (s, 1H), 1.31 - 1.19 (m, 1H), 0.98 - 0.69 (m, 10H)
MS(ESI+) m/z 437 (M+H)+
실시예 319: 메틸1-(4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-3-메틸-1,2,3,6-테트라히드로피리딘-1-카르보닐)시클로프로판-1-카르복실레이트 ( methyl 1-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methyl-1,2,3,6-tetrahydropyridine-1-carbonyl)cyclopropane-1-carboxylate)의 합성
Figure pat00419
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.55 (s, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.41 - 7.26 (m, 1H), 6.48 (s, 1H), 6.11 (d, J = 6.0 Hz, 1H), 4.28 (t, J = 20.9 Hz, 2H), 4.06 (d, J = 15.8 Hz, 2H), 3.68 (d, J = 8.6 Hz, 5H), 2.99 (d, J = 27.0 Hz, 1H), 2.02 (s, 1H), 1.40 (q, J = 11.2, 7.4 Hz, 4H), 1.32 - 1.21 (m, 2H), 0.88 (t, J = 7.4 Hz, 4H), 0.84 - 0.74 (m, 4H)
MS(ESI+) m/z 423 (M+H)+
실시예 320: 메틸3 -(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-메틸-3,6-디히드로피리딘-1(2H)-일)-2-메틸-3-옥소프로파노에이트 (methyl 3-(4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3-b]pyridin -4- yl )-3-methyl-3,6-dihydropyridin-1(2H)-yl)-2-methyl-3-oxopropanoate)의 합성
Figure pat00420
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 7.85 (s, 1H), 7.34 (s, 1H), 6.48 (d, J = 8.4 Hz, 1H), 6.12 (d, J = 16.1 Hz, 1H), 4.21 - 3.97 (m, 6H), 3.68 (d, J = 19.0 Hz, 1H), 3.00 (s, 1H), 2.03 (s, 1H), 1.26 (dd, J = 7.6, 4.2 Hz, 4H), 0.87 - 0.74 (m, 7H)
MS(ESI+) m/z 411 (M+H)+
실시예 321: N-(4-(1-(6-(tert-부틸)-2-옥소-1,2-디히드로피리딘-3-카르보닐)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(6-(tert-butyl)-2-oxo-1,2-dihydropyridine-3-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00421
1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 11.41 (s, 1H), 10.54 (s, 1H), 7.83 (d, J = 12.1 Hz, 1H), 7.48 (t, J = 6.5 Hz, 1H), 7.36 - 7.25 (m, 1H), 6.48 (s, 1H), 6.09 (d, J = 37.7 Hz, 2H), 4.26 (dd, J = 94.3, 20.9 Hz, 1H), 4.05 (s, 1H), 3.60 - 3.41 (m, 1H), 3.26 (dd, J = 13.0, 5.2 Hz, 1H), 3.04 (d, J = 24.5 Hz, 1H), 2.00 (d, J = 13.7 Hz, 1H), 1.28 (s, 9H), 0.84 - 0.72 (m, 7H)
MS(ESI+) m/z 474 (M+H)+
실시예 322: N-(4-(1-(6-(4-플루오로페닐)-2-옥소-1,2-디히드로피리딘-3-카르보닐)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(6-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00422
1H NMR (400 MHz, DMSO-d6) δ 12.21 (s, 1H), 11.42 (s, 1H), 10.54 (s, 1H), 8.00 - 7.80 (m, 3H), 7.64 (d, J = 7.4 Hz, 1H), 7.35 (t, J = 8.6 Hz, 3H), 6.49 (t, J = 2.0 Hz, 1H), 6.10 (d, J = 44.8 Hz, 1H), 4.26 - 4.03 (m, 2H), 3.69 - 3.44 (m, 2H), 3.05 (s, 1H), 2.02 (s, 1H), 0.91 - 0.70 (m, 7H)
MS(ESI+) m/z 512 (M+H)+
실시예 323: N-(4-(1-(3-플루오로-4-((2-모르폴리노에틸)아미노)벤조일)-3-메틸-1,2,3,6-테트라하이드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-fluoro-4-((2-morpholinoethyl)amino)benzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00423
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.43 - 7.28 (m, 1H), 7.25 - 7.12 (m, 2H), 6.78 (t, J = 8.6 Hz, 1H), 6.56 - 6.44 (m, 1H), 6.10 (s, 1H), 5.64 (s, 1H), 4.42 - 4.07 (m, 2H), 3.69 (s, 2H), 3.64 - 3.52 (m, 4H), 3.26 (t, J = 6.2 Hz, 2H), 3.03 (s, 1H), 2.43 (s, 2H), 2.11 - 1.94 (m, 1H), 0.85 (d, J = 6.8 Hz, 4H), 0.83 - 0.74 (m, 4H).
MS(ESI+) m/z 547 (M+H)+
실시예 324: N-(4-(1-(5- 브로모니코틴일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(5-bromonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00424
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.82 (d, J = 2.4 Hz, 1H), 8.68 (d, J = 4.6 Hz, 1H), 8.22 (d, J = 8.6 Hz, 1H), 7.84 (d, J = 8.6 Hz, 1H), 7.33 (s, 1H), 6.50 (d, J = 12.8 Hz, 1H), 6.09 (d, J = 63.9 Hz, 1H), 4.16 (d, J = 15.0 Hz, 2H), 3.64 (s, 1H), 3.36 (d, J = 7.5 Hz, 1H), 3.04 (d, J = 25.2 Hz, 1H), 2.00 (d, J = 14.1 Hz, 1H), 0.89 - 0.71 (m, 7H).
MS(ESI+) m/z 480, 482 (M+H)+
실시예 325: N-(4-(1-(2,3-디히드로벤조[b][1,4]디옥신-6-카르보닐)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,3-dihydrobenzo[b][1,4]dioxine-6-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00425
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.82 (s, 1H), 7.35 - 7.25 (m, 1H), 7.00 - 6.88 (m, 3H), 6.49 (s, 1H), 6.10 (s, 1H), 4.27 (s, 4H), 4.17 - 4.04 (m, 1H), 3.72 - 3.57 (m, 1H), 3.00 (s, 1H), 2.01 (td, J = 7.8, 7.4, 3.7 Hz, 1H), 0.85 (s, 3H), 0.84 - 0.76 (m, 4H)
MS(ESI+) m/z 459 (M+H)+
실시예 326: N-(4-(1-( 벤조[d][1,3]다이옥솔 -5-카르보닐)-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(benzo[d][1,3]dioxole-5-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00426
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.54 (s, 1H), 7.82 (s, 1H), 7.32 (t, J = 3.0 Hz, 1H), 7.04 (s, 1H), 6.98 (d, J = 2.4 Hz, 2H), 6.49 (d, J = 3.4 Hz, 1H), 6.09 (s, 3H), 4.18 - 4.02 (m, 1H), 3.69 - 3.57 (m, 1H), 3.01 (s, 1H), 2.01 (td, J = 7.4, 3.6 Hz, 1H), 0.84 (s, 3H), 0.81 - 0.75 (m, 4H)
MS(ESI+) m/z 445 (M+H)+
실시예 327: N-(4-(1-(1H-인돌-6-카르보닐)-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1H-indole-6-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00427
1H NMR (400 MHz, DMSO-d6) δ 11.42 (d, J = 2.8 Hz, 1H), 11.31 (s, 1H), 10.55 (s, 1H), 7.88 - 7.82 (m, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.51 (d, J = 1.4 Hz, 1H), 7.47 (t, J = 2.7 Hz, 1H), 7.32 (t, J = 3.0 Hz, 1H), 7.10 (dd, J = 8.1, 1.5 Hz, 1H), 6.49 (t, J = 2.5 Hz, 2H), 6.12 (s, 1H), 4.22 - 4.11 (m, 1H), 3.75 - 3.65 (m, 1H), 3.03 (s, 1H), 2.02 (td, J = 8.6, 7.9, 4.2 Hz, 1H), 0.88 (s, 3H), 0.83 - 0.74 (m, 4H)
MS(ESI+) m/z 440 (M+H)+
실시예 328: N-(4-(3- 메틸 -1-(1H- 피롤로[2,3-b]피리딘 -4-카르보닐)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(1H-pyrrolo[2,3-b]pyridine-4-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00428
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.32 (t, J = 3.0 Hz, 1H), 7.10 - 6.96 (m, 3H), 6.49 (s, 1H), 6.11 (s, 1H), 4.13 (d, J = 18.8 Hz, 1H), 3.80 (d, J = 4.3 Hz, 6H), 3.66 (dd, J = 12.9, 4.2 Hz, 1H), 3.02 (s, 1H), 2.02 (dq, J = 8.6, 4.2, 3.3 Hz, 1H), 0.95 - 0.84 (m, 3H), 0.84 - 0.70 (m, 4H)
MS(ESI+) m/z 441 (M+H)+
실시예 329: N-(4-(1-(3,4- 디메톡시벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3,4-dimethoxybenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00429
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.39 (t, J = 7.9 Hz, 1H), 7.32 (s, 1H), 7.07 - 6.96 (m, 3H), 6.49 (s, 1H), 4.17 - 3.99 (m, 2H), 3.80 (s, 3H), 3.62 (dd, J = 13.0, 4.1 Hz, 1H), 2.98 (s, 1H), 2.06 - 1.98 (m, 1H), 0.92 (s, 1H), 0.86 - 0.72 (m, 6H)
MS(ESI+) m/z 461 (M+H)+
실시예 330: N-(4-(1-(3- 메톡시벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-methoxybenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00430
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.39 (t, J = 7.9 Hz, 1H), 7.32 (s, 1H), 7.06 - 7.01 (m, 2H), 6.99 (d, J = 4.8 Hz, 1H), 6.49 (s, 1H), 4.19 - 4.00 (m, 2H), 3.80 (s, 3H), 3.62 (dd, J = 13.0, 4.1 Hz, 1H), 2.98 (s, 1H), 2.02 (td, J = 7.7, 3.9 Hz, 1H), 0.92 (s, 1H), 0.86 - 0.74 (m, 6H)
MS(ESI+) m/z 431 (M+H)+
실시예 331: N-(4-(3- 메틸 -1-(4- 니트로벤조일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(4-nitrobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00431
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.32 (dd, J = 8.5, 6.1 Hz, 3H), 7.84 (d, J = 9.3 Hz, 1H), 7.75 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 9.2 Hz, 1H), 6.50 (d, J = 17.8 Hz, 1H), 6.09 (d, J = 79.2 Hz, 1H), 4.37 (dd, J = 155.6, 19.8 Hz, 1H), 4.13 - 3.94 (m, 2H), 3.62 (d, J = 11.6 Hz, 1H), 3.04 (d, J = 44.3 Hz, 1H), 2.02 (dq, J = 8.0, 3.9, 2.8 Hz, 1H), 0.95 (d, J = 6.8 Hz, 1H), 0.83 - 0.74 (m, 6H)
MS(ESI+) m/z 446 (M+H)+
실시예 332: N-(4-(1-(3- 아세틸벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-acetylbenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00432
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.55 (s, 1H), 8.08 - 8.03 (m, 1H), 8.01 (s, 1H), 7.84 (s, 1H), 7.74 (d, J = 7.5 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.32 (s, 1H), 6.50 (s, 1H), 6.10 (d, J = 74.1 Hz, 1H), 4.65 - 4.15 (m, 1H), 4.08 (d, J = 33.0 Hz, 1H), 3.64 (d, J = 13.1 Hz, 1H), 3.03 (d, J = 33.6 Hz, 1H), 2.63 (d, J = 1.4 Hz, 3H), 2.02 (dd, J = 8.6, 4.2 Hz, 1H), 0.95 (s, 1H), 0.85 - 0.73 (m, 6H)
MS(ESI+) m/z 443 (M+H)+
실시예 333: N-(4-(1-(4- 클로로벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(4-chlorobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00433
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.53 (t, J = 9.6 Hz, 4H), 7.32 (s, 1H), 6.50 (s, 1H), 6.09 (d, J = 63.6 Hz, 1H), 4.52 (d, J = 19.2 Hz, 1H), 4.10 (s, 1H), 3.63 (dd, J = 13.0, 4.2 Hz, 1H), 3.00 (s, 1H), 2.06 - 1.97 (m, 1H), 0.92 (s, 1H), 0.82 - 0.75 (m, 6H)
MS(ESI+) m/z 435, 437 (M+H)+
실시예 334: N-(4-(1-(3- 브로모벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-bromobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00434
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.68 (d, J = 11.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.32 (s, 1H), 6.50 (s, 1H), 6.09 (d, J = 61.5 Hz, 1H), 4.55 (d, J = 19.7 Hz, 1H), 4.09 (s, 1H), 3.68 - 3.55 (m, 1H), 3.01 (d, J = 23.9 Hz, 1H), 2.02 (s, 1H), 0.93 (s, 1H), 0.84 - 0.74 (m, 6H)
MS(ESI+) m/z 479, 481 (M+H)+
실시예 335: N-(4-(1-(6- 클로로니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(6-chloronicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00435
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.55 (s, 1H), 8.59 - 8.51 (m, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.83 (s, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.32 (s, 1H), 6.50 (d, J = 13.3 Hz, 1H), 6.08 (d, J = 69.0 Hz, 1H), 4.57 - 4.17 (m, 1H), 4.14 (s, 1H), 3.65 (d, J = 12.5 Hz, 1H), 3.02 (s, 1H), 2.02 (dq, J = 8.1, 3.9, 2.8 Hz, 1H), 0.93 (s, 1H), 0.85 - 0.75 (m, 6H)
MS(ESI+) m/z 436, 438 (M+H)+
실시예 336: N-(4-(1- 이소니코티노일 -3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-isonicotinoyl-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00436
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.74 - 8.64 (m, 2H), 7.83 (d, J = 10.7 Hz, 1H), 7.48 - 7.44 (m, 2H), 7.32 (dt, J = 10.4, 2.9 Hz, 1H), 6.56 - 6.44 (m, 1H), 6.22 - 5.96 (m, 1H), 4.35 (dd, J = 166.5, 19.8 Hz, 1H), 4.06 (d, J = 9.2 Hz, 1H), 3.60 (dd, J = 13.4, 5.2 Hz, 1H), 3.02 (d, J = 39.5 Hz, 1H), 2.01 (td, J = 7.8, 7.4, 3.7 Hz, 1H), 0.94 (d, J = 6.8 Hz, 1H), 0.84 - 0.74 (m, 6H)
MS(ESI+) m/z 402 (M+H)+
실시예 337: N-(4-(1-(6- 브로모피콜리노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(6-bromopicolinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00437
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 7.94 - 7.89 (m, 1H), 7.85 (d, J = 6.6 Hz, 1H), 7.78 (dd, J = 8.1, 1.0 Hz, 1H), 7.69 (dd, J = 7.5, 3.8 Hz, 1H), 7.32 (dt, J = 10.3, 2.9 Hz, 1H), 6.49 (ddd, J = 8.0, 3.5, 1.9 Hz, 1H), 6.11 (dt, J = 60.3, 3.4 Hz, 1H), 4.61 - 4.17 (m, 1H), 4.16 - 4.11 (m, 1H), 3.63 (dd, J = 13.1, 3.5 Hz, 1H), 3.52 (dd, J = 13.3, 4.1 Hz, 1H), 3.04 (d, J = 32.1 Hz, 1H), 2.05 - 1.99 (m, 1H), 0.90 (dd, J = 35.3, 6.8 Hz, 3H), 0.83 - 0.72 (m, 4H)
MS(ESI+) m/z 480, 482 (M+H)+
실시예 338: N-(4-(1-(3- 브로모부타노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-bromobutanoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00438
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.55 (s, 1H), 7.83 (s, 1H), 7.32 (t, J = 2.9 Hz, 1H), 6.49 (s, 1H), 6.11 (s, 1H), 5.25 (s, 1H), 5.05 (s, 1H), 2.97 (s, 1H), 2.02 (s, 1H), 1.91 (s, 3H), 0.90 - 0.84 (m, 4H), 0.83 - 0.74 (m, 6H)
MS(ESI+) m/z 445, 447 (M+H)+
실시예 339: (E)-N-(4-(1-(5- 브로모펜트 -2- 에노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((E)-N-(4-(1-(5-bromopent-2-enoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00439
MS(ESI+) m/z 457, 459 (M+H)+
실시예 340: N-(4-(1-(2- 시클로펜틸아세틸 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyclopentylacetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00440
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.53 (s, 1H), 7.83 (d, J = 3.8 Hz, 1H), 7.32 (s, 1H), 6.48 (dd, J = 3.5, 1.8 Hz, 1H), 6.10 (d, J = 12.7 Hz, 1H), 4.36 (t, J = 17.9 Hz, 1H), 3.96 - 3.87 (m, 1H), 2.96 (d, J = 19.7 Hz, 1H), 2.02 (d, J = 5.6 Hz, 1H), 1.78 (d, J = 7.5 Hz, 2H), 1.59 (s, 2H), 1.50 (d, J = 7.3 Hz, 2H), 1.15 (s, 2H), 0.89 (d, J = 6.8 Hz, 2H), 0.84 - 0.77 (m, 7H)
MS(ESI+) m/z 407 (M+H)+
실시예 341: N-(4-(1-(2-(4- 메톡시페닐 )아세틸)-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-(4-methoxyphenyl)acetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00441
MS(ESI+) m/z 445 (M+H)+
실시예 342: N-(4-(3- 메틸 -1-(3- 메틸티오펜 -2-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(3-methylthiophene-2-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00442
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.59 (d, J = 5.0 Hz, 1H), 7.32 (d, J = 2.9 Hz, 1H), 6.96 (s, 1H), 6.47 (dd, J = 3.5, 1.8 Hz, 1H), 6.12 (s, 1H), 4.08 (d, J = 18.8 Hz, 2H), 2.01 (s, 1H), 0.86 (d, J = 6.9 Hz, 6H), 0.81 - 0.78 (m, 4H)
MS(ESI+) m/z 421 (M+H)+
실시예 343: N-(4-(3- 메틸 -1-( 피라진 -2-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(pyrazine-2-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00443
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.90 (dd, J = 6.0, 1.6 Hz, 1H), 8.77 (d, J = 2.5 Hz, 1H), 8.74 - 8.70 (m, 1H), 7.83 (d, J = 10.3 Hz, 1H), 7.32 (dt, J = 8.9, 3.0 Hz, 1H), 6.49 (ddd, J = 9.7, 3.5, 1.8 Hz, 1H), 6.21 - 5.96 (m, 1H), 4.31 - 4.11 (m, 2H), 2.01 (s, 1H), 0.95 (d, J = 6.8 Hz, 2H), 0.82 - 0.74 (m, 7H)
MS(ESI+) m/z 403 (M+H)+
실시예 344: N-(4-(3- 메틸 -1-(5- 메틸피라진 -2-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(5-methylpyrazine-2-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00444
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.76 (d, J = 7.1 Hz, 1H), 8.61 (s, 1H), 7.83 (d, J = 9.7 Hz, 1H), 7.36 - 7.29 (m, 1H), 6.48 (d, J = 9.3 Hz, 1H), 6.10 (d, J = 72.7 Hz, 1H), 4.23 - 4.10 (m, 2H), 2.01 (s, 1H), 1.23 (s, 3H), 0.81 - 0.77 (m, 7H)
MS(ESI+) m/z 417 (M+H)+
실시예 345: N-(4-(3- 메틸 -1-(2-(티오펜-2-일)아세틸)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(2-(thiophen-2-yl)acetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00445
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.53 (s, 1H), 7.82 (d, J = 7.2 Hz, 1H), 7.35 (dd, J = 26.6, 4.3 Hz, 3H), 7.00 - 6.93 (m, 3H), 6.45 (s, 1H), 6.09 (d, J = 15.0 Hz, 1H), 4.52 - 4.16 (m, 2H), 4.04 (dd, J = 17.1, 3.4 Hz, 2H), 2.95 (d, J = 8.0 Hz, 1H), 2.01 (s, 1H), 0.84 (d, J = 6.9 Hz, 3H), 0.81 - 0.77 (m, 4H)
MS(ESI+) m/z 421 (M+H)+
실시예 346: N-(4-(1-(2-(3- 플루오로페닐 )아세틸)-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-(3-fluorophenyl)acetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00446
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.53 (s, 1H), 7.82 (d, J = 5.9 Hz, 1H), 7.36 (dd, J = 6.4, 2.8 Hz, 1H), 7.33 - 7.31 (m, 1H), 7.13 (d, J = 9.0 Hz, 1H), 7.10 - 7.03 (m, 2H), 6.44 (p, J = 2.1 Hz, 1H), 6.09 (dd, J = 18.3, 3.5 Hz, 1H), 4.37 (dd, J = 28.8, 18.3 Hz, 1H), 4.12 (dd, J = 11.4, 6.1 Hz, 1H), 3.85 (d, J = 13.5 Hz, 2H), 3.71 (s, 2H), 2.04 - 1.98 (m, 1H), 0.83 (dd, J = 6.9, 2.0 Hz, 3H), 0.80 - 0.74 (m, 4H)
MS(ESI+) m/z 433 (M+H)+
실시예 347: N-(4-(1-(2-(3- 브로모페닐 )아세틸)-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(2-(3-bromophenyl)acetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00447
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.12 (d, J = 6.2 Hz, 1H), 7.83 (d, J = 6.5 Hz, 1H), 7.49 (d, J = 15.6 Hz, 1H), 7.44 (dt, J = 6.6, 3.1 Hz, 1H), 7.28 (s, 1H), 6.74 - 6.68 (m, 1H), 6.47 - 6.41 (m, 1H), 6.09 (dt, J = 15.0, 3.4 Hz, 1H), 4.08 (d, J = 50.7 Hz, 2H), 3.84 (d, J = 15.6 Hz, 2H), 3.71 (s, 2H), 2.96 (s, 1H), 2.01 (t, J = 4.9 Hz, 1H), 0.84 (d, J = 6.8 Hz, 3H), 0.81 - 0.76 (m, 4H)
MS(ESI+) m/z 494 (M+H)+
실시예 348: N-(4-(1-(2- 클로로아세틸 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(2-chloroacetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00448
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.32 (t, J = 3.0 Hz, 1H), 6.48 (d, J = 3.1 Hz, 1H), 6.10 (d, J = 13.3 Hz, 1H), 4.52 - 4.41 (m, 2H), 4.37 - 4.04 (m, 2H), 2.97 (s, 1H), 2.00 (q, J = 7.3, 6.1 Hz, 1H), 0.88 (dd, J = 17.0, 6.9 Hz, 3H), 0.79 (dd, J = 9.1, 6.0 Hz, 4H)
MS(ESI+) m/z 373, 375 (M+H)+
실시예 349: N-(4-(1-(2- 클로로니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(2-chloronicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00449
MS(ESI+) m/z 436, 438 (M+H)+
실시예 350: N-(4-(1-(4- 히드록시벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(4-hydroxybenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00450
MS(ESI+) m/z 417 (M+H)+
실시예 351: N-(4-(1-(3,5- 디클로로 -2- 히드록시벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(3,5-dichloro-2-hydroxybenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00451
MS(ESI+) m/z 486 (M+H)+
실시예 352: N-(4-(1-( 벤조퓨란 -2- 카보닐 )-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(benzofuran-2-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00452
MS(ESI+) m/z 441 (M+H)+
실시예 353: N-(4-(1-(3,4- 디클로로벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(3,4-dichlorobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00453
MS(ESI+) m/z 469, 471, 473 (M+H)+
실시예 354: N-(4-(3- 메틸 -1-(4-( 메틸술포닐 ) 벤조일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판 카복스아마이드 N-(4-(3-methyl-1-(4-(methylsulfonyl)benzoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00454
MS(ESI+) m/z 479 (M+H)+
실시예 355: N-(4-(1-(2- 클로로 -4- 플루오로벤조일 )-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(2-chloro-4-fluorobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00455
MS(ESI+) m/z 453, 455 (M+H)+
실시예 356: N-(4-(1-(2,4- 디메톡시벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(2,4-dimethoxybenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00456
MS(ESI+) m/z 461 (M+H)+
실시예 357: N-(4-(3- 메틸 -1-(2-( 메틸티오 ) 벤조일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(2-(methylthio)benzoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00457
MS(ESI+) m/z 447 (M+H)+
실시예 358: N-(4-(1-(3,5- 디플루오로벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 N-(4-(1-(3,5-difluorobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00458
MS(ESI+) m/z 437 (M+H)+
실시예 359: N-(4-(1-(2-시아노-3-(4-플루오로페닐)프로파노일)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyano-3-(4-fluorophenyl)propanoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00459
MS(ESI+) m/z 472 (M+H)+
실시예 360: N-(4-(1-(2- 시아노 -3- 페닐프로파노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyano-3-phenylpropanoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00460
MS(ESI+) m/z 454 (M+H)+
실시예 361: N-(4-(1-(1- 시아노사이클로펜탄 -1- 카보닐 )-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-cyanocyclopentane-1-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00461
MS(ESI+) m/z 418 (M+H)+
실시예 362: N-(4-(3- 메틸 -1-(3- 모르폴리노 -3- 옥소프로파노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(3-morpholino-3-oxopropanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00462
MS(ESI+) m/z 452 (M+H)+
실시예 363: N-(4-(1-(2- 시아노아세틸 )-2- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00463
MS(ESI+) m/z 364 (M+H)+
실시예 364: N-(4-(3- 메틸 -1-(1H-피롤-2-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(1H-pyrrole-2-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00464
MS(ESI+) m/z 390 (M+H)+
실시예 365: N-(4-(3- 메틸 -1-(2- 페닐아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(2-phenylacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00465
1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.53 (s, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.33 - 7.23 (m, 6H), 6.41 (d, J = 3.8 Hz, 1H), 6.07 (d, J = 23.4 Hz, 1H), 4.37 (dd, J = 29.9, 18.8 Hz, 1H), 4.13 - 4.01 (m, 1H), 3.81 (dd, J = 11.9, 4.6 Hz, 2H), 2.88 (s, 1H), 2.08 (d, J = 1.5 Hz, 2H), 2.01 (d, J = 1.5 Hz, 1H), 0.86 - 0.77 (m, 7H)
MS(ESI+) m/z 415 (M+H)+
실시예 366: N-(4-(9-(2- 플루오로이소니코티노일 )-9- 아자비시클로[3.3.1]논 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(9-(2-fluoroisonicotinoyl)-9-azabicyclo[3.3.1]non-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00466
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.55 (d, J = 3.3 Hz, 1H), 8.35 (t, J = 5.6 Hz, 1H), 7.90 (d, J = 3.2 Hz, 1H), 7.47 - 7.38 (m, 1H), 7.37 - 7.25 (m, 2H), 6.53 (ddd, J = 33.6, 3.5, 1.8 Hz, 1H), 6.30 (dd, J = 68.3, 5.4 Hz, 1H), 5.34 - 4.94 (m, 1H), 4.31 - 3.88 (m, 1H), 2.96 (dd, J = 17.4, 8.2 Hz, 1H), 2.37 (d, J = 17.9 Hz, 1H), 2.02 (s, 1H), 1.86 - 1.54 (m, 6H), 0.89 -0.71 (m, 4H)
MS(ESI+) m/z 446 (M+H)+
실시예 367: N-(4-(9-(2- 클로로이소니코티노일 )-9- 아자비시클로[3.3.1]논 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(9-(2-chloroisonicotinoyl)-9-azabicyclo[3.3.1]non-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00467
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.66 - 10.23 (m, 1H), 8.52 (dd, J = 7.0, 5.0 Hz, 1H), 7.90 (d, J = 3.4 Hz, 1H), 7.62 (d, J = 24.1 Hz, 1H), 7.54 - 7.42 (m, 1H), 7.35 (dt, J = 6.7, 2.9 Hz, 1H), 6.53 (ddd, J = 31.9, 3.6, 1.9 Hz, 1H), 6.31 (dd, J = 63.6, 5.4 Hz, 1H), 5.36 - 4.91 (m, 1H), 4.33 - 3.82 (m, 1H), 2.97 (dt, J = 17.0, 7.9 Hz, 1H), 2.37 (d, J = 18.0 Hz, 1H), 2.01 (d, J = 8.1 Hz, 1H), 1.89 - 1.55 (m, 6H), 0.86 - 0.72 (m, 4H)
MS(ESI+) m/z 462, 464 (M+H)+
실시예 368: N-(4-(9-(6- 클로로니코티노일 )-9- 아자비시클로[3.3.1]논 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(9-(6-chloronicotinoyl)-9-azabicyclo[3.3.1]non-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00468
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.55 (s, 1H), 8.53 (dd, J = 12.8, 2.3 Hz, 1H), 7.97 (ddd, J = 16.5, 8.3, 2.4 Hz, 1H), 7.90 (s, 1H), 7.62 (t, J = 8.2 Hz, 1H), 7.35 (dt, J = 8.3, 2.8 Hz, 1H), 6.61 - 6.47 (m, 1H), 6.31 (dd, J = 63.7, 5.4 Hz, 1H), 5.35 - 4.89 (m, 1H), 4.23 (d, J = 141.9 Hz, 1H), 2.99 (dd, J = 18.2, 7.2 Hz, 1H), 2.38 (d, J = 17.9 Hz, 1H), 2.08 - 1.97 (m, 1H), 1.87 - 1.57 (m, 6H), 0.85 - 0.71 (m, 4H)
MS(ESI+) m/z 462, 464 (M+H)+
실시예 369: N-(4-(9-(3- 플루오로이소니코티노일 )-9- 아자비시클로[3.3.1]논 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(9-(3-fluoroisonicotinoyl)-9-azabicyclo[3.3.1]non-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00469
1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.56 (s, 1H), 8.72 (d, J = 2.5 Hz, 1H), 8.54 (dt, J = 4.4, 2.1 Hz, 1H), 7.90 (d, J = 7.1 Hz, 1H), 7.58 (t, J = 5.3 Hz, 1H), 7.36 (dt, J = 8.5, 3.0 Hz, 1H), 6.51 (ddd, J = 30.4, 3.6, 1.9 Hz, 1H), 6.31 (dd, J = 71.8, 5.5 Hz, 1H), 5.20 (d, J = 113.1 Hz, 1H), 4.04 (d, J = 127.2 Hz, 1H), 2.92 (td, J = 21.1, 18.1, 6.8 Hz, 1H), 2.39 (d, J = 17.9 Hz, 1H), 2.02 (d, J = 7.6 Hz, 1H), 1.86 (d, J = 10.6 Hz, 2H), 1.74 (d, J = 34.5 Hz, 3H), 1.62 (d, J = 12.4 Hz, 1H), 0.86 - 0.72 (m, 4H)
MS(ESI+) m/z 446 (M+H)+
실시예 370: N-(4-(9-(4- 니트로벤조일 )-9- 아자비시클로[3.3.1]논 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(9-(4-nitrobenzoyl)-9-azabicyclo[3.3.1]non-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00470
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.31 (dd, J = 8.4, 5.7 Hz, 2H), 7.91 (d, J = 2.6 Hz, 1H), 7.73 (dd, J = 14.0, 8.4 Hz, 2H), 7.36 (dt, J = 10.5, 3.0 Hz, 1H), 6.61 - 6.47 (m, 1H), 6.31 (dd, J = 82.6, 5.4 Hz, 1H), 5.16 (d, J = 118.0 Hz, 1H), 4.13 (d, J = 138.3 Hz, 1H), 2.97 (ddd, J = 25.3, 18.1, 7.3 Hz, 1H), 2.38 (d, J = 17.9 Hz, 1H), 2.01 (d, J = 14.0 Hz, 1H), 1.81 (d, J = 30.8 Hz, 3H), 1.64 (d, J = 22.4 Hz, 3H), 0.83 - 0.74 (m, 4H)
MS(ESI+) m/z 472 (M+H)+
실시예 371: N-(4-(9-(3- 브로모벤조일 )-9- 아자비시클로[3.3.1]논 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(9-(3-bromobenzoyl)-9-azabicyclo[3.3.1]non-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00471
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.55 (s, 1H), 7.90 (s, 1H), 7.68 (d, J = 7.1 Hz, 1H), 7.63 (d, J = 15.3 Hz, 1H), 7.50 - 7.39 (m, 2H), 7.36 (dd, J = 7.1, 3.9 Hz, 1H), 6.59 - 6.46 (m, 1H), 6.32 (dd, J = 60.3, 5.3 Hz, 1H), 5.12 (d, J = 114.0 Hz, 1H), 4.20 (d, J = 137.6 Hz, 1H), 3.03 - 2.84 (m, 1H), 2.45 - 2.33 (m, 1H), 2.02 (s, 1H), 1.83 (s, 3H), 1.71 (d, J = 24.0 Hz, 2H), 1.61 (d, J = 9.5 Hz, 1H), 0.85 - 0.73 (m, 4H)
MS(ESI+) m/z 506 (M+H)+
실시예 372: N-(4-(1-(2,6- 디클로로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,6-dichloroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00472
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (d, J = 13.7 Hz, 1H), 7.72 (d, J = 6.8 Hz, 2H), 7.36 - 7.29 (m, 1H), 6.49 (d, J = 9.7 Hz, 1H), 6.07 (d, J = 65.0 Hz, 1H), 4.50 (d, J = 19.2 Hz, 1H), 4.17 - 4.01 (m, 3H), 2.01 (s, 1H), 1.23 (s, 3H), 0.80 (d, J = 7.3 Hz, 4H)
MS(ESI+) m/z 471 (M+H)+
실시예 373: N-(4-(1-(2,5- 디클로로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,5-dichloroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00473
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.54 (s, 1H), 8.65 (s, 1H), 7.86 (d, J = 5.7 Hz, 1H), 7.81 - 7.75 (m, 1H), 7.35 - 7.28 (m, 1H), 6.48 (d, J = 19.5 Hz, 1H), 6.08 (d, J = 63.9 Hz, 1H), 4.62 - 4.09 (m, 1H), 3.92 (d, J = 32.5 Hz, 1H), 2.02 (d, J = 7.1 Hz, 1H), 0.97 (s, 2H), 0.83 - 0.74 (m, 7H)
MS(ESI+) m/z 471 (M+H)+
실시예 374: N-(4-(1-(3,5- 디클로로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3,5-dichloroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00474
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.78 (d, J = 4.8 Hz, 2H), 7.83 (d, J = 15.9 Hz, 1H), 7.33 (s, 1H), 6.46 (d, J = 11.8 Hz, 1H), 6.09 (d, J = 71.5 Hz, 1H), 4.30 - 4.19 (m, 1H), 2.01 (s, 2H), 0.99 (d, J = 6.9 Hz, 2H), 0.87 - 0.71 (m, 7H)
MS(ESI+) m/z 470, 472, 474 (M+H)+
실시예 375: N-(4-(1-(2- 클로로 -6- 메틸이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-chloro-6-methylisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00475
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (d, J = 12.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 10.1 Hz, 1H), 7.31 (t, J = 3.6 Hz, 1H), 6.50 (dd, J = 10.5, 2.8 Hz, 1H), 6.08 (d, J = 65.0 Hz, 1H), 4.32 (dd, J = 170.8, 19.5 Hz, 1H), 4.05 (s, 1H), 3.59 (d, J = 10.5 Hz, 1H), 2.96 (s, 1H), 2.03 - 1.97 (m, 1H), 0.94 (d, J = 6.8 Hz, 2H), 0.85 - 0.70 (m, 7H)
MS(ESI+) m/z 450, 452 (M+H)+
실시예 376: N-(4-(1-(3- 클로로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-chloroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00476
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.54 (s, 1H), 8.77 (s, 1H), 8.64 (d, J = 5.1 Hz, 1H), 7.83 (d, J = 16.8 Hz, 1H), 7.53 (d, J = 4.7 Hz, 1H), 7.35 - 7.30 (m, 1H), 6.47 (d, J = 13.2 Hz, 1H), 6.09 (d, J = 68.6 Hz, 1H), 4.37 (d, J = 21.7 Hz, 1H), 3.91 (s, 1H), 2.01 (s, 1H), 0.98 (s, 2H), 0.88 - 0.74 (m, 7H)
MS(ESI+) m/z 436, 438 (M+H)+
실시예 377: N-(4-(1-(3- 히드록시이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-hydroxyisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00477
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (d, J = 5.8 Hz, 1H), 8.26 (s, 1H), 8.11 (d, J = 4.8 Hz, 1H), 7.80 (s, 1H), 7.21 (t, J = 3.6 Hz, 1H), 6.48 (s, 1H), 6.03 (d, J = 21.4 Hz, 1H), 5.81 (d, J = 7.7 Hz, 1H), 4.53 (d, J = 19.6 Hz, 1H), 3.93 (s, 1H), 2.96 (s, 2H), 2.01 (s, 1H), 1.00 - 0.90 (m, 3H), 0.76 (d, J = 6.4 Hz, 4H)
MS(ESI+) m/z 418 (M+H)+
실시예 378: N-(4-(1-(2,3- 디플루오로벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,3-difluorobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00478
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.20 - 8.09 (m, 1H), 7.83 (d, J = 14.1 Hz, 1H), 7.52 (d, J = 4.4 Hz, 1H), 7.33 (q, J = 5.2, 4.0 Hz, 1H), 6.48 (d, J = 8.4 Hz, 1H), 6.07 (d, J = 75.5 Hz, 1H), 4.63 - 4.19 (m, 1H), 4.15 (s, 1H), 4.04 (d, J = 7.8 Hz, 1H), 2.93 (s, 1H), 2.01 (s, 1H), 0.95 - 0.77 (m, 7H)
MS(ESI+) m/z 437 (M+H)+
실시예 379: N-(4-(3- 메틸 -1-(2- 메틸이소니코티노일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-methyl-1-(2-methylisonicotinoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00479
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 7.83 (d, J = 10.1 Hz, 1H), 7.31 (d, J = 8.6 Hz, 2H), 7.24 (s, 1H), 6.49 (d, J = 14.8 Hz, 1H), 6.08 (d, J = 70.1 Hz, 1H), 4.33 (dd, J = 173.7, 19.7 Hz, 1H), 4.04 (s, 1H), 2.52 (s, 3H), 2.01 (s, 1H), 0.94 - 0.77 (m, 7H)
MS(ESI+) m/z 416 (M+H)+
실시예 380: N-(4-(1-(6- 메톡시니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(6-methoxynicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00480
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.32 - 8.24 (m, 1H), 7.82 (d, J = 11.3 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 7.03 (d, J = 5.2 Hz, 1H), 6.86 (s, 1H), 6.49 (d, J = 13.4 Hz, 1H), 6.08 (d, J = 67.4 Hz, 1H), 4.58 - 4.08 (m, 1H), 4.04 (s, 1H), 3.89 (s, 3H), 3.59 (d, J = 13.6 Hz, 2H), 2.95 (s, 1H), 2.01 (s, 1H), 0.94 - 0.77 (m, 7H)
MS(ESI+) m/z 432 (M+H)+
실시예 381: N-(4-(1-(2- 아미노이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-aminoisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00481
MS(ESI+) m/z 417 (M+H)+
실시예 382: N-(4-(1-(2- 브로모이소니오노티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-bromoisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00482
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 7.83 (d, J = 12.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.59 - 7.48 (m, 1H), 7.33 (dd, J = 7.4, 4.4 Hz, 1H), 6.55 - 6.41 (m, 1H), 6.08 (d, J = 65.3 Hz, 1H), 4.33 (dd, J = 166.6, 19.5 Hz, 1H), 4.05 (d, J = 3.5 Hz, 1H), 3.59 (dd, J = 13.2, 4.2 Hz, 1H), 3.02 (d, J = 40.4 Hz, 1H), 2.00 (dt, J = 7.9, 4.7 Hz, 1H), 0.95 - 0.77 (m, 7H)
MS(ESI+) m/z 481 (M+H)+
실시예 383: N-(4-(1-(2- 히드록시이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-hydroxyisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00483
MS(ESI+) m/z 418 (M+H)+
실시예 384: N-(4-(3- 메틸 -1-(2-( 트리플루오로메틸 ) 이소니코티노일 )-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]사이클로프로판 카르복사미드 (N-(4-(3-methyl-1-(2-(trifluoromethyl)isonicotinoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00484
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.90 (d, J = 4.9 Hz, 1H), 8.03 - 7.77 (m, 3H), 7.37 - 7.26 (m, 1H), 6.50 (d, J = 12.5 Hz, 1H), 6.08 (d, J = 73.2 Hz, 1H), 4.62 - 4.13 (m, 1H), 4.07 (s, 1H), 2.98 (s, 1H), 2.07 - 1.96 (m, 1H), 0.97 - 0.77 (m, 7H)
MS(ESI+) m/z 470 (M+H)+
실시예 385: N-(4-(1-(2- 플루오로이소니코티노일 )-2,2-디메틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-fluoroisonicotinoyl)-2,2-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00485
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.34 (d, J = 5.1 Hz, 1H), 7.90 (s, 1H), 7.43 - 7.33 (m, 2H), 7.27 (d, J = 2.2 Hz, 1H), 6.54 (dd, J = 3.6, 1.9 Hz, 1H), 6.45 (t, J = 4.6 Hz, 1H), 3.95 (d, J = 4.5 Hz, 2H), 2.72 (s, 2H), 2.03 (hept, J = 4.7 Hz, 1H), 1.58 (s, 6H), 0.87 - 0.71 (m, 4H).
MS(ESI+) m/z 434 (M+H)+
실시예 386: N-(4-(1-(2- 클로로이소니코티노일 )-2,2-디메틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-chloroisonicotinoyl)-2,2-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00486
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.57 - 8.44 (m, 1H), 7.90 (s, 1H), 7.59 (s, 1H), 7.45 (s, 1H), 7.35 (s, 1H), 6.49 (d, J = 35.6 Hz, 2H), 3.95 (s, 2H), 2.72 (s, 2H), 2.03 (s, 1H), 1.57 (d, J = 5.9 Hz, 6H), 0.83 (d, J = 20.3 Hz, 4H)
MS(ESI+) m/z 450, 452 (M+H)+
실시예 387: N-(4-(1-(2- 시아노아세틸 )-2,2-디메틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2,2-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00487
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.56 (s, 1H), 7.89 (s, 1H), 7.36 (t, J = 3.0 Hz, 1H), 6.54 (dd, J = 3.5, 1.8 Hz, 1H), 6.46 (t, J = 4.6 Hz, 1H), 4.09 (s, 2H), 4.02 (d, J = 4.6 Hz, 2H), 2.64 (s, 2H), 2.05 - 1.98 (m, 1H), 1.47 (s, 6H), 0.85 - 0.71 (m, 4H)
MS(ESI+) m/z 378 (M+H)+
실시예 388: (R)-N-(4-(1-(2- 시아노아세틸 )-6- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((R)-N-(4-(1-(2-cyanoacetyl)-6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00488
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.53 (s, 1H), 7.85 (d, J = 3.4 Hz, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.60 - 6.38 (m, 1H), 6.24 (dd, J = 24.2, 3.9 Hz, 1H), 4.99 - 4.41 (m, 1H), 4.59 - 3.69 (ddd, J = 13.8, 5.2 Hz, 1H), 4.14 (m, 1H), 3.04 - 2.75 (m, 1H), 2.46 - 2.31 (m, 1H), 2.08 - 1.93 (m, 1H), 1.31 (dd, J = 42.5, 6.8 Hz, 3H), 0.80 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 389: (R)-N-(4-(1-(2- 시아노아세틸 )-2- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((R)-N-(4-(1-(2-cyanoacetyl)-2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00489
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.54 (s, 1H), 7.85 (s, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.53 (d, J = 3.0 Hz, 1H), 6.28 (d, J = 23.9 Hz, 1H), 5.02 - 4.88 (m, 1H), 4.66 (d, J = 20.0 Hz, 1H), 4.28 - 3.95 (m, 4H), 3.66 (d, J = 20.5 Hz, 1H), 3.01 (d, J = 17.1 Hz, 1H), 2.37 - 2.26 (m, 1H), 2.08 - 1.93 (m, 1H), 1.31-1.18 (m, 3H), 0.82 (m, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 390: (S)-N-(4-(1-(2- 시아노아세틸 )-6- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-cyanoacetyl)-6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00490
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.53 (s, 1H), 7.85 (d, J = 3.7 Hz, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.53 (dd, J = 3.4, 1.7 Hz, 1H), 6.33 - 6.13 (m, 1H), 4.99 -4.40 (m, 1H), 4.56 - 3.71 (dd, J = 13.7, 5.2 Hz, 1H), 4.34 - 3.97 (m, 2H), 3.39 - 3.23 (m, 1H), 2.87 (dt, J = 46.3, 13.5 Hz, 1H), 2.48 - 2.31 (m, 1H), 2.1 - 1.95 (m, 1H), 1.31 (dd, J = 42.6, 6.7 Hz, 3H)., 0.80 (dt, J = 11.5, 5.5 Hz, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 391: (S)-N-(4-(1-(2- 시아노아세틸 )-2- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-cyanoacetyl)-2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00491
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.54 (s, 1H), 7.85 (s, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.53 (d, J = 3.0 Hz, 1H), 6.28 (d, J = 23.9 Hz, 1H), 5.02 - 4.88 (m, 1H), 4.66 (d, J = 20.0 Hz, 1H), 4.28 - 3.95 (m, 4H), 3.66 (d, J = 20.5 Hz, 1H), 3.01 (d, J = 17.1 Hz, 1H), 2.37 - 2.26 (m, 1H), 2.08 - 1.93 (m, 1H), 1.31-1.18 (m, 3H), 0.82 (m, 4H).
MS(ESI+) m/z 364 (M+H)+
실시예 392: N-(4-(1-(2- 시아노이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00492
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.59 (d, J = 3.2 Hz, 1H), 8.87 (d, J = 5.4 Hz, 1H), 8.20 (d, J = 9.9 Hz, 1H), 7.83 (q, J = 4.9 Hz, 2H), 7.33 (d, J = 9.6 Hz, 1H), 6.50 (d, J = 15.1 Hz, 1H), 6.07 (d, J = 75.8 Hz, 1H), 4.59 - 4.15 (m, 1H), 4.06 (s, 1H), 3.58 (s, 1H), 3.26 (s, 1H), 3.03 (d, J = 43.5 Hz, 1H), 2.00 (s, 1H), 0.95 - 0.76 (m, 7H).
MS(ESI+) m/z 427 (M+H)+
실시예 393: N-(4-(1-(2- 시아노아세틸 )-2-( 트리플루오로메틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2-(trifluoromethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00493
MS(ESI+) m/z 418 (M+H)+
실시예 394: N-(4-(9-(2- 시아노아세틸 )-9- 아자비시클로[3.3.1]논 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(9-(2-cyanoacetyl)-9-azabicyclo[3.3.1]non-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00494
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.55 (s, 1H), 7.89 (s, 1H), 7.35 (d, J = 3.2 Hz, 1H), 6.55 (d, J = 11.5 Hz, 1H), 6.29 (d, J = 13.7 Hz, 1H), 5.17 (s, 1H), 4.71 (d, J = 141.5 Hz, 1H), 4.22 - 4.11 (m, 2H), 3.18 - 3.07 (m, 1H), 2.91 - 2.64 (m, 1H), 2.38 (d, J = 18.0 Hz, 2H), 2.02 (s, 1H), 1.80 (d, J = 8.8 Hz, 2H), 1.62 (d, J = 31.9 Hz, 2H), 0.79 (d, J = 11.9 Hz, 4H).
MS(ESI+) m/z 390 (M+H)+
실시예 395: (S)-N-(4-(1-(2- 플루오로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-fluoroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00495
MS(ESI+) m/z 420 (M+H)+
실시예 396: (S)-N-(4-(1-(2,3- 디플루오로이소니코티노일 )-3- 메틸 -1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2,3-difluoroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00496
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.55 (s, 1H), 8.21 - 8.13 (m, 1H), 7.84 (d, J = 14.3 Hz, 1H), 7.58 - 7.49 (m, 1H), 7.33 (dt, J = 5.5, 2.8 Hz, 1H), 6.48 (d, J = 8.5 Hz, 1H), 6.08 (dd, J = 75.5, 3.0 Hz, 1H), 4.63 - 4.22 (m, 1H), 4.18 (d, J = 18.5 Hz, 1H), 4.12 - 3.92 (m, 1H), 3.61 (dd, J = 30.9, 12.6 Hz, 1H), 3.01 (d, J = 64.9 Hz, 1H), 2.02 (s, 1H), 0.97 - 0.91 (m, 1H), 0.84 - 0.73 (m, 6H).
MS(ESI+) m/z 438 (M+H)+
실시예 397: (S)-N-(4-(1-(3- 브로모벤조일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(3-bromobenzoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00497
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.83 (s, 1H), 7.67 (t, J = 8.0 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.32 (s, 1H), 6.50 (s, 1H), 6.21 - 5.96 (m, 1H), 4.59 - 4.12 (m, 1H), 4.09 (s, 1H), 3.61 (d, J = 12.3 Hz, 1H), 3.02 (d, J = 28.7 Hz, 1H), 2.01 (d, J = 7.7 Hz, 1H), 0.94 - 0.75 (m, 7H).
MS(ESI+) m/z 479, 481 (M+H)+
실시예 398: (S)-N-(4-(3- 메틸 -1-(4- 니트로벤조일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(3-methyl-1-(4-nitrobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00498
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.33 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 9.4 Hz, 1H), 7.75 (d, J = 8.1 Hz, 2H), 7.33 (s, 1H), 6.50 (d, J = 17.6 Hz, 1H), 6.09 (d, J = 79.5 Hz, 1H), 4.37 (dd, J = 155.9, 19.7 Hz, 1H), 4.08 (d, J = 23.1 Hz, 1H), 3.61 (d, J = 13.3 Hz, 1H), 3.13 - 2.93 (m, 1H), 2.02 (s, 1H), 0.98 - 0.90 (m, 1H), 0.79 (t, J = 8.0 Hz, 6H).
MS(ESI+) m/z 446 (M+H)+
실시예 399: (S)-N-(4-(1-(2- 클로로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-chloroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00499
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.61 - 8.46 (m, 1H), 7.84 (d, J = 12.1 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.50 (d, J = 5.6 Hz, 1H), 7.38 - 7.26 (m, 1H), 6.53 - 6.42 (m, 1H), 6.23 - 5.97 (m, 1H), 4.34 (dd, J = 164.5, 20.3 Hz, 1H), 4.05 (s, 1H), 3.63 - 3.53 (m, 1H), 3.12 - 2.93 (m, 1H), 2.01 (d, J = 7.4 Hz, 1H), 0.94 (d, J = 6.8 Hz, 1H), 0.84 - 0.74 (m, 6H).
MS(ESI+) m/z 436, 438 (M+H)+
실시예 400: (S)-N-(4-(1-(6- 클로로니코티노일 )-3- 메틸 -1,2,3,6- 테트라하이드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(6-chloronicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00500
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.55 (s, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.84 (s, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 5.2 Hz, 1H), 6.50 (d, J = 13.3 Hz, 1H), 6.09 (d, J = 69.3 Hz, 1H), 4.57 - 4.18 (m, 1H), 4.14 (s, 1H), 3.65 (d, J = 12.1 Hz, 1H), 3.05 (d, J = 23.3 Hz, 1H), 2.01 (d, J = 7.4 Hz, 1H), 0.94 (s, 1H), 0.83 - 0.74 (m, 6H).
MS(ESI+) m/z 436, 438 (M+H)+
실시예 401: (S)-N-(4-(1-(2- 클로로아세틸 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-chloroacetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00501
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 7.84 (d, J = 6.9 Hz, 1H), 7.33 (s, 1H), 6.48 (s, 1H), 6.10 (d, J = 14.2 Hz, 1H), 4.54 - 4.40 (m, 2H), 4.37 - 3.97 (m, 2H), 3.77 - 3.36 (m, 2H), 3.02 (d, J = 32.0 Hz, 1H), 2.01 (d, J = 7.2 Hz, 1H), 0.92 - 0.84 (m, 3H), 0.83 - 0.69 (m, 4H).
MS(ESI+) m/z 373, 375 (M+H)+
실시예 402: (S)-N-(4-(1-(3- 플루오로이소니코티노일 )-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(3-fluoroisonicotinoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00502
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.74 (s, 1H), 8.64 - 8.50 (m, 1H), 7.84 (d, J = 14.3 Hz, 1H), 7.58 (d, J = 4.9 Hz, 1H), 7.33 (dd, J = 7.1, 3.4 Hz, 1H), 6.49 (d, J = 10.2 Hz, 1H), 6.09 (d, J = 71.2 Hz, 1H), 4.70 - 4.08 (m, 2H), 3.99 (s, 1H), 3.59 (t, J = 14.5 Hz, 1H), 3.12 - 2.90 (m, 1H), 2.02 (s, 1H), 0.95 (d, J = 6.9 Hz, 1H), 0.79 (q, J = 6.6 Hz, 6H).
MS(ESI+) m/z 420 (M+H)+
실시예 403: (S)-N-(4-(1-(2- 시아노 -3-(티오펜-2-일)아크릴로일)-3- 메틸 -1,2,3,6-테트라히드로피리딘-4-일)-2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-cyano-3-(thiophen-2-yl)acryloyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00503
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 8.20 - 8.03 (m, 1H), 7.95 (s, 1H), 7.86 (q, J = 3.1 Hz, 1H), 7.57 (d, J = 6.6 Hz, 1H), 7.37 - 7.27 (m, 2H), 6.50 (s, 1H), 6.15 (d, J = 13.1 Hz, 1H), 4.45 (d, J = 18.5 Hz, 1H), 4.39 - 3.46 (m, 3H), 3.10 (s, 1H), 2.09 - 1.97 (m, 1H), 0.96 - 0.87 (m, 3H), 0.83 - 0.74 (m, 4H).
MS(ESI+) m/z 458 (M+H)+
실시예 404: (S)-N-(4-(1-(2-(시아노메틸)-3-페닐아크릴로일)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (S)-N-(4-(1-(2-(cyanomethyl)-3-phenylacryloyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00504
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.56 (s, 1H), 7.99 - 7.91 (m, 2H), 7.87 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 4.2 Hz, 2H), 7.50 (s, 1H), 7.34 (s, 1H), 6.51 (s, 1H), 6.13 (s, 1H), 4.47 (s, 1H), 4.37 - 4.07 (m, 1H), 3.97 (d, J = 22.1 Hz, 1H), 3.80 - 3.45 (m, 1H), 3.10 (s, 1H), 2.01 (d, J = 8.0 Hz, 1H), 0.92 (d, J = 7.1 Hz, 3H), 0.79 (t, J = 8.3 Hz, 4H).
MS(ESI+) m/z 466 (M+H)+
실시예 405: (S)-N-(4-(3-메틸-1-(1-메틸-2-옥소-1,2-디히드로피리딘-3-카르보닐)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(3-methyl-1-(1-methyl-2-oxo-1,2-dihydropyridine-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00505
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.54 (s, 1H), 7.82 (d, J = 12.8 Hz, 2H), 7.51 (d, J = 6.6 Hz, 1H), 7.32 (d, J = 6.5 Hz, 1H), 6.48 (s, 1H), 6.29 (d, J = 7.0 Hz, 1H), 6.08 (d, J = 54.1 Hz, 1H), 4.27 (dd, J = 137.1, 19.1 Hz, 2H), 4.00 (s, 1H), 3.56 (s, 1H), 3.49 (s, 3H), 2.98 (s, 1H), 2.02 (s, 1H), 0.94 (d, J = 6.9 Hz, 1H), 0.85 - 0.72 (m, 6H).
MS(ESI+) m/z 432 (M+H)+
실시예 406: (S)-N-(4-(1-(2-(1-시아노사이클로헥실)아세틸)-3-메틸-1,2,3,6-테트라하이드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-(1-cyanocyclohexyl)acetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00506
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.84 (d, J = 7.1 Hz, 1H), 7.33 (s, 1H), 6.49 (s, 1H), 6.09 (d, J = 20.9 Hz, 1H), 4.43 - 4.27 (m, 1H), 4.13 - 3.93 (m, 1H), 3.72 - 3.51 (m, 1H), 3.38 (d, J = 12.6 Hz, 1H), 2.99 (d, J = 23.7 Hz, 1H), 2.84 (d, J = 9.4 Hz, 1H), 2.69 (d, J = 8.1 Hz, 1H), 2.09 (d, J = 13.0 Hz, 2H), 2.01 (d, J = 7.2 Hz, 1H), 1.67 (d, J = 11.6 Hz, 3H), 1.54 - 1.33 (m, 4H), 1.18 (dd, J = 20.2, 9.7 Hz, 1H), 0.87 (dd, J = 17.1, 6.8 Hz, 3H), 0.83 - 0.71 (m, 4H).
MS(ESI+) m/z 446 (M+H)+
실시예 407: (S)-N-(4-(1-(4-시아노테트라하이드로-2H-피란-4-카보닐)-3-메틸-1,2,3,6-테트라하이드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(4-cyanotetrahydro-2H-pyran-4-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00507
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.84 (d, J = 6.7 Hz, 1H), 7.32 (t, J = 3.0 Hz, 1H), 6.48 (dt, J = 4.7, 2.3 Hz, 1H), 6.09 (dt, J = 28.1, 3.4 Hz, 1H), 4.28 (dd, J = 52.8, 18.4 Hz, 1H), 4.07 - 3.96 (m, 1H), 3.94 - 3.57 (m, 1H), 3.43 (ddd, J = 12.4, 7.9, 4.5 Hz, 1H), 3.00 (s, 1H), 2.90 - 2.62 (m, 2H), 2.01 (td, J = 7.4, 3.7 Hz, 1H), 1.34 - 1.14 (m, 3H), 1.01 - 0.89 (m, 2H), 0.87 (dd, J = 6.9, 5.1 Hz, 3H), 0.84 - 0.73 (m, 4H).
MS(ESI+) m/z 434 (M+H)+
실시예 408: (S)-N-(4-(1-(2-시아노-3-메틸뷰트-2-에노일)-3-메틸-1,2,3,6-테트라하이드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-cyano-3-methylbut-2-enoyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00508
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.56 (s, 1H), 7.84 (s, 1H), 7.33 (s, 1H), 6.48 (s, 1H), 6.11 (d, J = 21.5 Hz, 1H), 4.58 - 4.23 (m, 1H), 4.07 (t, J = 22.3 Hz, 2H), 3.77 - 3.55 (m, 1H), 3.54 - 3.44 (m, 1H), 3.03 (s, 1H), 2.14 (s, 3H), 2.02 (s, 1H), 1.93 (d, J = 7.1 Hz, 3H), 0.88 (d, J = 6.7 Hz, 3H), 0.79 (dd, J = 13.1, 5.2 Hz, 4H).
MS(ESI+) m/z 404 (M+H)+
실시예 409: N-(4-(1-(2- 시아노아세틸 )-2,6- 디에틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2,6-diethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00509
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.55 (s, 1H), 7.85 (s, 1H), 7.44 - 7.34 (m, 1H), 6.46 (dd, J = 3.8, 1.8 Hz, 1H), 6.30 (t, J = 3.0 Hz, 1H), 4.70 - 4.55 (m, 1H), 4.29 - 4.01 (m, 2H), 3.90 (d, J = 6.7 Hz, 1H), 2.01 (d, J = 5.2 Hz, 1H), 1.65 (dddd, J = 51.1, 21.4, 14.7, 7.4 Hz, 4H), 1.23 (s, 2H), 1.08 - 0.97 (m, 3H), 0.88 (dt, J = 13.5, 7.3 Hz, 3H), 0.83 - 0.71 (m, 4H).
MS(ESI+) m/z 406 (M+H)+
실시예 410: N-(4-(1-(2- 시아노아세틸 )-2-이소프로필-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2-isopropyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00510
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.54 (s, 1H), 7.87 (s, 1H), 7.35 (s, 1H), 6.58 - 6.40 (m, 1H), 6.37 - 6.19 (m, 1H), 4.29 - 4.08 (m, 2H), 4.08 - 3.89 (m, 1H), 3.84 - 3.54 (m, 1H), 3.01 - 2.81 (m, 1H), 2.37 (s, 1H), 2.01 (s, 2H), 1.23 (s, 2H), 1.06 (d, J = 6.6 Hz, 2H), 0.92 (t, J = 5.7 Hz, 2H), 0.87 (dd, J = 13.0, 6.5 Hz, 2H), 0.83 - 0.75 (m, 4H).
MS(ESI+) m/z 392 (M+H)+
실시예 411: N-(4-(1-(2- 시아노아세틸 )-6-프로필-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-6-propyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00511
MS(ESI+) m/z 392 (M+H)+
실시예 412: N-(4-(6-( tert -부틸)-1-(2- 시아노아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(6-(tert-butyl)-1-(2-cyanoacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00512
MS(ESI+) m/z 406 (M+H)+
실시예 413: N-(4-(1-(2- 시아노아세틸 )-2-에틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00513
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.54 (s, 1H), 7.85 (s, 1H), 7.35 (t, J = 2.9 Hz, 1H), 6.52 (s, 1H), 6.25 (d, J = 28.2 Hz, 1H), 4.81 - 4.65 (m, 1H), 4.20 - 4.08 (m, 2H), 4.00 - 3.90 (m, 1H), 3.01 (d, J = 17.1 Hz, 1H), 2.08 - 1.91 (m, 1H), 1.74 - 1.46 (m, 2H), 1.23 (s, 2H), 0.86 (dd, J = 12.2, 7.3 Hz, 3H), 0.86-0.69 (m, 4H).
MS(ESI+) m/z 378 (M+H)+
실시예 414: N-(4-(5-(2- 시아노아세틸 )-5- 아자스피로[3.5]논 -7-엔-8-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(5-(2-cyanoacetyl)-5-azaspiro[3.5]non-7-en-8-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00514
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.54 (s, 1H), 7.86 (s, 1H), 7.37 - 7.15 (m, 1H), 6.55 (s, 1H), 6.28 (s, 1H), 4.03 (s, 4H), 2.36 (s, 2H), 2.12 - 1.97 (m, 3H), 1.79 (dt, J = 28.8, 10.1 Hz, 2H), 0.83 - 0.74 (m, 4H).
MS(ESI+) m/z 390 (M+H)+
실시예 415: (S)-N-(4-(1-(2-(1-시아노시클로프로필)아세틸)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(2-(1-cyanocyclopropyl)acetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00515
MS(ESI+) m/z 404 (M+H)+
실시예 416: (R)-N-(4-(1-(2- 시아노아세틸 )-6-에틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((R)-N-(4-(1-(2-cyanoacetyl)-6-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00516
MS(ESI+) m/z 378 (M+H)+
실시예 417: (R)-N-(4-(1-(2- 시아노아세틸 )-2-에틸-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((R)-N-(4-(1-(2-cyanoacetyl)-2-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00517
MS(ESI+) m/z 378 (M+H)+
실시예 418: N-(4-(1-(3- 시아노프로파노일 )-1,4,5,6- 테트라히드로피리딘 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-cyanopropanoyl)-1,4,5,6-tetrahydropyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00518
MS(ESI+) m/z 364 (M+H)+
실시예 419: N-(4-(1-(2- 시아노아세틸 )-1,4,5,6- 테트라히드로피리딘 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-1,4,5,6-tetrahydropyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00519
MS(ESI+) m/z 350 (M+H)+
실시예 420: N-(4-(1-(2- 시아노아세틸 )-1,2,5,6- 테트라히드로피리딘 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-1,2,5,6-tetrahydropyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00520
1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.55 (d, J = 5.3 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.36 (q, J = 2.7 Hz, 1H), 6.60 - 6.50 (m, 1H), 6.48 - 6.33 (m, 1H), 4.35 (dd, J = 40.1, 2.7 Hz, 2H), 4.15 (d, J = 5.6 Hz, 2H), 3.61 (dt, J = 43.3, 5.8 Hz, 2H), 2.46 - 2.28 (m, 2H), 2.02 (d, J = 6.0 Hz, 1H), 0.90-0.71 (m, 4H).
MS(ESI+) m/z 350 (M+H)+
실시예 421: N-(4-(1-(3- 시아노프로파노일 )-1,2,5,6- 테트라히드로피리딘 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-cyanopropanoyl)-1,2,5,6-tetrahydropyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00521
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.55 (s, 1H), 7.86 (d, J = 4.1 Hz, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.58 - 6.51 (m, 1H), 6.48 - 6.39 (m, 1H), 4.46 - 4.29 (m, 2H), 3.65 (dt, J = 24.4, 5.8 Hz, 2H), 2.82 (dt, J = 14.1, 6.8 Hz, 2H), 2.64 (dt, J = 14.0, 6.7 Hz, 2H), 2.38 (d, J = 39.9 Hz, 2H), 2.01 (d, J = 7.9 Hz, 1H), 0.85 - 0.76 (m, 4H).
MS(ESI+) m/z 364 (M+H)+
실시예 422: N-(4-(1-(2- 시아노아세틸 )-2,5,6,7- 테트라하이드로 -1H- 아제핀 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00522
1H NMR (400 MHz, DMSO-d6) δ 11.40 (d, J = 7.3 Hz, 1H), 10.57 - 10.47 (m, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.32 (q, J = 3.0 Hz, 1H), 6.40 (ddd, J = 1.9, 3.6, 8.7 Hz, 1H), 6.24 (dt, J = 5.4, 32.4 Hz, 1H), 4.15 (dd, J = 5.4, 11.3 Hz, 2H), 4.08 (d, J = 20.8 Hz, 2H), 3.67 (dt, J = 5.9, 41.9 Hz, 2H), 2.71 (dt, J = 5.7, 16.7 Hz, 2H), 2.01 (t, J = 5.9 Hz, 1H), 1.96 (s, 1H), 1.91 (d, J = 12.1 Hz, 1H), 0.84-0.75 (m, 4H).
MS(ESI+) m/z 364 (M+H)+
실시예 423: N-(4-(1-(2- 플루오로이소니코티노일 )-2,5,6,7- 테트라하이드로 -1H-아제핀-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-fluoroisonicotinoyl)-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00523
MS(ESI+) m/z 420 (M+H)+
실시예 424: N-(4-(1-(2,3- 디플루오로이소니코티노일 )-2,5,6,7- 테트라하이드로 -1H-아제핀-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2,3-difluoroisonicotinoyl)-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00524
MS(ESI+) m/z 438 (M+H)+
실시예 425: N-(4-(1-(2- 시아노아세틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00525
1H NMR (400 MHz, DMSO-d6) δ 11.95 (s, 1H), 10.44 (d, J = 5.0 Hz, 1H), 7.42 (s, 1H), 6.89 (d, J = 11.4 Hz, 1H), 6.70 (s, 1H), 4.24 (d, J = 16.4 Hz, 2H), 4.14 (d, J = 17.7 Hz, 2H), 3.65 (dt, J = 5.8, 50.5 Hz, 2H), 2.85 - 2.62 (m, 2H), 2.17 (s, 1H), 0.81 - 0.77 (m, 4H).
MS(ESI+) m/z 351 (M+H)+
실시예 426: N-(4-(1-(2- 시아노아세틸 )-2,5- 디히드로 -1H-피롤-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoacetyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00526
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 10.61 (s, 1H), 7.85 (d, J = 3.2 Hz, 1H), 7.43 (s, 1H), 6.74 (d, J = 20.3 Hz, 2H), 4.75 (s, 1H), 4.55 (d, J = 16.5 Hz, 2H), 4.38 (s, 1H), 4.15 (d, J = 3.5 Hz, 1H), 4.04 (d, J = 3.2 Hz, 1H), 2.03 (s, 1H), 0.81 (s, 4H).
MS(ESI+) m/z 336 (M+H)+
실시예 427: N-(4-(1-(3- 시아노프로파노일 )-2,5- 디히드로 -1H-피롤-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-cyanopropanoyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00527
1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 10.60 (s, 1H), 7.86 (d, J = 5.1 Hz, 1H), 7.43 (d, J = 2.3 Hz, 1H), 6.79 - 6.69 (m, 2H), 4.77 (s, 1H), 4.56 (s, 2H), 4.40 - 4.31 (m, 1H), 2.96 (s, 1H), 2.83 (t, J = 6.9 Hz, 1H), 2.77 - 2.72 (m, 1H), 2.68 (q, J = 6.6 Hz, 2H), 2.02 (dd, J = 4.8, 9.6 Hz, 1H), 0.81 (dt, J = 4.0, 18.4 Hz, 4H).
MS(ESI+) m/z 350 (M+H)+
실시예 428: N-(4-(1-(3,3,3- 트리플루오로프로파노일 )-2,5- 디히드로 -1H-피롤-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3,3,3-trifluoropropanoyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00528
1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 10.60 (d, J = 2.7 Hz, 1H), 7.86 (d, J = 2.8 Hz, 1H), 7.43 (d, J = 3.1 Hz, 1H), 6.81 - 6.63 (m, 2H), 4.80 (d, J = 4.2 Hz, 1H), 4.58 (s, 2H), 4.38 (d, J = 4.0 Hz, 1H), 3.72 (dq, J = 11.0, 41.9 Hz, 2H), 2.02 (q, J = 3.0, 4.8 Hz, 1H), 0.87 - 0.74 (m, 4H).
MS(ESI+) m/z 379 (M+H)+
실시예 429: N-(4-(1-(4,4,4- 트리플루오로부타노일 )-2,5- 디히드로 -1H-피롤-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(4,4,4-trifluorobutanoyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00529
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.62 (s, 1H), 7.87 (s, 1H), 7.43 (s, 1H), 6.74 (t, J = 11.6 Hz, 2H), 4.80 (s, 1H), 4.57 (d, J = 10.9 Hz, 2H), 4.37 (s, 1H), 2.74 - 2.61 (m, 2H), 2.04 - 1.98 (m, 1H), 1.15 (s, 2H), 0.82 (dd, J = 6.5, 21.7 Hz, 4H).
MS(ESI+) m/z 393 (M+H)+
실시예 430: N-(4-(1-(1- 시아노시클로프로판 -1-카르보닐)-2,5- 디히드로 -1H-피롤-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-cyanocyclopropane-1-carbonyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00530
MS(ESI+) m/z 362 (M+H)+
실시예 431: N-(4-(4-(3- 에틸우레이도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(3- ethylureido ) phenyl )-1H- pyrrolo[2,3- b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00531
N-(4-(4-아미노페닐)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (100 mg)을 피리딘과 교반하였다. 혼합물에 아이소사이안화에틸 4 당량을 넣고, 실온에서 12시간 동안 교반하였다. 반응이 완료되면 상기 혼합물을 d-HCl을 첨가하고, 디클로로메탄으로 추출하여, 유기층을 분리하였다. 혼합물을 농축 후, MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 ~ 40 oC에서 4 시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온으로 냉각시키고, 교반하면서 포화된 염화암모늄 수용액을 첨가하였다. 생성된 고체를 여과하여 생성물인 N-(4-(4-(3-에틸우레이도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.68 (s, 1H), 7.98 (s, 1H), 7.58 (q, J = 8.2, 8.7 Hz, 4H), 7.37 (s, 1H), 6.55 (s, 1H), 6.22 (s, 1H), 5.75 (s, 1H), 3.14 (d, J = 6.4 Hz, 2H), 2.04 (s, 1H), 1.07 (t, J = 6.7 Hz, 3H), 0.88 - 0.75 (m, 4H).
MS(ESI+) m/z 364 (M+H)+
실시에 432 내지 453
이하, 실시예 432 내지 실시예 453에서는, 실시예 431과 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 432: N-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)모르폴린-4-카르복사미드 (N-(4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)morpholine-4-carboxamide)의 합성
Figure pat00532
1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.57 (s, 1H), 8.73 (s, 1H), 8.00 (s, 1H), 7.73 - 7.56 (m, 4H), 7.37 (d, J = 3.5 Hz, 1H), 6.56 (d, J = 3.2 Hz, 1H), 3.63 (s, 4H), 3.46 (s, 4H), 2.04 (s, 1H), 0.87 - 0.78 (m, 4H).
MS(ESI+) m/z 406 (M+H)+
실시예 433: N-(4-(4-(3- 부틸우레이도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(3- butylureido ) phenyl )-1H- pyrrolo[2,3- b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00533
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.56 (s, 1H), 8.63 (s, 1H), 7.98 (s, 1H), 7.70 - 7.51 (m, 5H), 7.46 - 7.36 (m, 1H), 6.55 (s, 1H), 6.21 (d, J = 5.7 Hz, 1H), 3.19 - 3.07 (m, 2H), 2.05 (s, 1H), 1.37 (ddd, J = 7.0, 14.2, 40.2 Hz, 5H), 0.90 (t, J = 7.2 Hz, 4H), 0.88 - 0.73 (m, 4H).
MS(ESI+) m/z 392 (M+H)+
실시예 434: N-(4-(4-(3-(4- 플루오로페닐 ) 우레이도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(3-(4-fluorophenyl)ureido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00534
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.58 (s, 1H), 9.07 - 8.95 (m, 1H), 8.87 (s, 1H), 8.01 (s, 1H), 7.65 (q, J = 8.6 Hz, 4H), 7.49 (dd, J = 5.3, 8.8 Hz, 2H), 7.39 (s, 1H), 7.13 (t, J = 8.6 Hz, 2H), 6.61 - 6.53 (m, 1H), 3.60 (s, 1H), 2.05 (s, 1H), 1.76 (s, 1H), 1.24 (s, 2H), 0.81 (d, J = 16.8 Hz, 4H).
MS(ESI+) m/z 380 (M+H)+
실시예 435: N-(4-(4-(3-(2,2,2- 트리플루오로에틸 ) 우레이도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(3-(2,2,2-trifluoroethyl)ureido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00535
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.59 (s, 1H), 9.07 (s, 1H), 7.99 (s, 1H), 7.61 (q, J = 8.5 Hz, 4H), 7.38 (d, J = 3.1 Hz, 1H), 6.92 (s, 1H), 6.59 - 6.47 (m, 1H), 3.95 (dd, J = 6.5, 14.9 Hz, 2H), 2.03 (s, 1H), 0.81 (s, 4H).
MS(ESI+) m/z 418 (M+H)+
실시예 436: N-(4-(2- 메틸 -4-(3-(2,2,2- 트리플루오로에틸 ) 우레이도 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(2-methyl-4-(3-(2,2,2-trifluoroethyl)ureido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00536
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.61 (s, 1H), 8.92 (s, 1H), 7.76 (s, 1H), 7.41 (s, 1H), 7.33 (dd, J = 5.7, 8.6 Hz, 2H), 7.17 (d, J = 8.3 Hz, 1H), 6.89 (s, 1H), 6.12 - 5.99 (m, 1H), 3.97 - 3.89 (m, 2H), 2.13 (s, 4H), 2.03 (s, 1H), 0.79 (s, 4H).
MS(ESI+) m/z 432 (M+H)+
실시예 437: N-(4-(4-(3- 시클로프로필우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3- cyclopropylureido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00537
MS(ESI+) m/z 377 (M+H)+
실시예 438: N-(4-(4-(3- 에틸우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3- ethylureido ) phenyl )-7H- pyrrolo[2,3- d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00538
MS(ESI+) m/z 365 (M+H)+
실시예 439: N-(4-(4-(3- 부틸우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3- butylureido ) phenyl )-7H- pyrrolo[2,3- d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00539
MS(ESI+) m/z 393 (M+H)+
실시예 440: N-(4-(4-(3-(3,4- 디플루오로페닐 ) 우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3-(3,4-difluorophenyl)ureido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00540
MS(ESI+) m/z 449 (M+H)+
실시예 441: N-(4-(4-(3-(4- 플루오로페닐 ) 우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3-(4-fluorophenyl)ureido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00541
MS(ESI+) m/z 431 (M+H)+
실시예 442: N-(4-(4-(3-(2,2,2- 트리플루오로에틸 ) 우레이도 ) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(3-(2,2,2-trifluoroethyl)ureido)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00542
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.50 (s, 1H), 7.86 (d, J = 3.9 Hz, 1H), 7.37 - 7.27 (m, 1H), 6.51 (dd, J = 1.9, 3.6 Hz, 1H), 6.44 (t, J = 6.5 Hz, 1H), 6.33 - 6.19 (m, 2H), 3.83 (dq, J = 6.7, 9.8, 16.0 Hz, 3H), 2.15 - 1.88 (m, 3H), 1.68 (d, J = 9.0 Hz, 1H), 0.86 - 0.75 (m, 4H).
MS(ESI+) m/z 422 (M+H)+
실시예 443: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-N-(2,2,2-트리플루오로에틸)-3,6-디히드로피리딘-1(2H)-카르복사미드 (4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(2,2,2-trifluoroethyl)-3,6-dihydropyridine-1(2H)-carboxamide)의 합성
Figure pat00543
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.55 (s, 1H), 7.86 (s, 1H), 7.42 - 7.32 (m, 1H), 7.22 (t, J = 5.8 Hz, 1H), 6.54 (dd, J = 1.9, 3.7 Hz, 1H), 6.33 (s, 1H), 4.10 (s, 2H), 3.93 - 3.81 (m, 3H), 3.61 (t, J = 5.3 Hz, 2H), 2.02 (s, 1H), 0.82 - 0.75 (m, 4H).
MS(ESI+) m/z 408 (M+H)+
실시예 444: N-부틸-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,6-디히드로피리딘-1(2H)-카르복사미드 (N-butyl-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxamide)의 합성
Figure pat00544
MS(ESI+) m/z 382 (M+H)+
실시예 445: N-(4-(1-(1,1- 디옥시티오모르폴린 -4-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1,1-dioxidothiomorpholine-4-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00545
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.87 (s, 1H), 7.34 (s, 1H), 6.56 (s, 1H), 6.34 (s, 1H), 4.03 (d, J = 8.9 Hz, 2H), 3.63 (d, J = 18.8 Hz, 6H), 3.45 (s, 3H), 3.22 - 3.14 (m, 4H), 2.00 (s, 1H), 1.20 (d, J = 25.7 Hz, 2H), 1.04 (d, J = 6.1 Hz, 2H), 0.80 (s, 4H).
MS(ESI+) m/z 444 (M+H)+
실시예 446: N-(4-(1-(모르폴린-4-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(morpholine-4-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00546
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.34 (s, 1H), 6.56 (s, 1H), 6.34 (s, 1H), 3.96 (s, 2H), 3.60 (s, 6H), 3.17 (d, J = 5.2 Hz, 4H), 2.02 (s, 1H), 1.04 (d, J = 5.6 Hz, 2H), 0.80 (s, 4H).
MS(ESI+) m/z 396 (M+H)+
실시예 447: N-( 시아노메틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,6-디히드로피리딘-1(2H)-카르복사미드 (N-(cyanomethyl)-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxamide)의 합성
Figure pat00547
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.85 (s, 1H), 7.34 (s, 1H), 6.54 (s, 1H), 6.31 (s, 1H), 4.12 (s, 2H), 4.03 (d, J = 6.8 Hz, 1H), 3.65 (s, 3H), 3.63 (s, 2H), 2.00 (d, J = 12.2 Hz, 2H), 0.78 (d, J = 13.1 Hz, 4H).
MS(ESI+) m/z 365 (M+H)+
실시예 448: 3-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-N-(2,2,2-트리플루오로에틸)-8-아자바이시클로[3.2.1]옥트-2-엔-8-카르복사미드 (3-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3-b]pyridin -4- yl )-N-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxamide)의 합성
Figure pat00548
MS(ESI+) m/z 434 (M+H)+
실시예 449: N-부틸-3-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-8-아자비시클로[3.2.1]옥트-2-엔-8-카르복사미드 (N-butyl-3-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxamide)의 합성
Figure pat00549
MS(ESI+) m/z 408 (M+H)+
실시예 450: 4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-N-(1-시클로프로필-2,2,2-트리플루오로에틸)-3,6-디하이드로피리딘-1(2H)-카르복사미드 (4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3-b]pyridin -4- yl )-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-3,6-dihydropyridine-1(2H)-carboxamide)의 합성
Figure pat00550
1H NMR (400 MHz, DMSO-d6) δ 10.81 (s, 1H), 10.05 (dd, J = 3.0, 8.9 Hz, 1H), 7.84 (d, J = 4.0 Hz, 1H), 7.81 (d, J = 4.8 Hz, 1H), 6.89 (d, J = 4.1 Hz, 1H), 6.36 (d, J = 4.6 Hz, 1H), 4.43 (d, J = 3.2 Hz, 1H), 4.32 (s, 1H), 4.08 (p, J = 8.7 Hz, 1H), 3.93 (t, J = 5.5 Hz, 1H), 3.80 (t, J = 5.7 Hz, 1H), 2.68 (s, 2H), 1.94 (q, J = 6.2 Hz, 1H), 1.55 (dd, J = 6.6, 12.0 Hz, 1H), 1.16 - 1.10 (m, 1H), 0.92 - 0.86 (m, 4H), 0.72 (dd, J = 5.6, 22.3 Hz, 2H), 0.64 (d, J = 25.9 Hz, 1H), 0.46 - 0.35 (m, 1H).
MS(ESI+) m/z 448 (M+H)+
실시예 451: N-(4-(1-(1H-이미다졸-1-카르보닐)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1H-imidazole-1-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00551
1H NMR (400 MHz, Methanol-d4) δ 11.46 (s, 1H), 10.57 (s, 1H), 8.13 (s, 1H), 7.90 (s, 1H), 7.58 (d, J = 1.4 Hz, 1H), 7.36 (t, J = 3.0 Hz, 1H), 7.06 (s, 1H), 6.60 (d, J = 2.8 Hz, 1H), 6.34 (s, 1H), 4.29 (d, J = 3.6 Hz, 2H), 3.71 (d, J = 6.3 Hz, 2H), 2.72 (s, 2H), 1.99 (s, 1H), 0.85 - 0.69 (m, 4H).
MS(ESI+) m/z 377 (M+H)+
실시예 452: N-(4-(1-(1H-이미다졸-1-카르보닐)-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1H-imidazole-1-carbonyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00552
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.57 (s, 1H), 8.13 (s, 1H), 7.85 (s, 1H), 7.58 (d, J = 1.8 Hz, 1H), 7.38 - 7.30 (m, 1H), 7.07 (s, 1H), 6.59 - 6.50 (m, 1H), 6.10 (s, 1H), 4.37 - 4.22 (m, 2H), 3.70 (s, 2H), 3.14 (s, 1H), 2.00 (d, J = 15.8 Hz, 1H), 0.90 (d, J = 7.0 Hz, 3H), 0.85 - 0.72 (m, 4H).
MS(ESI+) m/z 391 (M+H)+
실시예 453: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-메틸-N-(2,2,2-트리플루오로에틸)-3,6-디하이드로피리딘-1(2H)-카르복사미드 (4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methyl-N-(2,2,2-trifluoroethyl)-3,6-dihydropyridine-1(2H)-carboxamide)의 합성
Figure pat00553
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.56 (s, 1H), 7.83 (s, 1H), 7.39 - 7.30 (m, 1H), 7.25 - 7.16 (m, 1H), 6.46 (dd, J = 2.0, 3.6 Hz, 1H), 6.10 (d, J = 3.5 Hz, 1H), 4.23 (d, J = 18.2 Hz, 1H), 3.99 - 3.84 (m, 3H), 3.62 - 3.49 (m, 2H), 2.94 (s, 1H), 2.03 (d, J = 8.3 Hz, 1H), 0.86 (d, J = 6.9 Hz, 3H), 0.82 - 0.73 (m, 4H).
MS(ESI+) m/z 422 (M+H)+
실시예 454: tert - 부틸4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,6-디히드로피리딘-1(2H)-카르복실레이트 ( tert - butyl 4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate)의 합성
Figure pat00554
[단계 1]
상기 반응식 3로부터 제조한 N-(4-(4,4,5,5-테트라메틸-1,3,2-디옥사보롤란-2-일)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 4.0 g (8.3 mmol)을 DMF/H2O = 2:1 용액에 용해시키고, tert-부틸-4-(((트리플루오로메틸)술포닐)옥시)-3,6-디히드로피리딘-1(2H)-카르복실레이트 3.3 g(10.0 mmol), Pd(PPh3)4 0.9 g(0.8 mmol), 2M K2CO3 수용액 0.57 mL을 넣고, 100 ~110 oC 에서 2시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 물을 첨가, 에틸아세테이트로 추출하였다. 추출한 용액은 무수 황산마그네슘으로 건조하고, 감압 농축하여 잔여물을 수득하였다. 잔여물은 NH-실리카겔 컬럼크로마토그래피 (n-헥산 / 에틸아세테이트 = 5:1)에서 분리하여, tert-부틸4-(6-(시클로프로판카르복사미도)-1-토실-1H-피롤로[2,3-b]피리딘-4-일)-3,6-디히드로피리딘-1-(2H)-카르복실레이트를 수득하였다.
MS(ESI+) m/z 537 (M+H)+
[단계 2]
합성된 물질을 MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 ~ 40 oC에서 4 시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온으로 냉각시키고, 교반하면서 포화된 염화암모늄 수용액을 첨가하였다. 생성된 고체를 여과하여 생성물인 tert-부틸4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-3,6-디히드로피리딘-1(2H)-카르복실레이트를 수득하였다.
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.43 - 7.26 (m, 1H), 6.61 - 6.45 (m, 1H), 6.31 (s, 1H), 4.07 (s, 2H), 3.67 - 3.46 (m, 2H), 2.59 - 2.52 (m, 2H), 2.02 (td, J = 3.7, 7.8 Hz, 1H), 1.44 (s, 9H), 0.80 (dt, J = 5.9, 12.2 Hz, 4H).
MS(ESI+) m/z 383 (M+H)+
실시예 455 내지 461
이하, 실시예 455 내지 실시예 461에서는, 실시예 454와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 455: 시아노메틸4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,6-디히드로피리딘-1(2H)-카르복실레이트 ( cyanomethyl 4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate)의 합성
Figure pat00555
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.56 (s, 1H), 7.87 (s, 1H), 7.41 - 7.30 (m, 1H), 6.56 (dd, J = 1.9, 3.6 Hz, 1H), 6.32 (d, J = 14.8 Hz, 1H), 4.98 (s, 2H), 4.16 (s, 2H), 3.67 (q, J = 5.6, 7.9 Hz, 2H), 2.58 (s, 3H), 2.02 (s, 1H), 0.85 - 0.73 (m, 4H).
MS(ESI+) m/z 366 (M+H)+
실시예 456: tert -부틸 4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-메틸-3,6-디히드로피리딘-1(2H)-카르복실레이트 ( tert - butyl 4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methyl-3,6-dihydropyridine-1(2H)-carboxylate)의 합성
Figure pat00556
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.56 (s, 1H), 7.83 (s, 1H), 7.32 (t, J = 3.1 Hz, 1H), 6.48 (d, J = 3.0 Hz, 1H), 6.08 (s, 1H), 4.25 (s, 1H), 3.88 (s, 1H), 3.68 - 3.37 (m, 2H), 2.92 (s, 1H), 2.01 (s, 1H), 0.86 (d, J = 6.7 Hz, 3H), 0.81 - 0.71 (m, 4H).
MS(ESI+) m/z 397 (M+H)+
실시예 457: tert - 부틸4 -(6-( 시클로프로판카르복사미도 )-5- 메틸 -1H- 피롤로[2,3-b]피리딘 -4-일)-3,6-디히드로피리딘-1(2H)-카르복실레이트 ( tert - butyl 4-(6-(cyclopropanecarboxamido)-5-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate)의 합성
Figure pat00557
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.03 (s, 1H), 7.34 (t, J = 2.9 Hz, 1H), 6.23 (dd, J = 3.5, 1.9 Hz, 1H), 5.66 (s, 1H), 4.03 (s, 2H), 3.61 (d, J = 5.7 Hz, 2H), 2.30 (s, 2H), 2.08 (s, 3H), 1.45 (s, 9H), 0.76 (d, J = 6.2 Hz, 4H).
MS(ESI+) m/z 397 (M+H)+
실시예 458: tert -부틸 4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-에틸-3,6-디히드로피리딘-1(2H)-카르복실레이트 ( tert - butyl 4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-ethyl-3,6-dihydropyridine-1(2H)-carboxylate)의 합성
Figure pat00558
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.55 (s, 1H), 7.83 (s, 1H), 7.42 - 7.25 (m, 1H), 6.58 - 6.48 (m, 1H), 6.11 (s, 1H), 4.33 (dd, J = 19.3, 44.4 Hz, 1H), 4.10 - 3.67 (m, 2H), 3.21 (dd, J = 3.7, 13.1 Hz, 1H), 2.67 (d, J = 1.7 Hz, 1H), 2.02 (s, 1H), 1.44 (s, 9H), 1.22 (d, J = 15.5 Hz, 3H), 0.87 - 0.73 (m, 7H).
MS(ESI+) m/z 411 (M+H)+
실시예 459: tert - 부틸5 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,4-디히드로피리딘-1(2H)-카르복실레이트 ( tert - butyl 5-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,4-dihydropyridine-1(2H)-carboxylate)의 합성
Figure pat00559
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.46 (s, 1H), 7.85 (s, 1H), 7.68 (s, 1H), 7.33 (s, 1H), 6.48 (dd, J = 3.5, 1.9 Hz, 1H), 3.59 (s, 2H), 2.46 (s, 2H), 2.01 (q, J = 6.3 Hz, 1H), 1.93 (t, J = 6.0 Hz, 2H), 0.85 - 0.71 (m, 4H).
MS(ESI+) m/z 383 (M+H)+
실시예 460: tert - 부틸5 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,6-디히드로피리딘-1(2H)-카르복실레이트 ( tert - butyl 5-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate)의 합성
Figure pat00560
1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 10.55 (s, 1H), 7.84 (s, 1H), 7.35 (t, J = 3.0 Hz, 1H), 6.52 (s, 1H), 6.39 (s, 1H), 4.26 (s, 2H), 3.53 (t, J = 5.8 Hz, 2H), 2.34 (td, J = 6.9, 6.3, 2.8 Hz, 2H), 2.02 (tt, J = 7.5, 4.5 Hz, 1H), 1.43 (s, 9H), 0.80 (ddt, J = 10.9, 5.4, 3.0 Hz, 4H).
MS(ESI+) m/z 383 (M+H)+
실시예 461: tert - 부틸3 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-2,5-디히드로-1H-피롤-1-카르복실레이트 ( tert - butyl 3-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate)의 합성
Figure pat00561
MS(ESI+) m/z 369 (M+H)+
실시예 462: N-(4-(4-(3- 에틸티오우레이도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(3- ethylthioureido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00562
N-(4-(4-아미노페닐)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (100 mg)를 피리딘과 교반하였다. 혼합물에 에틸 이소티오시아네이트 4 당량을 넣고, 50 - 60 oC 에서 16시간 동안 교반하였다. 반응이 완료되면 상기 혼합물을 농축 후, MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 ~ 40 oC에서 4 시간동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온으로 냉각시키고, 교반하면서 포화된 염화암모늄 수용액을 첨가하였다. 생성된 고체를 여과하여 생성물인 N-(4-(4-(3-에틸티오우레이도)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.60 (s, 1H), 9.71 (s, 1H), 7.99 (d, J = 23.1 Hz, 2H), 7.63 (dd, J = 8.6, 31.6 Hz, 4H), 7.40 (s, 1H), 6.55 (d, J = 3.5 Hz, 1H), 2.05 (s, 1H), 1.25 - 1.13 (m, 3H), 0.82 (d, J = 7.6 Hz, 4H).
MS(ESI+) m/z 380 (M+H)+
실시예 463 내지 469
이하, 실시예 463 내지 실시예 469에서는, 실시예 462와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 463: N-(4-(4-(3- 부틸티오우레이도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(3- butylthioureido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00563
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.69 (s, 1H), 9.78 (s, 1H), 7.99 (s, 2H), 7.65 (q, J = 8.5 Hz, 3H), 7.41 (d, J = 3.1 Hz, 1H), 6.57 (d, J = 3.3 Hz, 1H), 3.49 (s, 2H), 2.06 (d, J = 13.5 Hz, 1H), 1.60 - 1.49 (m, 2H), 1.34 (q, J = 7.4 Hz, 2H), 1.24 (s, 1H), 0.92 (t, J = 7.2 Hz, 3H), 0.83 (d, J = 6.8 Hz, 4H).
MS(ESI+) m/z 408 (M+H)+
실시예 464: N-(4-(4-(3- 시클로헥실티오우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3-cyclohexylthioureido)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00564
MS(ESI+) m/z 435 (M+H)+
실시예 465: N-(4-(4-(3- 부틸티오우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3- butylthioureido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00565
MS(ESI+) m/z 409 (M+H)+
실시예 466: N-(4-(4-(3- 에틸티오우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3- ethylthioureido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00566
MS(ESI+) m/z 381 (M+H)+
실시예 467: N-(4-(4-(3- 프로필티오우레이도 )페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(3- propylthioureido ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00567
MS(ESI+) m/z 395 (M+H)+
실시예 468: N-(4-(1-( 에틸카르바모티오일 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(ethylcarbamothioyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00568
MS(ESI+) m/z 370 (M+H)+
실시예 469: N-(4-(8-( 에틸카르바모티오일 )-8- 아자비시클로[3.2.1]옥트 -2-엔-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(ethylcarbamothioyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00569
MS(ESI+) m/z 396 (M+H)+
실시예 470: N-(4-(4-(( 시클로프로필메틸 )아미노)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((cyclopropylmethyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 제조
Figure pat00570
N-(4-(4-아미노페닐)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (100 mg)을 디클로로에탄에 용해시키고, 시클로프로판카르브알데히드 3당량, 아세트산 3당량을 넣고 실온에서 30분동안 교반하였다. 반응 혼합물에 나트륨트리아세톡시보로하이드라이드 3당량을 넣고 40 oC 에서 16시간 동안 교반하였다. 반응이 완료되면 상기 혼합물을 농축 후, MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 ~ 40 oC에서 4 시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 디클로로메탄으로 추출하였다. 추출한 용액은 무수황산마그네슘으로 건조하고, 감압농축하여 잔여물을 수득하였다. 잔여물은 prep. TLC (DCM : MeOH = 30 :1) 방법을 통해 목적 화합물 N-(4-(4-((시클로프로필메틸)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
MS(ESI+) m/z 347 (M+H)+
실시예 471 내지 489
이하, 실시예 471 내지 실시예 489 에서는, 실시예 470과 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 471: N-(4-(4-(( 시클로헥실메틸 )아미노)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(( cyclohexylmethyl ) amino ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00571
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.50 (s, 1H), 7.92 (s, 1H), 7.48 (d, J = 8.6 Hz, 2H), 7.32 (dd, J = 2.4, 3.5 Hz, 1H), 6.69 (d, J = 8.5 Hz, 2H), 6.54 (dd, J = 1.9, 3.5 Hz, 1H), 6.02 (t, J = 5.7 Hz, 1H), 3.64 - 3.55 (m, 2H), 2.91 (t, J = 6.2 Hz, 2H), 2.03 (s, 1H), 1.82 - 1.52 (m, 7H), 1.25 - 1.12 (m, 3H), 0.95 (q, J = 12.0, 12.5 Hz, 2H), 0.86 - 0.72 (m, 4H).
MS(ESI+) m/z 389 (M+H)+
실시예 472: N-(4-(4-( 벤질아미노 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-( benzylamino ) phenyl )-1H- pyrrolo[2,3-b]pyridin -6-yl)cyclopropanecarboxamide)의 합성
Figure pat00572
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.50 (s, 1H), 7.91 (s, 1H), 7.46 (d, J = 8.6 Hz, 2H), 7.42 - 7.28 (m, 5H), 7.24 (t, J = 7.3 Hz, 1H), 6.73 (d, J = 8.6 Hz, 2H), 6.63 (t, J = 6.0 Hz, 1H), 6.52 (dd, J = 1.8, 3.5 Hz, 1H), 4.34 (d, J = 6.0 Hz, 2H), 2.02 (s, 1H), 0.83 - 0.72 (m, 4H).
MS(ESI+) m/z 383 (M+H)+
실시예 473: N-(4-(4-((4- 플루오로벤질 )아미노)페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((4- fluorobenzyl ) amino ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00573
MS(ESI+) m/z 402 (M+H)+
실시예 474: N-(4-(4-((3- 플루오로벤질 )아미노)페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3- fluorobenzyl ) amino ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00574
MS(ESI+) m/z 402 (M+H)+
실시예 475: N-(4-(4-((4- 클로로벤질 )아미노)페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((4- chlorobenzyl ) amino ) phenyl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00575
MS(ESI+) m/z 418, 420 (M+H)+
실시예 476: N-(4-(4-((3-히드록시프로필)아미노)페닐)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-((3-hydroxypropyl)amino)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00576
MS(ESI+) m/z 352 (M+H)+
실시예 477: N-(4-(1-(2- 시아노에틸 )-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(2- cyanoethyl )-1H- pyrazol -4- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00577
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.53 (s, 1H), 8.50 (s, 1H), 8.06 (d, J = 9.1 Hz, 2H), 7.48 - 7.35 (m, 1H), 7.00 (s, 1H), 6.72 (d, J = 4.1 Hz, 1H), 4.57 - 4.45 (m, 2H), 3.22 - 3.11 (m, 2H), 2.05 (s, 1H), 0.82 (d, J = 12.2 Hz, 4H).
MS(ESI+) m/z 321 (M+H)+
실시예 478: N-(4-(1-( 시클로프로필메틸 )-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-( cyclopropylmethyl )-1H- pyrazol -4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00578
1H NMR (400 MHz, DMSO-d6) δ 11.42 (d, J = 12.3 Hz, 1H), 10.51 (s, 1H), 8.39 (s, 1H), 8.01 (d, J = 32.6 Hz, 2H), 7.48 - 7.31 (m, 1H), 6.72 (s, 1H), 4.06 (d, J = 7.7 Hz, 2H), 2.04 (s, 1H), 1.33 (s, 1H), 0.89 - 0.74 (m, 4H), 0.62 - 0.38 (m, 4H).
MS(ESI+) m/z 322 (M+H)+
실시예 479: N-(4-(1- 벤질 -1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(1- benzyl -1H- pyrazol -4- yl )-1H- pyrrolo[2,3- b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00579
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.50 (s, 1H), 8.54 (s, 1H), 8.09 - 7.91 (m, 3H), 7.35 (d, J = 13.5 Hz, 8H), 7.23 (s, 1H), 6.71 (s, 1H), 5.42 (d, J = 4.1 Hz, 2H), 2.03 (s, 1H), 0.82 (s, 4H).
MS(ESI+) m/z 358 (M+H)+
실시예 480: N-(4-(1-(2- 시아노에틸 )-3,5-디메틸-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoethyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00580
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.55 (s, 1H), 7.72 (s, 1H), 7.32 (s, 1H), 6.14 (s, 1H), 4.33 (d, J = 5.9 Hz, 2H), 3.06 (d, J = 5.9 Hz, 2H), 2.27 - 2.17 (m, 3H), 2.10 (s, 3H), 2.02 (s, 1H), 0.78 (d, J = 12.9 Hz, 4H).
MS(ESI+) m/z 349 (M+H)+
실시예 481: N-(4-(1- 벤질 -1H-1,2,3- 트리아졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1- benzyl -1H-1,2,3- triazol -4- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00581
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.58 (s, 1H), 8.93 (s, 1H), 8.40 (s, 1H), 7.51 - 7.30 (m, 6H), 6.88 (dd, J = 3.5, 1.9 Hz, 1H), 5.69 (s, 2H) 2.10 - 1.95 (m, 1H), 0.96 - 0.72 (m, 4H).
MS(ESI+) m/z 421 (M+H)+
실시예 482: N-(4-(1-((6- 시아노피리딘 -3-일) 메틸 )-1H- 피라졸 -4-일)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(1-((6-cyanopyridin-3-yl)methyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00582
1H NMR (400 MHz, DMSO-d6) δ 11.92 (s, 1H), 10.42 (s, 1H), 9.16 (s, 1H), 8.78 (s, 1H), 8.71 (d, J = 2.1 Hz, 1H), 8.29 (d, J = 3.3 Hz, 1H), 7.88 - 7.76 (m, 2H), 7.43 (d, J = 3.8 Hz, 1H), 6.87 (d, J = 3.8 Hz, 1H), 5.60 (d, J = 6.2 Hz, 2H), 2.20 (s, 1H), 0.80 (ddt, J = 3.0, 4.9, 10.7 Hz, 4H).
MS(ESI+) m/z 385 (M+H)+
실시예 483: N-(4-(1-(2- 시아노에틸 )-1H-피롤-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(2- cyanoethyl )-1H- pyrrol -3- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00583
1H NMR (400 MHz, DMSO-d6) δ 11.30 (s, 1H), 10.44 (s, 1H), 8.01 (s, 1H), 7.56 (d, J = 2.1 Hz, 1H), 7.31 (d, J = 2.5 Hz, 1H), 6.98 (t, J = 2.5 Hz, 1H), 6.71 (d, J = 3.2 Hz, 1H), 6.54 (d, J = 2.5 Hz, 1H), 4.27 (t, J = 6.5 Hz, 2H), 3.09 (t, J = 6.4 Hz, 2H), 2.03 (s, 1H), 0.83 - 0.76 (m, 4H).
MS(ESI+) m/z 320 (M+H)+
실시예 484: N-(4-(1-(2- 모르폴리노에틸 )-2,5- 디히드로 -1H-피롤-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(2-morpholinoethyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00584
1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 10.61 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 3.1 Hz, 1H), 6.81 - 6.64 (m, 2H), 4.55 (d, J = 10.5 Hz, 2H), 4.37 (s, 2H), 4.19 (t, J = 6.7 Hz, 2H), 3.57 (d, J = 4.7 Hz, 4H), 2.59 (d, J = 6.2 Hz, 2H), 2.45 (d, J = 4.6 Hz, 2H), 2.03 (s, 1H), 0.84 - 0.74 (m, 4H).
MS(ESI+) m/z 382 (M+H)+
실시예 485: N-(4-(1-(2- 시아노에틸 )-2,5- 디하이드로 -1H-피롤-3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoethyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00585
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.55 (s, 1H), 7.80 (s, 1H), 7.38 (t, J = 3.0 Hz, 1H), 6.67 - 6.57 (m, 2H), 3.93 (q, J = 3.7 Hz, 2H), 3.73 (td, J = 2.1, 4.5 Hz, 2H), 2.94 (t, J = 6.7 Hz, 2H), 2.73 (t, J = 6.7 Hz, 2H), 2.02 (tt, J = 4.5, 7.7 Hz, 1H), 0.80 (ddd, J = 2.8, 5.3, 11.3 Hz, 4H).
MS(ESI+) m/z 322 (M+H)+
실시예 486: N-(4-(1-(2- 시아노에틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-cyanoethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00586
1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.50 (s, 1H), 7.86 (s, 1H), 7.33 (d, J = 2.7 Hz, 1H), 6.54 (d, J = 3.5 Hz, 1H), 6.32 (s, 1H), 3.23 (t, J = 3.1 Hz, 2H), 2.73 (dd, J = 4.5, 7.5 Hz, 5H), 2.02 (s, 1H), 0.82 - 0.75 (m, 4H).
MS(ESI+) m/z 336 (M+H)+
실시예 487: N-(4-(1-((3- 메틸옥세탄 -3-일) 메틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]사이클로프로판카복스아마이드 (N-(4-(1-((3-methyloxetan-3-yl)methyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00587
MS(ESI+) m/z 367 (M+H)+
실시예 488: N-(4-(1-( 이소티아졸 -5- 일메틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(isothiazol-5-ylmethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00588
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.53 (s, 1H), 8.50 (d, J = 1.6 Hz, 1H), 7.86 (s, 1H), 7.33 (d, J = 2.1 Hz, 2H), 6.55 (d, J = 2.7 Hz, 1H), 6.33 (s, 1H), 3.29 (d, J = 3.4 Hz, 2H), 2.77 (t, J = 5.6 Hz, 2H), 2.56 (s, 2H), 2.01 (d, J = 4.1 Hz, 1H), 0.88 - 0.72 (m, 4H).
MS(ESI+) m/z 380 (M+H)+
실시예 489: N-(4-(1-((2,2- 디플루오로시클로프로필 ) 메틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-((2,2-difluorocyclopropyl)methyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00589
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.52 (s, 1H), 7.85 (s, 1H), 7.35 - 7.29 (m, 1H), 6.54 (dd, J = 3.5, 1.8 Hz, 1H), 6.33 (d, J = 3.4 Hz, 1H), 3.25 - 3.19 (m, 2H), 2.72 (dp, J = 16.1, 5.4 Hz, 3H), 2.50 (m, 3H), 2.01 (s, 1H), 1.90 (tt, J = 13.8, 6.9 Hz, 1H), 1.62 (qt, J = 12.1, 5.9 Hz, 1H), 1.19 (dd, J = 7.9, 3.8 Hz, 1H), 0.87 - 0.72 (m, 4H)
MS(ESI+) m/z 373 (M+H)+
실시예 490: N-(4-(1-(-3- 시아노시클로부틸 )-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-cyanocyclobutyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00590
합성된 N-(4-(4-아미노시클로헥스-1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 1.0 g(3.37 mmol), 3-옥소사이클로부테인-1-카보니트릴을 THF 용액에 용해시키고, NaBH(OAc)3와 DIPEA를 넣고, 실온에서 하루 동안 교반하였다. 반응이 완료되면 물을 첨가, 다이클로로메탄으로 추출하였다. 추출한 용액은 무수황산마그네슘으로 건조하고, 감압 농축하여 잔여물을 수득하였다. 잔여물은 실리카겔 컬럼크로마토그래피로 분리하여 N-(4-(4-((1-(3,5-디플루오로벤조일)피페리딘-4-일)아미노)시클로헥스-1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
MS(ESI+) m/z 362 (M+H)+
실시예 491 내지 518
이하, 실시예 491 내지 실시예 518에서는, 실시예 490과 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 491: N-(4-(4-((1-(3,5- 디플루오로벤조일 )피페리딘-4-일)아미노) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(3,5-difluorobenzoyl)piperidin-4-yl)amino)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00591
1H NMR (400MHz, DMSO-d6) δ 11.35 (s, 1H), 10.48 (s, 1H), 7.82 (s, 1H), 7.38 - 7.20 (m, 2H), 7.17 - 7.10 (m, 2H), 6.48 (dd, J=3.5, 1.8 Hz, 1H), 6.23 (s, 1H), 4.28 (s, 1H), 3.47 (s, 1H), 2.98 (s, 3H), 2.00 (s, 3H), 1.81 (s, 1H), 1.48 (s, 2H), 1.25 (d, J=9.2 Hz, 5H), 0.82-0.74 (m, 4H).
MS(ESI+) m/z 520 (M+H)+
실시예 492: N-(4-(4-((1-( 시클로헥산카르보닐 )피페리딘-4-일)아미노) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(cyclohexanecarbonyl)piperidin-4-yl)amino)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00592
1H NMR(400MHz,DMSO-d6) δ 11.35 (s,1H), 10.48 (s,1H), 7.82 (s,1H), 7.30 (t,J=3.0Hz, 1H), 6.49 (dd,J=3.6, 1.9Hz, 1H), 6.22 (s,1H), 4.26 (d, J=13.7Hz, 1H), 3.88 (d, J=13.5Hz, 1H), 3.56(t, J=7.0Hz, 1H), 3.14 (dd, J=7.5, 5.6Hz, 1H), 2.19 (d, J=6.7Hz, 1H), 2.01 (s, 4H), 1.70 (d, J=11.1Hz, 4H), 1.61 (t, J=6.9Hz, 6H), 1.30 (s, 6H), 1.18 (d, J=9.8Hz, 2H), 1.07 (t, J=7.2Hz, 2H), 0.82 - 0.77 (m, 4H)
MS(ESI+) m/z 490 (M+H)+
실시예 493: N-(4-(4-((1-(2- 플루오로이소니코티노일 )피페리딘-4-일)아미노)시클로헥스-1-엔-1-일)-1H-피롤로[2,3-b]사이클로프로판 카르복사미드 (N-(4-(4-((1-(2-fluoroisonicotinoyl)piperidin-4-yl)amino)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00593
1H NMR (400MHz, DMSO-d6) δ 11.36 (s, 1H), 10.48 (s, 1H), 8.33 (d, J=5.0Hz, 1H), 7.82 (s, 1H), 7.32 (dt, J=18.3, 3.9Hz, 2H), 7.23 (s,1H), 6.49 (dd, J=3.6, 1.9Hz, 1H), 6.22 (s, 1H), 4.32 (d,J=12.7Hz, 1H), 3.43 (d, J=13.8Hz, 1H), 3.04 (dt, J=39.7, 12.3Hz, 4H), 1.98 (d, J=22.7Hz, 4H), 0.84 - 0.75 (m, 4H)
MS(ESI+) m/z 503 (M+H)+
실시예 494: N-(4-(4-((1-(4- 니트로벤조일 )피페리딘-4-일)아미노) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판 카르복사미드 (N-(4-(4-((1-(4-nitrobenzoyl)piperidin-4-yl)amino)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00594
1H NMR (400MHz, DMSO-d6) δ 11.35 (d, J=3.2Hz, 1H), 10.48 (s, 1H), 8.32-8.25 (m, 2H), 7.82 (s, 1H), 7.71-7.59 (m, 2H), 7.29 (t, J=3.1Hz, 1H), 6.48 (dd, J=3.5, 1.9Hz, 1H), 6.22 (s,1H), 4.32 (d, J=12.4Hz, 1H), 3.43 (d, J=13.3Hz, 1H), 3.03 (d, J=52.9Hz, 4H), 2.00 (d, J=7.2Hz, 4H), 1.78(s, 1H), 1.47 (s, 2H), 1.25 (d,J=17.8Hz, 4H), 0.85 - 0.73 (m, 4H)
MS(ESI+) m/z 529 (M+H)+
실시예 495: N-(4-(4-((1-(3,5- 디플루오로벤조일 ) 아제티딘 -3-일)아미노) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(3,5-difluorobenzoyl)azetidin-3-yl)amino)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00595
1H NMR (400MHz, DMSO-d6) δ 11.35 (s, 1H), 10.47 (s, 1H), 7.43 (tt, J=9.5, 2.5Hz, 1H), 7.30 (dq, J=5.8, 2.1Hz, 3H), 7.19 -7.12 (m, 1H), 6.48 (t, J=2.7Hz, 1H), 6.21 (d, J=4.1Hz, 1H), 4.47 (d, J=8.4Hz, 1H), 4.22 (d, J=10.5Hz, 1H), 4.03 (s, 1H), 3.78 (dd, J=7.0, 3.8Hz, 2H), 3.63 (t, J=7.0Hz, 1H), 3.01 (qd, J=7.2, 5.3Hz, 1H), 1.91 (d, J=6.9Hz, 1H), 0.83 - 0.72 (m, 4H)
MS(ESI+) m/z 492 (M+H)+
실시예 496: N-(4-(4-((1-(2- 플루오로이소니코티노일 ) 아제티딘 -3-일)아미노)시클로헥스-1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판 카르복사미드 (N-(4-(4-((1-(2-fluoroisonicotinoyl)azetidin-3-yl)amino)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00596
1H NMR (400MHz, DMSO-d6) δ 11.35 (s, 1H),10.48(s, 1H), 8.34 (dd, J=22.8, 5.1Hz, 1H), 7.82 (s, 1H), 7.52 (dt, J=5.1, 1.6Hz, 1H), 7.33 (t, J=1.7Hz, 1H), 7.29 (t, J=3.1Hz, 1H), 6.47 (dt, J=3.7, 2.0Hz, 1H), 6.21 (s,1H), 4.46 (td,J=7.6, 6.5, 3.9Hz, 1H), 4.24 (d, J=10.7Hz, 1H), 4.04-4.01 (m, 1H), 3.79 (dt, J=7.7, 4.2Hz, 2H), 3.00 (ddd, J=8.6, 6.9, 5.3Hz, 1H), 2.80 (s,1H), 2.18 (t, J=3.4Hz, 1H), 2.03-1.99 (m, 2H), 1.91 (d, J = 5.9Hz, 1H), 0.82 - 0.74 (m, 4H)
MS(ESI+) m/z 475 (M+H)+
실시예 497: N-(4-(4-((1-(2- 메톡시이소니코티노일 ) 아제티딘 -3-일)아미노) 시클로헥스 -1-엔-1-일)-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판 카르복사미드 (N-(4-(4-((1-(2-methoxyisonicotinoyl)azetidin-3-yl)amino)cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00597
1H NMR (400MHz, DMSO-d6) δ 11.35 (s, 1H), 10.48 (s, 1H), 8.27 (d, J=5.3Hz, 1H), 7.81(s, 1H), 7.33-7.26 (m, 1H), 7.12 (dd, J=5.2, 1.4Hz, 1H), 6.92 (t, J=1.0Hz, 1H), 6.53-6.43 (m, 1H), 6.21 (s, 1H), 4.43 (s, 1H), 4.23 (s, 1H), 3.99 (s, 1H), 3.78 (s, 2H), 2.81 (s, 1H), 2.00 (d, J=5.4Hz, 2H), 1.91 (s, 1H), 1.48 (s, 2H), 0.81-0.74 (m, 4H)
MS(ESI+) m/z 487 (M+H)+
실시예 498: 4 -((4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-2-플루오로페닐)아미노)-N-페닐피페리딘-1-카르복사미드 (4-((4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-2-fluorophenyl)amino)-N-phenylpiperidine-1-carboxamide)의 합성
Figure pat00598
1H NMR (400MHz, DMSO-d6) δ 11.45 (s, 1H), 10.54 (s, 1H), 8.52 (s, 1H), 7.95 (s, 1H), 7.51-7.45 (m, 2H), 7.42-7.33 (m, 3H), 7.25-7.19 (m, 2H), 7.00 (t, J=8.8Hz, 1H), 6.94-6.87 (m, 1H), 6.56 (dd, J=3.5, 1.9Hz, 1H), 5.61 (d, J=7.9Hz, 1H), 4.15 (d, J=13.3Hz, 2H), 3.61 (s,1H), 2.96 (t, J=12.5Hz, 2H), 2.04 (s, 1H), 1.94 (t, J=14.5Hz, 2H), 1.52-1.42 (m, 3H), 1.23 (s, 6H), 0.82 (dd, J=8.8, 5.0Hz, 4H).
MS(ESI+) m/z 513 (M+H)+
실시예 499: N-(4-(4-((1-(3,5- 디플루오로벤조일 )피페리딘-4-일)아미노)-3-플루오로페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(3,5-difluorobenzoyl)piperidin-4-yl)amino)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00599
MS(ESI+) m/z 534 (M+H)+
실시예 500: N-(4-(3- 플루오로 -4-((1-(2- 플루오로이소니코티노일 )피페리딘-4-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(3-fluoro-4-((1-(2-fluoroisonicotinoyl)piperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00600
1H NMR (400MHz, DMSO-d6) δ 11.45 (s, 1H), 10.55 (s, 1H), 8.35 (d, J=5.0Hz, 1H), 7.94 (s, 1H), 7.42-7.28 (m, 3H), 7.24 (s, 1H), 6.99 (s, 1H), 6.58-6.48 (m, 1H), 5.55 (d, J=9.0Hz, 1H), 5.32 (s, 1H), 2.01 (t, J=7.5Hz, 4H), 1.91 (s, 1H), 1.56-1.39 (m, 4H), 1.23 (s, 9H), 0.83 (d, J=14.1Hz, 4H).
MS(ESI+) m/z 517 (M+H)+
실시예 501: 4 -((4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-2-플루오로페닐)아미노)-N-(2,4-디플루오로페닐)피페리딘-1-카르복사미드 (4-((4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-2-fluorophenyl)amino)-N-(2,4-difluorophenyl)piperidine-1-carboxamide)의 합성
Figure pat00601
1H NMR (400MHz, DMSO-d6) δ 11.48 (s,1H), 10.58 (s, 1H), 8.34 (s, 1H), 7.95 (s, 1H), 7.42-7.33 (m, 5H), 7.31-7.17 (m, 3H), 7.00 (q, J=8.5Hz, 2H), 6.59-6.50(m, 1H), 5.68-5.60 (m, 1H), 4.86-4.73 (m, 1H), 4.10 (d, J=13.3Hz, 2H), 3.60 (s, 2H), 2.96 (t, J=12.6Hz, 2H), 2.18 (t, J=7.4Hz, 1H), 0.86-0.78 (m, 6H).
MS(ESI+) m/z 549 (M+H)+
실시예 502: N-(4-(4-((2S)-1-(3,5- 디플루오로벤조일 )-2- 메틸피페리딘 -4-일)아미노)페닐)-1H-피롤로[2,3-b]-시클로프로판카르복사미드 (N-(4-(4-(((2S)-1-(3,5-difluorobenzoyl)-2-methylpiperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00602
MS(ESI+) m/z 530 (M+H)+
실시예 503: N-(4-(4-(((2S)-1-(2- 플루오로이소니코티노일 )-2- 메틸피페리딘 -4-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((2S)-1-(2-fluoroisonicotinoyl)-2-methylpiperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00603
MS(ESI+) m/z 513 (M+H)+
실시예 504: (2S)-4-((4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)페닐)아미노)-2-메틸-N-(2,2,2-트리플루오로에틸)피페리딘-1-카르복사미드 ((2S)-4-((4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3-b]pyridin -4-yl)phenyl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)piperidine-1-carboxamide)의 합성
Figure pat00604
1H NMR (400MHz, DMSO-d6) δ 11.40 (s, 1H), 10.53 (s, 1H), 7.94 (s, 1H), 7.54-7.47 (m, 2H), 7.33 (dd, J=3.5, 2.5Hz, 1H), 6.75 (dd, J=8.9, 3.1Hz, 2H), 6.55 (td, J=3.4, 1.9Hz, 1H), 3.93-3.77 (m, 3H), 3.59 (d, J=2.8Hz, 1H), 2.05 - 2.00 (m, 1H), 1.95-1.80 (m, 2H), 1.66 (dd, J=30.6, 12.3Hz, 2H), 1.23 (s, 2H), 1.17 (d, J=6.7Hz, 2H), 0.83-0.77 (m, 4H).
MS(ESI+) m/z 515 (M+H)+
실시예 505: 4-((4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-2-플루오로페닐)아미노)-N-(2,2,2-트리플루오로에틸)피페리딘-1-카르복사미드 (4-((4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3-b]pyridin -4- yl )-2-fluorophenyl)amino)-N-(2,2,2-trifluoroethyl)piperidine-1-carboxamide)의 합성
Figure pat00605
1H NMR (400MHz, DMSO-d6) δ 11.47 (s, 1H), 10.58 (s, 1H), 7.95(s, 1H), 7.40-7.34 (m, 3H), 7.17 (t, J=6Hz, 1H), 6.99 (t, J=8.8Hz, 1H), 6.55 (m, 1H), 5.63 (d, J=8.4, 1H), 4.02 (d, J=13.6Hz, 2H), 3.87 (m, 2H), 3.57 (m, 1H), 2.90 (t, J=12.4Hz, 2H), 2.03 (m, 1H), 1.91 (d, J=10.8Hz, 2H), 1.42 (m, 2H), 0.84 (m, 4H).
MS(ESI+) m/z 519 (M+H)+
실시예 506: (2S)-4-((4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아미노)-N-(2,4-디플루오로페닐)-2-메틸피페리딘-1-카르복사미드 ((2S)-4-((4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)amino)-N-(2,4-difluorophenyl)-2-methylpiperidine-1-carboxamide)의 합성
Figure pat00606
MS(ESI+) m/z 545 (M+H)+
실시예 507: N-(4-(4-((1- 이소니코티노일피페리딘 -4-일)아미노)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1-isonicotinoylpiperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00607
MS(ESI+) m/z 481 (M+H)+
실시예 508: N-(4-(4-((1-(3,5- 디플루오로벤조일 )피페리딘-4-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(3,5-difluorobenzoyl)piperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00608
1H NMR (400 MHz, DMSO-d 6) δ 11.40 (s, 1H), 10.52 (s, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.56 -7.30 (m, 4H), 7.17 (dt, J = 5.8, 2.2 Hz, 2H), 6.82 - 6.70 (m, 2H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 5.94 (d, J = 7.7 Hz, 1H), 4.32 (d, J = 13.3 Hz, 1H), 3.69 - 3.49 (m, 3H), 3.16 (d, J = 46.7 Hz, 3H), 2.03 (s, 2H), 1.91 (s, 1H), 0.82 - 0.73 (m, 4H).
MS(ESI+) m/z 516 (M+H)+
실시예 509: N-(4-(4-((1-(2- 플루오로이소니코티노일 )피페리딘-4-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(2-fluoroisonicotinoyl)piperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00609
1H NMR (400 MHz, DMSO-d 6) δ 11.40 (s, 1H), 10.52 (s, 1H), 8.35 (d, J = 5.0 Hz, 1H), 7.93 (s, 1H), 7.53 - 7.45 (m, 2H), 7.37 (dt, J = 4.9, 1.8 Hz, 1H), 7.33 (dd, J = 3.5, 2.5 Hz, 1H), 7.26 (t, J = 1.5 Hz, 1H), 6.80 - 6.73 (m, 2H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 5.96 (d, J = 7.8 Hz, 1H), 4.33 (d, J = 13.2 Hz, 1H), 3.63 (s, 1H), 3.47 (d, J = 13.9 Hz, 1H), 3.22 (t, J = 12.0 Hz, 1H), 3.13 (t, J = 11.5 Hz, 1H), 2.06 (d, J = 15.0 Hz, 2H), 1.93 (s, 1H), 1.50 - 1.31 (m, 2H), 0.79 (m, 4H).
MS(ESI+) m/z 499 (M+H)+
실시예 510: N-(4-(4-((1-(3,5- 디플루오로벤조일 ) 아제티딘 -3-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(3,5-difluorobenzoyl)azetidin-3-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00610
1H NMR (400 MHz, DMSO-d 6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.94 (s, 1H), 7.57 - 7.49 (m, 4H), 7.46 (tt, J = 9.2, 2.4 Hz, 2H), 7.34 (dt, J = 6.2, 2.1 Hz, 3H), 6.68 (dd, J = 11.8, 7.5 Hz, 3H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 4.72 (t, J = 7.9 Hz, 1H), 4.46 (t, J = 8.8 Hz, 1H), 4.37 - 4.27 (m, 1H), 4.13 (dd, J = 8.6, 4.9 Hz, 1H), 3.93 (dd, J = 10.4, 5.0 Hz, 1H), 2.03 (s, 1H), 0.82 - 0.75 (m, 4H).
MS(ESI+) m/z 488 (M+H)+
실시예 511: 4 -((4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아미노)-N-(2,4-디플루오로페닐)피페리딘-1-카르복사미드 (4-((4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)amino)-N-(2,4-difluorophenyl)piperidine-1-carboxamide)의 합성
Figure pat00611
1H NMR (400 MHz, DMSO-d 6) δ 11.40 (s, 1H), 10.53 (s, 1H), 8.94 (d, J = 2.2 Hz, 1H), 8.34 (s, 1H), 8.10 (td, J = 9.2, 6.1 Hz, 1H), 7.94 (d, J = 4.3 Hz, 1H), 7.50 (d, J = 8.6 Hz, 2H), 7.35 - 7.30 (m, 1H), 7.24 (ddd, J = 10.7, 9.1, 2.9 Hz, 1H), 7.08 - 6.93 (m, 1H), 6.76 (d, J = 8.7 Hz, 2H), 6.55 (dd, J = 3.5, 1.9 Hz, 1H), 5.96 (d, J = 8.1 Hz, 1H), 4.03 (d, J = 13.4 Hz, 2H), 3.55 (d, J = 9.8 Hz, 1H), 3.03 (t, J = 11.7 Hz, 2H), 2.11 - 1.92 (m, 3H), 1.41 - 1.31 (m, 2H), 0.85 - 0.71 (m, 4H).
MS(ESI+) m/z 531 (M+H)+
실시예 512: 4 -((4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아미노)-N-(2,2,2-트리플루오로에틸)피페리딘-1-카르복사미드 (4-((4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)amino)-N-(2,2,2-trifluoroethyl)piperidine-1-carboxamide)의 합성
Figure pat00612
1H NMR (400 MHz, DMSO-d 6) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.93 (s, 1H), 7.49 (d, J = 8.6 Hz, 2H), 7.33 (dd, J = 3.5, 2.5 Hz, 1H), 7.16 (t, J = 6.2 Hz, 1H), 6.74 (d, J = 8.5 Hz, 2H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 5.92 (d, J = 8.1 Hz, 1H), 3.93 (d, J = 13.4 Hz, 2H), 3.84 (dtd, J = 16.1, 9.7, 6.5 Hz, 3H), 3.51 (s, 1H), 2.94 (t, J = 12.4 Hz, 2H), 2.05 (d, J = 17.6 Hz, 1H), 1.92 (d, J = 12.2 Hz, 2H), 0.84-0.76 (m, 4H).
MS(ESI+) m/z 501 (M+H)+
실시예 513: 3 -((4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아미노)-N-(2,4-디플루오로페닐)아제티딘-1-카르복사미드 (3-((4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)amino)-N-(2,4-difluorophenyl)azetidine-1-carboxamide)의 합성
Figure pat00613
1H NMR (400 MHz, DMSO-d 6) δ 11.42 (s, 1H), 10.54 (s, 1H), 8.27 (s, 1H), 7.95 (s, 1H), 7.53 (dq, J = 8.9, 3.1 Hz, 3H), 7.34 (dd, J = 3.5, 2.5 Hz, 1H), 7.26 (ddd, J = 10.8, 9.0, 2.9 Hz, 1H), 7.07 - 6.97 (m, 1H), 6.69 (d, J = 8.8 Hz, 3H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 4.32 (m, 3H), 3.79 (dd, J = 8.2, 4.1 Hz, 2H), 2.03 (s, 1H), 0.84 - 0.76 (m, 4H).
MS(ESI+) m/z 503 (M+H)+
실시예 514: 3 -((4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아미노)-N-(2,2,2-트리플루오로에틸)아제티딘-1-카르복사미드 (3-((4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)amino)-N-(2,2,2-trifluoroethyl)azetidine-1-carboxamide)의 합성
Figure pat00614
1H NMR (400 MHz, DMSO-d 6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.95 (d, J = 2.9 Hz, 2H), 7.52 (d, J = 8.6 Hz, 2H), 7.34 (dd, J = 3.5, 2.5 Hz, 1H), 7.08 (t, J = 6.3 Hz, 1H), 6.67 (d, J = 8.7 Hz, 2H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 4.26 - 4.22 (m, 2H), 3.86 - 3.72 (m, 3H), 3.71 - 3.65 (m, 2H), 2.03 (s, 1H), 0.87-076 (m, 4H).
MS(ESI+) m/z 473 (M+H)+
실시예 515: N-(4-(4-((1-(2- 시아노아세틸 ) 아제티딘 -3-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(2-cyanoacetyl)azetidin-3-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00615
MS(ESI+) m/z 415 (M+H)+
실시예 516: N-(4-(4-((1-(2- 시아노아세틸 )피페리딘-4-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(2-cyanoacetyl)piperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00616
MS(ESI+) m/z 443 (M+H)+
실시예 517: N-(4-(4-((1-(3,3,3- 트리플루오로프로파노일 ) 아제티딘 -3-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(3,3,3-trifluoropropanoyl)azetidin-3-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00617
1H NMR (400 MHz, DMSO-d 6) δ 11.42 (s, 1H), 10.54 (s, 1H), 7.95 (s, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 3.0 Hz, 1H), 6.67 (d, J = 8.3 Hz, 3H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 4.55 (t, J = 7.7 Hz, 1H), 4.29 (d, J = 6.2 Hz, 2H), 4.03 - 3.90 (m, 1H), 3.75 (d, J = 5.3 Hz, 1H), 3.40 (m, 2H), 2.03 (s, 1H), 0.84 - 0.76 (m, 4H).
MS(ESI+) m/z 458 (M+H)+
실시예 518: N-(4-(4-((1-(3,3,3- 트리플루오로프로파노일 )피페리딘-4-일)아미노)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((1-(3,3,3-trifluoropropanoyl)piperidin-4-yl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00618
1H NMR (400 MHz, DMSO-d 6) δ 11.39 (s, 1H), 10.52 (s, 1H), 7.94 (s, 1H), 7.50 (d, J = 8.6 Hz, 2H), 7.33 (dd, J = 3.5, 2.5 Hz, 1H), 6.76 (d, J = 8.6 Hz, 2H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 5.95 (d, J = 8.0 Hz, 1H), 4.25 (d, J = 13.2 Hz, 1H), 3.82 (d, J = 13.8 Hz, 1H), 3.76 - 3.53 (m, 3H), 3.21 (t, J = 11.9 Hz, 1H), 2.90 (t, J = 11.3 Hz, 1H), 2.05 - 1.90 (m, 3H), 1.44 - 1.22 (m, 2H), 0.85 - 0.76 (m, 4H).
MS(ESI+) m/z 486 (M+H)+
실시예 519: N-(4-(4-(2- 시아노아세틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- cyanoacetyl ) phenyl )-1H- pyrrolo[2,3- b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00619
상기 반응식 3로부터 제조한 N-(4-(4,4,5,5-테트라메틸-1,3,2-디옥사보롤란-2-일)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 1.0 g (2.1 mmol)을 DMF/H2O = 2:1 용액에 용해시키고, 3-(4-브로모페닐)-3-옥소프로판니트릴 0.6 g (2.5 mmol), Pd(PPh3)4 0.2 g(0.2 mmol), 2M K2CO3 수용액 0.15 mL을 넣고, 100 ~ 110 oC 에서 2시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 물을 첨가, 에틸아세테이트로 추출하였다. 추출한 용액은 무수 황산마그네슘으로 건조하고, 감압 농축하여 잔여물을 수득하였다. 잔여물은 NH-실리카겔 컬럼크로마토그래피 (n-헥산 / 에틸아세테이트 = 5:1)에서 분리하여, N-(4-(4-(2-시아노아세틸)페닐)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 합성하였다. 합성된 물질을 MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 ~ 40 oC에서 4 시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온으로 냉각시키고, 교반하면서 포화된 염화암모늄 수용액을 첨가하였다. 생성된 고체를 여과하여 생성물인 N-(4-(4-(2-시아노아세틸)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
MS(ESI+) m/z 345 (M+H)+
실시예 520 내지 598
이하, 실시예 520 내지 실시예 598에서는, 실시예 519와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 520: N-(4-(4-(1,1- 디옥시도티오모르폴린 -4-카르보닐)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(1,1-dioxidothiomorpholine-4-carbonyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00620
MS(ESI+) m/z 439 (M+H)+
실시예 521: N-(4-(4-( 티오모르폴린 -4-카르보닐)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( thiomorpholine -4- carbonyl ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00621
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.66 (s, 1H), 8.17 - 8.01 (m, 1H), 7.78 (d, J = 7.7 Hz, 2H), 7.57 (d, J = 7.7 Hz, 2H), 7.43 (s, 1H), 6.56 (s, 1H), 3.76 (d, J = 100.0 Hz, 6H), 2.76 - 2.61 (m, 6H), 2.07 (d, J = 13.0 Hz, 1H), 0.80 (d, J = 12.3 Hz, 4H).
MS(ESI+) m/z 407 (M+H)+
실시예 522: N-(4-(2- 메틸 -4-(모르폴린-4-카르보닐)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(2- methyl -4-( morpholine -4-carbonyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00622
MS(ESI+) m/z 405 (M+H)+
실시예 523: N-( 시아노메틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)벤즈아미드 (N-( cyanomethyl )-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)benzamide)의 합성
Figure pat00623
1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 10.67 (s, 1H), 9.32 (s, 1H), 8.09 (s, 1H), 8.04 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 3.3 Hz, 1H), 6.55 (d, J = 3.4 Hz, 1H), 4.35 (d, J = 5.2 Hz, 2H), 2.07 (d, J = 12.0 Hz, 1H), 0.87 - 0.75 (m, 4H).
MS(ESI+) m/z 360 (M+H)+
실시예 524: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-N-(2,2,2-트리플루오로에틸)벤즈아미드 (4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(2,2,2-trifluoroethyl)benzamide)의 합성
Figure pat00624
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.60 (s, 1H), 8.02 (s, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.42 (dd, J = 5.4, 17.0 Hz, 3H), 6.53 (s, 1H), 3.54 - 3.47 (m, 2H), 2.02 (dd, J = 7.9, 15.2 Hz, 1H), 0.84 - 0.77 (m, 4H).
MS(ESI+) m/z 403 (M+H)+
실시예 525: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-메틸-N-(2,2,2-트리플루오로에틸)벤즈아미드 (4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methyl-N-(2,2,2-trifluoroethyl)benzamide)의 합성
Figure pat00625
MS(ESI+) m/z 417 (M+H)+
실시예 526: N-( 시아노메틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-메틸벤즈아미드 (N-( cyanomethyl )-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methylbenzamide)의 합성
Figure pat00626
MS(ESI+) m/z 374 (M+H)+
실시예 527: N-( 시아노메틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-N,3-디메틸벤즈아미드 (N-(cyanomethyl)-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-N,3-dimethylbenzamide)의 합성
Figure pat00627
MS(ESI+) m/z 388 (M+H)+
실시예 528: N-( 시아노메틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-2-플루오로벤즈아미드 (N-( cyanomethyl )-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-2-fluorobenzamide)의 합성
Figure pat00628
MS(ESI+) m/z 378 (M+H)+
실시예 529: N-( 시아노메틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-2,6-디플루오로벤즈아미드 (N-(cyanomethyl)-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,6-difluorobenzamide)의 합성
Figure pat00629
MS(ESI+) m/z 396 (M+H)+
실시예 530: N-( 시아노메틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)시클로헥스-3-엔-1-카르복사미드 (N-(cyanomethyl)-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohex-3-ene-1-carboxamide)의 합성
Figure pat00630
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 8.62 (t, J = 5.6 Hz, 1H), 7.83 (s, 1H), 7.31 (dd, J = 3.5, 2.5 Hz, 1H), 6.50 (dd, J = 3.6, 1.8 Hz, 1H), 6.31 (s, 1H), 4.16 (d, J = 5.6 Hz, 2H), 2.40 (s, 2H), 2.00 (d, J = 12.1 Hz, 2H), 1.72 (ddt, J = 17.9, 12.1, 6.3 Hz, 1H), 0.79 (ddt, J = 13.1, 5.1, 3.0 Hz, 4H)
MS(ESI+) m/z 364 (M+H)+
실시예 531: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-N-(2,2,2-트리플루오로에틸)시클로헥스-3-엔-1-카르복사미드 (4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(2,2,2-trifluoroethyl)cyclohex-3-ene-1-carboxamide)의 합성
Figure pat00631
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 8.55 (t, J = 6.4 Hz, 1H), 7.83 (s, 1H), 7.31 (dd, J = 3.5, 2.4 Hz, 1H), 6.49 (dd, J = 3.6, 1.9 Hz, 1H), 6.32 (d, J = 4.0 Hz, 1H), 3.94 (ddt, J = 11.6, 9.1, 4.9 Hz, 2H), 2.62 - 2.54 (m, 2H), 2.39 (d, J = 6.7 Hz, 2H), 2.05 - 1.95 (m, 3H), 1.73 (ddt, J = 17.9, 12.1, 6.3 Hz, 1H), 0.87-0.72 (m, 4H)
MS(ESI+) m/z 407 (M+H)+
실시예 532: N-(2- 시아노에틸 )-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)시클로헥스-3-엔-1-카르복사미드 (N-(2-cyanoethyl)-4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohex-3-ene-1-carboxamide)의 합성
Figure pat00632
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 10.49 (s, 1H), 8.27 (t, J = 5.8 Hz, 1H), 7.83 (s, 1H), 7.38 - 7.27 (m, 1H), 6.50 (dd, J = 3.6, 1.9 Hz, 1H), 6.31 (s, 1H), 2.67 (t, J = 6.5 Hz, 2H), 2.56-2.43 (m, 3H) 2.38 (d, J = 6.0 Hz, 2H), 2.06 - 1.93 (m, 3H), 1.79 - 1.67 (m, 1H), 0.85 (t, J = 6.4 Hz, 1H), 0.79 (ddt, J = 10.1, 5.0, 2.6 Hz, 4H).
MS(ESI+) m/z 378 (M+H)+
실시예 533: N-(4-(4-((N- 메틸술파모일 ) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((N- methylsulfamoyl ) methyl ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00633
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 10.66 (s, 1H), 8.05 (d, J = 4.7 Hz, 1H), 7.73 (d, J = 7.9 Hz, 2H), 7.54 (d, J = 7.9 Hz, 2H), 7.42 (t, J = 3.1 Hz, 1H), 7.04 - 6.94 (m, 1H), 6.54 (dd, J = 3.7, 1.8 Hz, 1H), 4.42 (s, 2H), 2.62 (d, J = 4.7 Hz, 3H), 2.07 - 2.00 (m, 1H), 0.85-0.72 (m, 4H)
MS(ESI+) m/z 385 (M+H)+
실시예 534: N-(4-(4-(( 모르폴리노설포닐 ) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((morpholinosulfonyl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00634
1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 10.66 (s, 1H), 8.06 (s, 1H), 7.75 (d, J = 7.8 Hz, 2H), 7.59 (d, J = 7.8 Hz, 2H), 7.43 (s, 1H), 6.54 (s, 1H), 4.54 (s, 2H), 3.61 (s, 4H), 3.15 (d, J = 5.8 Hz, 4H), 2.05 (s, 1H), 0.86-0.75 (m, 4H).
MS(ESI+) m/z 441 (M+H)+
실시예 535: N-(4-(4-(2-(1,1- 디옥시티오모르폴리노 )-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1,1-dioxidothiomorpholino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00635
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (s, 1H), 8.03 (s, 1H), 7.67 (d, J = 7.8 Hz, 2H), 7.56 (s, 1H), 7.41 (d, J = 6.9 Hz, 2H), 6.54 (s, 1H), 3.94 - 3.88 (m, 4H), 3.16 (d, J = 21.7 Hz, 4H), 2.05 (s, 1H), 0.89-0.76 (m, 4H)
MS(ESI+) m/z 453 (M+H)+
실시예 536: N-(4-(4-(2- 모르폴리노 -2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리 딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-morpholino-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00636
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (s, 1H), 8.03 (s, 1H), 7.67 (d, J = 7.7 Hz, 2H), 7.39 (d, J = 7.5 Hz, 2H), 6.54 (s, 1H), 3.81 (s, 2H), 3.53 (s, 6H), 3.48 (s, 2H), 2.05 (s, 1H), 0.88-0.77 (m, 4H).
MS(ESI+) m/z 405 (M+H)+
실시예 537: N-(4-(4-(2-옥소-2-((2,2,2- 트리플루오로에틸 )아미노)에틸)페닐)-1H피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00637
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.63 (s, 1H), 8.83 (s, 1H), 8.02 (s, 1H), 7.66 (d, J = 7.7 Hz, 2H), 7.59 - 7.54 (m, 1H), 7.42 (t, J = 7.1 Hz, 2H), 6.53 (s, 1H), 4.00 - 3.91 (m, 2H), 3.61 (s, 2H), 2.05 (s, 1H), 0.87 - 0.76 (m, 4H).
MS(ESI+) m/z 417 (M+H)+
실시예 538: N-(4-(4-(2-((1,1- 디옥시테트라히드로티오펜 -3-일)아미노)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-((1,1-dioxidotetrahydrothiophen-3-yl)amino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00638
MS(ESI+) m/z 453 (M+H)+
실시예 539: N-(4-(4-(2-( 메틸아미노 )-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-( methylamino )-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00639
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.03 (d, J = 8.0 Hz, 2H), 7.69 - 7.60 (m, 2H), 7.47 - 7.36 (m, 3H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 3.47 (s, 3H), 2.60 (d, J = 4.6 Hz, 2H), 2.08 - 1.98 (m, 1H), 0.83 - 0.73 (m, 4H).
MS(ESI+) m/z 349 (M+H)+
실시예 540: N-(4-(4-(2-(디메틸아미노)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-( dimethylamino )-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00640
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.71 - 7.62 (m, 2H), 7.43 - 7.35 (m, 3H), 6.54 (dd, J = 3.5, 1.8 Hz, 1H), 3.77 (s, 2H), 3.04 (s, 3H), 2.85 (s, 3H), 2.03 (d, J = 8.1 Hz, 1H), 0.83 - 0.76 (m, 4H).
MS(ESI+) m/z 363 (M+H)+
실시예 541: N-(4-(4-(2-( 에틸아미노 )-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-( ethylamino )-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00641
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.11 (t, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.72 - 7.59 (m, 2H), 7.49 - 7.31 (m, 4H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 3.45 (s, 2H), 3.08 (qd, J = 7.2, 5.4 Hz, 2H), 2.09 - 1.98 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 0.85 - 0.72 (m, 4H).
MS(ESI+) m/z 363 (M+H)+
실시예 542: N-(4-(4-(2-(4-( 메틸술포닐 )피페라진-1-일)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-(methylsulfonyl)piperazin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00642
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.64 (s, 1H), 8.03 (s, 1H), 7.67 (d, J = 8.1 Hz, 2H), 7.46 - 7.36 (m, 3H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 3.84 (s, 2H), 3.66 (s, 4H), 3.09 (d, J = 5.3 Hz, 4H), 2.88 (s, 3H), 2.09 - 1.99 (m, 1H), 0.84 - 0.73 (m, 4H).
MS(ESI+) m/z 482 (M+H)+
실시예 543: N-(4-(4-(2-(4- 아세틸피페라진 -1-일)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-acetylpiperazin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00643
MS(ESI+) m/z 446 (M+H)+
실시예 544: N-(4-(4-(2-( 이소옥사졸 -3- 일아미노 )-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(isoxazol-3-ylamino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00644
1H NMR (400 MHz, Chloroform-d) δ 8.23 (d, J = 1.7 Hz, 1H), 8.01 (s, 1H), 7.70 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 7.8 Hz, 2H), 7.20 (d, J = 3.5 Hz, 1H), 7.01 (s, 1H), 6.58 (s, 1H), 3.75 (s, 2H), 2.19 - 2.10 (m, 1H), 1.97 (d, J = 12.6 Hz, 1H), 0.83 - 0.80 (m, 4H).
MS(ESI+) m/z 402 (M+H)+
실시예 545: N-(4-(4-(2-(1,1- 디옥시티오모르폴리노 )-2- 옥소에틸 )-2- 메틸페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1,1-dioxidothiomorpholino)-2-oxoethyl)-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00645
MS(ESI+) m/z 467 (M+H)+
실시예 546: N-(4-(4-(2-( 아제티딘 -1-일)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-( azetidin -1- yl )-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00646
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.71 - 7.62 (m, 2H), 7.42 - 7.36 (m, 3H), 6.54 (dd, J = 3.5, 1.7 Hz, 1H), 4.21 (t, J = 7.7 Hz, 2H), 3.84 (dt, J = 16.3, 8.0 Hz, 2H), 3.48 (s, 6H), 2.19 (p, J = 7.7 Hz, 1H), 2.01 (dd, J = 14.7, 7.3 Hz, 3H), 0.85 - 0.71 (m, 4H).
MS(ESI+) m/z 375 (M+H)+
실시예 547: N-(4-(4-(2-옥소-2-( 피롤리딘 -1-일)에틸)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- oxo -2-( pyrrolidin -1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00647
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.70 - 7.62 (m, 2H), 7.43 - 7.37 (m, 3H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 3.70 (s, 2H), 3.51 (t, J = 6.8 Hz, 2H), 3.31 (t, J = 6.8 Hz, 2H), 2.07 - 1.97 (m, 1H), 1.89 (p, J = 6.8 Hz, 2H), 1.77 (p, J = 6.8 Hz, 2H), 0.84 - 0.74 (m, 4H).
MS(ESI+) m/z 389 (M+H)+
실시예 548: N-(4-(4-(2-(4- 시아노피페리딘 -1-일)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-cyanopiperidin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00648
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.71 - 7.63 (m, 2H), 7.44 - 7.36 (m, 3H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 3.89 - 3.78 (m, 3H), 3.08 (s, 1H), 2.07 - 1.94 (m, 2H), 1.90 - 1.77 (m, 2H), 1.60 (ddt, J = 12.8, 8.9, 4.7 Hz, 2H), 0.83 - 0.75 (m, 4H).
MS(ESI+) m/z 428 (M+H)+
실시예 549: N-(4-(4-(2-옥소-2-(4- 옥소피페리딘 -1-일)에틸)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-oxo-2-(4-oxopiperidin-1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00649
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.67 (d, J = 7.9 Hz, 2H), 7.46 - 7.37 (m, 3H), 6.54 (dd, J = 3.6, 1.9 Hz, 1H), 3.90 (s, 2H), 3.86 - 3.73 (m, 4H), 2.36 (q, J = 5.5, 4.8 Hz, 2H), 2.06 - 1.96 (m, 2H), 1.15 (d, J = 6.6 Hz, 2H), 0.80 (m, 4H).
MS(ESI+) m/z 417 (M+H)+
실시예 550: N-(4-(4-(2-(4- 메틸피페라진 -1-일)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00650
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.03 (s, 1H), 7.71 - 7.63 (m, 2H), 7.42 - 7.36 (m, 3H), 6.53 (dd, J = 3.5, 1.8 Hz, 1H), 3.79 (s, 2H), 3.55 - 3.44 (m, 4H), 2.24 (q, J = 4.6 Hz, 4H), 2.15 (s, 3H), 2.08 - 1.98 (m, 1H), 0.80 (m, 4H).
MS(ESI+) m/z 418 (M+H)+
실시예 551: N-(4-(4-(2-(4- 에틸피페라진 -1-일)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-ethylpiperazin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00651
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.03 (s, 1H), 7.70 - 7.63 (m, 2H), 7.43 - 7.37 (m, 3H), 6.56 - 6.50 (m, 1H), 3.79 (s, 2H), 3.55 - 3.44 (m, 4H), 2.29 (td, J = 8.4, 7.8, 5.2 Hz, 6H), 2.04 - 1.96 (m, 1H), 0.98 (t, J = 6.8 Hz, 3H), 0.83 - 0.71 (m, 4H).
MS(ESI+) m/z 432 (M+H)+
실시예 552: N-(4-(4-(2-(4- 이소프로필피페라진 -1-일)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-isopropylpiperazin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00652
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.70 - 7.62 (m, 2H), 7.49 - 7.44 (m, 1H), 7.42 - 7.35 (m, 3H), 7.11 (d, J = 7.8 Hz, 1H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 3.79 (s, 2H), 3.55 - 3.43 (m, 4H), 2.63 (d, J = 6.5 Hz, 1H), 2.37 (d, J = 9.1 Hz, 4H), 2.05 - 1.95 (m, 1H), 0.94 (d, J = 6.5 Hz, 6H), 0.81 (qd, J = 9.0, 7.8, 4.5 Hz, 4H).
MS(ESI+) m/z 446 (M+H)+
실시예 553: N-(4-(4-(2-((2- 시아노에틸 )아미노)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-((2-cyanoethyl)amino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00653
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.65 (d, J = 8.1 Hz, 2H), 7.49 - 7.36 (m, 3H), 6.53 (dd, J = 3.5, 1.8 Hz, 1H), 3.53 (s, 2H), 3.31 (m, 2H), 2.66 (m, 2H), 2.07 - 1.96 (m, 1H), 0.82 (m, 4H).
MS(ESI+) m/z 388 (M+H)+
실시예 554: tert - 부틸4 -(2-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아세틸)피페라진-1-카르복실레이트 ( tert - butyl 4-(2-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)acetyl)piperazine-1-carboxylate)의 합성
Figure pat00654
1H NMR (400 MHz, DMSO-d6) δ 11.54 (d, J = 2.6 Hz, 1H), 10.63 (s, 1H), 8.03 (s, 1H), 7.72 - 7.63 (m, 2H), 7.44 - 7.35 (m, 3H), 6.54 (dd, J = 3.6, 1.9 Hz, 1H), 3.82 (s, 2H), 3.58 - 3.43 (m, 4H), 3.32 - 3.24 (m, 4H), 2.07 - 1.94 (m, 1H), 1.40 (s, 9H), 0.87 - 0.74 (m, 4H).
MS(ESI+) m/z 504 (M+H)+
실시예 555: tert - 부틸3 -(2-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아세트아미드)피페리딘-1-카르복실레이트 ( tert - butyl 3-(2-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)acetamido)piperidine-1-carboxylate)의 합성
Figure pat00655
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.63 (s, 1H), 8.11 (d, J = 7.5 Hz, 1H), 8.02 (s, 1H), 7.65 (d, J = 8.1 Hz, 2H), 7.46 - 7.37 (m, 3H), 6.53 (dd, J = 3.4, 1.8 Hz, 1H), 3.64 - 3.53 (m, 2H), 3.50 (s, 3H), 2.00 (dt, J = 14.5, 6.7 Hz, 2H), 1.85 - 1.76 (m, 1H), 1.73 - 1.61 (m, 1H), 1.37 (s, 13H), 1.23 (s, 5H), 0.88 - 0.72 (m, 6H).
MS(ESI+) m/z 518 (M+H)+
실시예 556: N-(4-(4-(2-((1- 메틸 -1H- 피라졸 -3-일)아미노)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-((1-methyl-1H-pyrazol-3-yl)amino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00656
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.68 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.67 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 2.2 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.40 (dd, J = 3.5, 2.4 Hz, 1H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 6.42 (d, J = 2.2 Hz, 1H), 3.73 (s, 3H), 3.68 (s, 2H), 2.02 (m, 1H), 0.84 - 0.73 (m, 4H).
MS(ESI+) m/z 415 (M+H)+
실시예 557: N-(4-(4-(2-옥소-2-(피페리딘-1-일)에틸)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- oxo -2-( piperidin -1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00657
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.60 (d, J = 3.9 Hz, 1H), 8.03 (d, J = 3.2 Hz, 1H), 7.67 (d, J = 6.8 Hz, 2H), 7.40 (s, 3H), 6.53 (s, 1H), 3.78 (s, 2H), 3.60 (s, 2H), 3.46 (s, 2H), 2.04 (s, 1H), 1.75 (d, J = 4.4 Hz, 2H), 1.55 (s, 2H), 1.41 (s, 2H), 0.82-0.75 (m, 4H).
MS(ESI+) m/z 403 (M+H)+
실시예 558: N-(4-(4-(2-옥소-2-(피페라진-1-일)에틸)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- oxo -2-( piperazin -1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00658
1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.69 (dd, J = 8.2, 3.9 Hz, 2H), 7.36 - 7.29 (m, 2H), 7.20 (q, J = 3.1 Hz, 1H), 6.57 (q, J = 3.1 Hz, 1H), 5.34 - 5.24 (m, 2H), 3.84 - 3.73 (m, 2H), 3.63 (d, J = 5.2 Hz, 2H), 3.45 (d, J = 5.3 Hz, 2H), 2.81 (s, 2H), 2.67 (d, J = 5.3 Hz, 2H), 1.65 (s, 1H), 1.07 (q, J = 3.9 Hz, 2H), 0.85 (m, 2H).
MS(ESI+) m/z 404 (M+H)+
실시예 559: N-(4-(4-(2-(1,1- 디옥시티오모르폴리노 )-2- 옥소에틸 )-3- 플루오로페닐 )-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1,1-dioxidothiomorpholino)-2-oxoethyl)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00659
MS(ESI+) m/z 471 (M+H)+
실시예 560: N-(4-(4-(2-옥소-2- 티오모르폴리노에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-oxo-2-thiomorpholinoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00660
MS(ESI+) m/z 421 (M+H)+
실시예 561: N-(4-(4-(2-(4,4- 디플루오로피페리딘 -1-일)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4,4-difluoropiperidin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00661
MS(ESI+) m/z 439 (M+H)+
실시예 562: N-(4-(4-(2-옥소-2-(4-( 트리플루오로메틸술포닐 )피페라진-1-일)에틸)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-oxo-2-(4-(trifluoromethylsulfonyl)piperazin-1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide) 의 합성
Figure pat00662
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 8.01 (s, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.43 - 7.31 (m, 3H), 6.52 (dd, J = 3.5, 1.9 Hz, 1H), 4.33 (d, J = 4.3 Hz, 1H), 3.77 (s, 2H), 2.60 (dd, J = 12.1, 5.3 Hz, 8H), 2.00 (m, 1H), 0.84-0.76 (m, 4H).
MS(ESI+) m/z 537 (M+H)+
실시예 563: N-(4-(4-(2-(4-( 에틸술포닐 )피페라진-1-일)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-(ethylsulfonyl)piperazin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide) 의 합성
Figure pat00663
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 1H), 8.03 (s, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 7.6 Hz, 3H), 6.53 (d, J = 3.4 Hz, 1H), 3.84 (s, 2H), 3.64 3.57 (m, 2H), 3.20 - 3.10 (m, 4H), 3.11 - 2.99 (m, 4H), 2.07 - 1.95 (m, 1H), 1.24 - 1.14 (m, 3H), 0.82 (dd, J = 16.1, 11.1 Hz, 4H).
MS(ESI+) m/z 497 (M+H)+
실시예 564: N-(4-(4-(2-옥소-2-(4-( 프로필술포닐 )피페라진-1-일)에틸)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-oxo-2-(4-(propylsulfonyl)piperazin-1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide) 의 합성
Figure pat00664
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.61 (s, 1H), 8.03 (s, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.40 (dd, J = 6.2, 2.1 Hz, 3H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 3.84 (s, 2H), 3.68 - 3.54 (m, 4H), 3.14 (m, 4H), 3.08-2.99 (m, 2H), 2.04 - 1.97 (m, 1H), 1.75 - 1.60 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H), 0.85 - 0.74 (m, 4H).
MS(ESI+) m/z 511 (M+H)+
실시예 565: 에틸 4-(2-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐)아세틸)피페라진-1-카르복실레이트 ( ethyl 4-(2-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)acetyl)piperazine-1-carboxylate) 의 합성
Figure pat00665
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 1H), 8.03 (s, 1H), 7.66 (d, J = 7.8 Hz, 2H), 7.45 - 7.35 (m, 3H), 6.54 (dd, J = 3.5, 1.8 Hz, 1H), 4.05 (q, J = 7.0 Hz, 2H), 3.83 (s, 2H), 3.58 - 3.44 (m, 4H), 2.07 - 1.96 (m, 1H), 1.18 (t, J = 6.9 Hz, 3H), 0.85 - 0.75 (m, 4H).
MS(ESI+) m/z 477 (M+H)+
실시예 566: N-(4-(4-(2-(2-옥소-2-(4-(N-(2,2,2- 트리플루오로에틸 ) 설파모일 )피페라진-1-일)에틸)페닐)-1H-피롤로[2,3 b]피리딘-6-일) 시클로프로판카르복사미드 (N-(4-(4-(2- oxo -2-(4-(N-(2,2,2- trifluoroethyl ) sulfamoyl ) piperazin -1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00666
MS(ESI+) m/z 565 (M+H)+
실시예 567: N-(4-(4-(2-(3- 시아노피롤리딘 -1-일)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(3-cyanopyrrolidin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00667
MS(ESI+) m/z 414 (M+H)+
실시예 568: N-(4-(4-(2-(3- 시아노아제티딘 -1-일)-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00668
MS(ESI+) m/z 400 (M+H)+
실시예 569: N-(4-(4-(2-(3,3- 디플루오로피롤리딘 -1-일)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(3,3-difluoropyrrolidin-1-yl)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00669
1H NMR (400 MHz, DMSO-d6) δ 11.52 (d, J = 4.0 Hz, 1H), 10.60 (d, J = 3.6 Hz, 1H), 8.02 (d, J = 3.4 Hz, 1H), 7.66 (d, J = 6.0 Hz, 2H), 7.40 (s, 3H), 6.54 (s, 1H), 4.11 - 3.98 (m, 1H), 3.78 (dd, J = 25.2, 10.0 Hz, 5H), 3.55 (s, 2H), 2.03 (s, 1H), 0.82-0.75 (s, 4H).
MS(ESI+) m/z 425 (M+H)+
실시예 570: N-(4-(4-(2-옥소-2-(4-( 트리플루오로메틸 )피페리딘-1-일)에틸)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-oxo-2-(4-(trifluoromethyl)piperidin-1-yl)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00670
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (d, J = 2.9 Hz, 1H), 8.02 (d, J = 2.8 Hz, 1H), 7.66 (t, J = 6.1 Hz, 2H), 7.40 (d, J = 4.1 Hz, 3H), 6.52 (s, 1H), 4.56 - 4.47 (m, 1H), 4.09 (d, J = 13.9 Hz, 1H), 3.85 - 3.79 (m, 2H), 3.06 (t, J = 13.5 Hz, 1H), 2.58 (d, J = 12.3 Hz, 2H), 2.03 (s, 1H), 1.87 - 1.73 (m, 2H), 1.25 (d, J = 13.1 Hz, 2H), 0.82-0.75 (m, 4H).
MS(ESI+) m/z 471 (M+H)+
실시예 571: N-(4-(4-(2-(1,1- 디옥시티오모르폴리노 )-1,1- 디플루오로 -2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1,1-dioxidothiomorpholino)-1,1-difluoro-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00671
MS(ESI+) m/z 489 (M+H)+
실시예 572: N-(4-(4-(1,1- 디플루오로 -2- 모르폴리노 -2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(1,1-difluoro-2-morpholino-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00672
MS(ESI+) m/z 441 (M+H)+
실시예 573: N-(4-(4-(2-(( 시아노메틸 )( 메틸 )아미노)-2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-((cyanomethyl)(methyl)amino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00673
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.67 (s, 1H), 8.00 (s, 1H), 7.68 (d, J = 8.1 Hz, 2H), 7.43 - 7.37 (m, 3H), 6.55 (dd, J = 3.6, 1.9 Hz, 1H), 4.43 (s, 2H), 3.88 (s, 3H), 3.15 (s, 3H), 2.06 - 2.02 (m, 1H), 0.85 - 0.80 (m, 4H).
MS(ESI+) m/z 388 (M+H)+
실시예 574: N-(4-(4-(2-(1- 옥소티오모르폴린 )-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1-oxidothiomorpholino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00674
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.65 (s, 1H), 8.02 (s, 1H), 7.68 (d, J = 7.9 Hz, 2H), 7.44 - 7.38 (m, 3H), 6.55 (dd, J = 3.5, 1.9 Hz, 1H), 3.87 (d, J = 11.3 Hz, 2H), 3.62 (dd, J = 6.6, 3.9 Hz, 4H), 3.13 (tt, J = 7.4, 3.7 Hz, 4H), 2.04 (d, J = 6.5 Hz, 1H), 0.85 - 0.79 (m, 4H).
MS(ESI+) m/z 437 (M+H)+
실시예 575: N-(4-(4-(2-(4- 시아노피페리딘 -1-일)-1,1- 디플루오로 -2- 옥소에틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(4-cyanopiperidin-1-yl)-1,1-difluoro-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00675
MS(ESI+) m/z 464 (M+H)+
실시예 576: N-(4-(4-(2-(3- 시아노모르폴리노 )-2- 옥소에틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(3-cyanomorpholino)-2-oxoethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00676
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (s, 1H), 8.04 (s, 1H), 7.71 - 7.66 (m, 2H), 7.45 - 7.36 (m, 3H), 6.54 (dd, J = 3.5, 1.8 Hz, 1H), 4.03 (d, J = 12.3 Hz, 2H), 3.94 - 3.90 (m, 2H), 3.62 - 3.56 (m, 1H), 3.46 (s, 1H), 2.04 (d, J = 9.1 Hz, 1H), 1.28 - 1.23 (m, 4H), 0.86 - 0.79 (m, 4H).
MS(ESI+) m/z 430 (M+H)+
실시예 577: N-(4-(4-(1-(1,1- 디옥시도티오모르폴린 -4-카르보닐) 시클로프로필 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(1-(1,1-dioxidothiomorpholine-4-carbonyl)cyclopropyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00677
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.62 (s, 1H), 8.03 (s, 1H), 7.70 (dd, J = 7.6, 5.9 Hz, 3H), 7.42 - 7.40 (m, 1H), 7.34 (d, J = 8.3 Hz, 2H), 6.53 (dd, J = 3.5, 1.9 Hz, 1H), 3.39 (s, 2H), 2.92 (s, 2H), 2.04 - 2.00 (m, 1H), 1.51 - 1.47 (m, 2H), 1.26 (dd, J = 9.2, 4.0 Hz, 4H), 0.84 - 0.77 (m, 4H).
MS(ESI+) m/z 479 (M+H)+
실시예 578: N-(4-(1-(2-(1,1-디옥시도티오모르폴리노)-2-옥소에틸)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(2-(1,1-dioxidothiomorpholino)-2-oxoethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00678
1H NMR (400 MHz, Chloroform-d) δ 11.40 (s, 1H), 10.51 (s, 1H), 7.86 (s, 1H), 7.37 - 7.28 (m, 1H), 6.60 - 6.52 (m, 1H), 6.33 (s, 1H), 3.99 (s, 2H), 3.89 (s, 2H), 3.39 (s, 2H), 3.19 (d, J = 37.2 Hz, 5H), 2.74 (t, J = 5.6 Hz, 2H), 2.00 (d, J = 11.4 Hz, 1H), 0.88 - 0.75 (m, 4H).
MS(ESI+) m/z 458 (M+H)+
실시예 579: N-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)벤질)모르폴린-4-카르복사미드 (N-(4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)benzyl)morpholine-4-carboxamide)의 합성
Figure pat00679
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (s, 1H), 8.01 (s, 1H), 7.66 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.4 Hz, 3H), 7.21 (s, 1H), 6.53 (s, 1H), 4.32 (s, 2H), 2.42-2.83 (m, 4H), 1.98 - 2.12 (m, 1H), 1.21-1.41 (m, 4H), 0.72-0.95 (m, 4H).
MS(ESI+) m/z 420 (M+H)+
실시예 580: N-(4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)벤질)티오모르폴린-4-카르복스아미드1,1-디옥시드 (N-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)benzyl)thiomorpholine-4-carboxamide 1,1- dioxide )의 합성
Figure pat00680
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 5.1 Hz, 1H), 7.44 (d, J = 7.9 Hz, 2H), 7.42 - 7.38 (m, 1H), 6.58 - 6.49 (m, 1H), 4.34 (d, J = 5.8 Hz, 2H), 3.82 (d, J = 5.5 Hz, 4H), 3.16 - 3.06 (m, 4H), 2.04 (s, 1H), 0.80 (dd, J = 4.0, 12.0 Hz, 4H).
MS(ESI+) m/z 468 (M+H)+
실시예 581: N-(4-(4-((3-(2,2,2- 트리플루오로에틸 ) 우레이도 ) 메틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-((3-(2,2,2-trifluoroethyl)ureido)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00681
1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.63 (s, 1H), 8.02 (s, 1H), 7.67 (d, J = 7.8 Hz, 2H), 7.45 - 7.34 (m, 3H), 6.75 (t, J = 6.0 Hz, 1H), 6.66 (t, J = 6.6 Hz, 1H), 6.55 - 6.47 (m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 3.93 - 3.78 (m, 2H), 2.04 (s, 1H), 0.81 (dt, J = 5.3, 10.2 Hz, 4H).
MS(ESI+) m/z 432 (M+H)+
실시예 582: N-(4-(4-(((3,4- 디플루오로페닐 ) 술폰아미도 ) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(((3,4-difluorophenyl)sulfonamido)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00682
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.61 (s, 1H), 8.24 (br s, 1H), 7.99 (s, 1H), 7.79 (d, J = 2.3 Hz, 1H), 7.69 - 7.58 (m, 4H), 7.44 - 7.33 (m, 3H), 6.52 - 6.43 (m, 1H), 4.13 (s, 2H), 2.04 (d, J = 5.7 Hz, 1H), 0.88 - 0.74 (m, 4H).
MS(ESI+) m/z 483 (M+H)+
실시예 583: N-(4-(4-( 프로필술포닐아미도메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( propylsulfonamidomethyl ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00683
1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 10.64 (s, 1H), 8.05 (d, J = 15.8 Hz, 1H), 7.79 - 7.65 (m, 3H), 7.52 (d, J = 8.1 Hz, 2H), 7.41 (s, 1H), 6.52 (s, 1H), 4.22 (d, J = 4.7 Hz, 2H), 3.02 - 2.91 (m, 2H), 2.05 (s, 1H), 1.72 - 1.59 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H), 0.81 (d, J = 6.7 Hz, 4H).
MS(ESI+) m/z 413 (M+H)+
실시예 584: N-(4-(4-((1,1- 디옥시도티오모르폴리노 ) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00684
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (s, 1H), 8.03 (s, 1H), 7.70 (d, J = 7.9 Hz, 2H), 7.51 (d, J = 7.9 Hz, 2H), 7.40 (t, J = 3.0 Hz, 1H), 6.63 - 6.39 (m, 1H), 3.75 (s, 2H), 3.13 (t, J = 5.1 Hz, 5H), 3.01 - 2.82 (m, 4H), 2.05 (t, J = 11.7 Hz, 1H), 0.81 (dt, J = 5.7, 10.4 Hz, 4H).
MS(ESI+) m/z 425 (M+H)+
실시예 585: N-(4-(4-(4- 옥소피페리딘 -1-일) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4- oxopiperidin -1-yl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00685
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (s, 1H), 8.04 (s, 1H), 7.78 - 7.66 (m, 2H), 7.53 (d, J = 7.9 Hz, 2H), 7.40 (t, J = 3.0 Hz, 1H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 3.70 (s, 2H), 2.74 (t, J = 6.0 Hz, 4H), 2.38 (t, J = 6.0 Hz, 4H), 2.04 (d, J = 8.8 Hz, 1H), 0.91 - 0.75 (m, 4H).
MS(ESI+) m/z 389 (M+H)+
실시예 586: N-(4-(4-((3- 시아노아제티딘 -1-일) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3- cyanoazetidin -1-yl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00686
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.61 (s, 1H), 8.02 (s, 1H), 7.75 - 7.64 (m, 2H), 7.48 - 7.41 (m, 2H), 7.40 (dd, J = 2.4, 3.5 Hz, 1H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 3.66 (s, 2H), 3.55 - 3.45 (m, 4H), 2.04 (d, J = 7.0 Hz, 1H), 0.81 (ddd, J = 2.6, 6.4, 11.7 Hz, 4H).
MS(ESI+) m/z 372 (M+H)+
실시예 587: N-(4-(4-((4-( 메틸술포닐 )피페라진-1-일) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00687
MS(ESI+) m/z 454 (M+H)+
실시예 588: N-(4-(4-((1,1- 디옥시도티오모르폴리노 ) 메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)-2-메틸시클로프로판-1-카르복사미드 (N-(4-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylcyclopropane-1-carboxamide)의 합성
Figure pat00688
MS(ESI+) m/z 439 (M+H)+
실시예 589: N-(4-(4-(1-(1,1- 디옥시도티오모르폴리노 )에틸)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(1-(1,1-dioxidothiomorpholino)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00689
1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 10.62 (s, 1H), 8.03 (s, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 7.9 Hz, 2H), 7.45 - 7.36 (m, 1H), 6.55 (s, 1H), 3.99 (s, 1H), 3.10 (s, 4H), 2.93 (s, 4H), 2.05 (s, 1H), 1.40 (d, J = 6.7 Hz, 3H), 0.83 - 0.77 (m, 4H).
MS(ESI+) m/z 439 (M+H)+
실시예 590: N-(4-(3,5- 디플루오로 -4-( 모르폴리노메틸 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(3,5-difluoro-4-(morpholinomethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00690
1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 10.72 (s, 1H), 8.05 (s, 1H), 7.47 (d, J = 2.8 Hz, 1H), 7.44 - 7.35 (m, 2H), 6.63 - 6.55 (m, 1H), 3.63 (s, 2H), 3.56 (t, J = 4.5 Hz, 4H), 2.45 - 2.42 (m, 2H), 2.04 (s, 1H), 0.86 - 0.78 (m, 4H).
MS(ESI+) m/z 413 (M+H)+
실시예 591: N-(4-(4-(2-(1,1- 디옥시도티오모르폴리노 )에틸)페닐)-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4-(2-(1,1-dioxidothiomorpholino)ethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00691
1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.60 (s, 1H), 8.01 (s, 1H), 7.71 - 7.59 (m, 2H), 7.50 - 7.34 (m, 3H), 6.52 (dd, J = 3.5, 1.7 Hz, 1H), 3.10 (d, J = 5.6 Hz, 4H), 3.05 - 2.93 (m, 4H), 2.86 - 2.73 (m, 4H), 2.03 (m, 1H), 0.90 - 0.74 (m, 4H).
MS(ESI+) m/z 439 (M+H)+
실시예 592: N-(6-(4-((1,1- 디옥시도티오모르폴리노 ) 메틸 )페닐)-9H- 푸린 -2-일)시클로프로판카르복사미드 (N-(6-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-9H-purin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00692
1H NMR (400 MHz, DMSO-d6) δ 10.79 (s, 1H), 8.88 - 8.79 (m, 2H), 8.51 (s, 1H), 7.69 - 7.58 (m, 2H), 3.62 - 3.55 (m, 2H), 3.29 (d, J = 21.0 Hz, 8H), 2.18 (dd, J = 8.6, 3.7 Hz, 1H), 0.84 (ddt, J = 10.7, 4.9, 2.9 Hz, 4H).
MS(ESI+) m/z 427 (M+H)+
실시예 593: N-(7-(4-((5- 메틸 -2H- 테트라졸 -2-일) 메틸 )페닐)-3H- 이미다조[4,5-b]피리딘 -5-일)시클로프로판카르복사미드 (N-(7-(4-((5-methyl-2H-tetrazol-2-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)cyclopropanecarboxamide)의 합성
Figure pat00693
MS(ESI+) m/z 375 (M+H)+
실시예 594: N-(7-(4-((5- 메틸 -1H- 테트라졸 -1-일) 메틸 )페닐)-3H- 이미다조[4,5-b]피리딘 -5-일)시클로프로판카르복사미드 (N-(7-(4-((5-methyl-1H-tetrazol-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)cyclopropanecarboxamide)의 합성
Figure pat00694
MS(ESI+) m/z 375 (M+H)+
실시예 595: N-(4-(4-(((1,1- 디옥시도테트라히드로티오펜 -3-일)아미노) 메틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1,1-dioxidotetrahydrothiophen-3-yl)amino)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00695
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 1H), 8.02 (s, 1H), 7.74 - 7.65 (m, 2H), 7.51 (d, J = 7.9 Hz, 2H), 7.45 - 7.38 (m, 1H), 6.58 - 6.46 (m, 1H), 3.80 (s, 2H), 3.48 (s, 1H), 3.28 - 3.19 (m, 1H), 3.05 (dt, J = 7.6, 12.6 Hz, 1H), 2.94 (dd, J = 6.5, 13.1 Hz, 1H), 2.70 (d, J = 23.9 Hz, 2H), 2.30 - 2.23 (m, 1H), 2.04 (dd, J = 7.2, 13.5 Hz, 2H), 0.88 - 0.78 (m, 4H)
MS(ESI+) m/z 425 (M+H)+
실시예 596: N-(4-(4-(((1,1- 디옥시도테트라히드로 -2H- 티오피란 -4-일)아미노)메틸)페닐)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)amino)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00696
1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.61 (s, 1H), 8.02 (s, 1H), 7.76 - 7.35 (m, 9H), 6.65 - 6.47 (m, 1H), 3.78 (s, 1H), 3.09 (d, J = 53.8 Hz, 4H), 2.01 (d, J = 52.3 Hz, 5H), 0.89 - 0.75 (m, 4H).
MS(ESI+) m/z 439 (M+H)+
실시예 597: N-(6-(4-(((4- 플루오로페닐 )아미노) 메틸 )페닐)-9H- 푸린 -2-일) 시클로프로판카르복사미드 (N-(6-(4-(((4- fluorophenyl ) amino ) methyl ) phenyl )-9H-purin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00697
1H NMR (400 MHz, DMSO-d6) δ 10.67 (s, 1H), 8.76 (d, J = 7.9 Hz, 2H), 8.42 (s, 1H), 7.55 (d, J = 8.1 Hz, 2H), 6.89 (t, J = 8.7 Hz, 2H), 6.58 (dd, J = 8.8, 4.5 Hz, 2H), 6.24 (t, J = 6.1 Hz, 1H), 4.33 (d, J = 6.1 Hz, 2H), 2.20 (s, 1H), 0.91 - 0.79 (m, 4H).
MS(ESI+) m/z 403 (M+H)+
실시예 598: N-(6-(4-(((3- 플루오로페닐 )아미노) 메틸 )페닐)-9H- 푸린 -2-일) 시클로프로판카르복사미드 (N-(6-(4-(((3- fluorophenyl ) amino ) methyl ) phenyl )-9H-purin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00698
1H NMR (400 MHz, DMSO-d6) δ 10.73 (s, 1H), 8.72 (d, J = 37.7 Hz, 2H), 8.46 (s, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.05 (q, J = 7.8 Hz, 2H), 6.65 (q, J = 9.8, 8.1 Hz, 1H), 6.44 (d, J = 8.5 Hz, 1H), 6.41 - 6.26 (m, 2H), 4.37 (d, J = 6.1 Hz, 2H), 2.19 (s, 1H), 0.86 - 0.69 (m, 4H).
MS(ESI+) m/z 403 (M+H)+
실시예 599: N-(4-(1-(1-(( 트리플루오로메틸 )술포닐) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00699
단계1) tert-부틸 3-(4-(6-(시클로프로판카르복사미도)-1-토실-1H-피롤로[2,3-b]피리딘-4-일)-1H-피라졸-1-일)아제티딘-1-카르복실레이트의 합성
Figure pat00700
합성된 N-(4-클로로-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 2.5g (6.44 mmol)을 DMF/H2O = 2:1 용액 (50 mL)에 용해시키고, 4 tert-부틸 3-(4-(4,4,5,5-테트라메틸-1,3,2-디옥사보롤란-2-일)-1H-피라졸-1-일) 아제티딘-1-카르복실레이트 2.5g (7.1 mmol), Pd(dppf)Cl2 0.8g (0.97 mmol), K3PO4 1.6 g(7.7 mmol)을 넣고 80 ~ 90 oC 에서 2시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 물과 묽은 염산 첨가 후, pH 4 ~ 5에서 에틸아세테이트로 추출하였다. 추출한 용액을 무수 황산마그네슘으로 건조하고, 감압농축하여 잔여물을 수득하였다. 잔여물을 실리카겔 컬럼크로마토그래피(n-헥산 / 에틸아세테이트 = 1:1)에서 분리하여 tert-부틸 3-(4-(6-(시클로프로판 카르복사미도)-1-토실-1H-피롤로[2,3-b]피리딘-4-일)-1H-피라졸-1-일)아제티딘-1-카르복실레이트 을 주 생성물로 하는 혼합물을 수득하였다.
MS(ESI+) m/z 577 (M+H)+
단계2) N-(4-(1-(아제티딘-3-일)-1H-피라졸-4-일)-1-토실일-1H-피롤로[2,3-b] 피리딘 -6-일)시클로프로판카르복사미드의 합성
Figure pat00701
상기 화합물 tert-부틸 3-(4-(6-(시클로프로판 카르복사미도)-1-토실-1H-피롤로[2,3-b]피리딘-4-일)-1H-피라졸-1-일)아제티딘-1-카르복실레이트 5 g을 디클로로메탄 (50 mL) 에 용해시키고 TFA (5 mL) 를 넣고 실온에서 2시간 동안 교반하였다. 상기 화합물은 별도의 분리 과정 없이 다음 단계를 진행하였다.
MS(ESI+) m/z 477 (M+H)+
단계3) N-(1-토실-4-(1-(1-((트리플루오로메틸)술포닐)아제티딘-3-일)-1H-피라졸-4-일)-1H-피롤로[2,3-b]-시클로프로판카르복사미드의 합성
Figure pat00702
합성된 N-(4-(1-(아제티딘-3-일)-1H-피라졸-4-일)-1-토실일-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (2 g)을 디클로로메탄 (20 mL)에 용해시키고 Et3N (2당량, 1.17 mL)를 넣고 교반하였다. 0 oC 에서 트리플루오로 메탄술포닐클로라이드 (1.5 당량, 1.06 g) 넣은 후, 실온에서 2시간동안 교반하여 화합물 N-(1-토실-4-(1-(1-((트리플루오로메틸)술포닐)아제티딘-3-일)-1H-피라졸-4-일)-1H-피롤로[2,3-b]-시클로프로판카르복사미드 1.6 g (41%, 3단계 누적수율)을 수득하였다.
MS(ESI+) m/z 609 (M+H)+
단계4) N-(4-(1-(1-(1-트리플루오로메틸)술포닐)아제티딘-3-일)-1H-피라졸-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드의 합성
Figure pat00703
합성된 N-(1-토실-4-(1-(1-((트리플루오로메틸)술포닐)아제티딘-3-일)-1H-피라졸-4-일)-1H-피롤로[2,3-b]-시클로프로판카르복사미드를 MeOH / THF (2:1) 50 mL에 용해시키고, 2N 수산화나트륨 수용액을 10 mL 첨가하여, 30 ~ 40 oC에서 4 시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 묽은 염산 수용액을 첨가하여 pH 중성에서 디클로로메탄으로 추출하였다. 추출한 용액은 무수황산마그네슘으로 건조하고, 감압농축하여 잔여물을 수득하였다. 잔여물은 prep. TLC (DCM : MeOH = 30 :1) 방법을 통해 목적 화합물 실시예 599, N-(4-(1-(1-(1-트리플루오로메틸)술포닐)아제티딘-3-일)-1H-피라졸-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.53 (s, 1H), 8.55 (d, J = 9.1 Hz, 1H), 8.20 (s, 1H), 8.07 (s, 1H), 7.47 - 7.35 (m, 1H), 6.82 - 6.70 (m, 1H), 5.68 - 5.55 (m, 1H), 4.71 (dt, J = 7.2, 15.1 Hz, 4H), 2.06 (d, J = 18.0 Hz, 1H), 0.88 - 0.76 (m, 4H).
MS(ESI+) m/z 455 (M+H)+
실시예 600 내지 611
이하, 실시예 600 내지 실시예 611에서는, 실시예 599와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 600: N-(4-(1-( 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-( azetidin -3- yl )-1H- pyrazol -4- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00704
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.51 (s, 1H), 8.48 (s, 1H), 8.06 (s, 2H), 7.37 (s, 1H), 6.73 (s, 1H), 5.32 (s, 1H), 4.04 (s, 2H), 3.83 (d, J = 10.2 Hz, 2H), 2.00 (s, 3H), 1.47 (s, 2H), 0.84 (s, 4H).
MS(ESI+) m/z 323 (M+H)+
실시예 601: N-(4-(1-(1-( 에틸술포닐 ) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(ethylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00705
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.52 (s, 1H), 8.50 (s, 1H), 8.14 (s, 1H), 8.06 (s, 1H), 7.38 (s, 1H), 6.73 (d, J = 3.5 Hz, 1H), 5.41 (p, J = 7.1 Hz, 1H), 4.39 (dd, J = 6.4, 8.6 Hz, 2H), 4.28 (t, J = 8.2 Hz, 2H), 3.25 (q, J = 7.4 Hz, 2H), 2.07 - 1.99 (m, 1H), 1.28 (t, J = 7.3 Hz, 3H), 0.81 (dt, J = 3.3, 15.8 Hz, 4H).
MS(ESI+) m/z 415 (M+H)+
실시예 602: N-(4-(1-(1-( 부틸술포닐 ) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(butylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00706
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.53 (d, J = 6.6 Hz, 1H), 8.50 (s, 1H), 8.10 (d, J = 29.3 Hz, 2H), 7.38 (s, 1H), 6.80 - 6.66 (m, 1H), 5.41 (s, 1H), 4.34 (dq, J = 8.8, 9.7, 40.3 Hz, 4H), 3.27 - 3.19 (m, 2H), 2.04 (s, 1H), 1.71 (d, J = 10.7 Hz, 2H), 1.52 - 1.39 (m, 2H), 1.03 - 0.89 (m, 4H), 0.82 (s, 4H).
MS(ESI+) m/z 443 (M+H)+
실시예 603: N-(4-(1-(1-( 메틸술포닐 ) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(methylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00707
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.53 (s, 1H), 8.52 (s, 1H), 8.10 (d, J = 31.4 Hz, 2H), 7.38 (s, 1H), 6.74 (s, 1H), 5.50 - 5.31 (m, 1H), 4.33 (dd, J = 8.8, 16.6 Hz, 4H), 3.15 (p, J = 6.0 Hz, 3H), 2.03 (s, 1H), 0.83 (d, J = 6.3 Hz, 4H).
MS(ESI+) m/z 401 (M+H)+
실시예 604: N-(4-(1-(1-( 페닐술포닐 ) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(phenylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00708
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.51 (s, 1H), 8.21 (s, 1H), 8.03 - 7.86 (m, 4H), 7.76 (q, J = 8.2, 14.4 Hz, 3H), 7.36 (s, 1H), 6.62 (s, 1H), 5.24 (s, 1H), 4.18 (dt, J = 9.0, 38.6 Hz, 4H), 2.03 (s, 1H), 0.88 - 0.73 (m, 4H).
MS(ESI+) m/z 463 (M+H)+
실시예 605: N-(4-(1-( 1,(3,4-디플루오로페닐)술포닐 ) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H-피롤로[2,3-b]피리딘-6-시클로프로판카르복사미드 (N-(4-(1-(1-((3,4-difluorophenyl)sulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00709
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.51 (s, 1H), 8.31 (s, 1H), 7.98 (d, J = 21.8 Hz, 2H), 7.75 (d, J = 12.9 Hz, 2H), 7.48 (s, 1H), 7.36 (s, 1H), 6.64 (s, 1H), 5.23 (s, 1H), 4.19 (d, J = 24.7 Hz, 4H), 3.96 (s, 3H), 2.02 (s, 1H), 0.80 (d, J = 15.3 Hz, 4H).
MS(ESI+) m/z 499 (M+H)+
실시예 606: N-(4-(1-(1-( 시클로헥실술포닐 ) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(cyclohexylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00710
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.52 (s, 1H), 8.49 (s, 1H), 8.11 (d, J = 31.0 Hz, 2H), 7.44 - 7.30 (m, 1H), 6.73 (s, 1H), 5.40 (d, J = 9.8 Hz, 1H), 4.44 - 4.15 (m, 4H), 3.11 (s, 1H), 2.08 (d, J = 12.9 Hz, 3H), 1.80 (d, J = 11.5 Hz, 2H), 1.64 (s, 1H), 1.27 (dd, J = 35.0, 51.6 Hz, 7H), 0.81 (d, J = 16.2 Hz, 4H).
MS(ESI+) m/z 469 (M+H)+
실시예 607: N-(4-(1-(1-( 메틸술포닐 )피페리딘-4-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00711
1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.50 (s, 1H), 8.43 (s, 1H), 8.02 (d, J = 16.4 Hz, 2H), 7.36 (s, 1H), 6.75 (s, 1H), 4.44 (s, 1H), 3.70 (d, J = 11.9 Hz, 2H), 2.95 (d, J = 6.9 Hz, 5H), 2.27 - 1.98 (m, 6H), 0.86 - 0.75 (m, 4H).
MS(ESI+) m/z 429 (M+H)+
실시예 608: N-(4-(1-(1-( 에틸술포닐 )피페리딘-4-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(ethylsulfonyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00712
1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.49 (s, 1H), 8.42 (s, 1H), 8.02 (d, J = 16.8 Hz, 2H), 7.42 - 7.32 (m, 1H), 6.75 (d, J = 3.2 Hz, 1H), 4.44 (d, J = 12.9 Hz, 1H), 3.74 (d, J = 12.2 Hz, 2H), 3.07 (ddd, J = 8.6, 13.4, 31.8 Hz, 4H), 2.20 - 1.96 (m, 5H), 1.24 (t, J = 7.3 Hz, 3H), 0.80 (d, J = 17.7 Hz, 4H).
MS(ESI+) m/z 443 (M+H)+
실시예 609: N-(4-(1-(1-(( 트리플루오로메틸 )술포닐)피페리딘-4-일)-1H- 피라졸 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-((trifluoromethyl)sulfonyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00713
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.50 (s, 1H), 8.41 (d, J = 34.0 Hz, 1H), 8.03 (d, J = 12.2 Hz, 2H), 7.36 (s, 1H), 6.75 (s, 1H), 3.94 (d, J = 13.2 Hz, 2H), 2.90 (d, J = 12.4 Hz, 1H), 2.26 - 1.99 (m, 6H), 0.86 - 0.76 (m, 4H).
MS(ESI+) m/z 483 (M+H)+
실시예 610: N-(4-(1-(1-(2- 시아노아세틸 ) 아제티딘 -3-일)-1H- 피라졸 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(2-cyanoacetyl)azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00714
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.52 (s, 1H), 8.56 (s, 1H), 8.12 (s, 1H), 8.07 (s, 1H), 7.38 (t, J = 3.0 Hz, 1H), 6.77 - 6.71 (m, 1H), 5.41 (t, J = 6.7 Hz, 1H), 4.64 (t, J = 8.6 Hz, 1H), 4.56 - 4.49 (m, 1H), 4.41 (t, J = 9.3 Hz, 1H), 4.28 (dd, J = 10.2, 5.4 Hz, 1H), 3.84 (d, J = 3.5 Hz, 2H), 2.04 - 1.96 (m, 1H), 0.84 - 0.77 (m, 4H).
MS(ESI+) m/z 390 (M+H)+
실시예 611: N-(4-(1-(1-( 시아노메틸 )피페리딘-4-일)-1H- 피라졸 -4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(cyanomethyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00715
1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 10.49 (s, 1H), 8.39 (s, 1H), 8.01 (d, J = 19.9 Hz, 3H), 7.39 - 7.30 (m, 1H), 6.73 (s, 1H), 4.44 - 4.18 (m, 2H), 2.93 (d, J = 11.1 Hz, 4H), 2.37 (s, 3H), 2.09 (d, J = 8.3 Hz, 7H), 0.80 (d, J = 18.3 Hz, 7H).
MS(ESI+) m/z 390 (M+H)+
실시예 612: N-(4-(1-(3-( 시아노메틸 ) 옥세탄 -3-일)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]사이클로프로판카복스아마이드 (N-(4-(1-(3-(cyanomethyl)oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00716
상기 합성된 N-(4-(1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로 프로판 카르복사미드 1.0 g (3.5 mmol)을 아세토니트릴에 용해시키고, 2-(옥세탄-3-일리덴)아세토니트릴 0.4 g (3.9 mmol), DBU 1.6 g (10.5 mmol)을 넣고, 30 - 40 oC 에서 16시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 물을 첨가한 후, 에틸아세테이트로 추출하였다. 추출한 용액을 무수 황산마그네슘으로 건조하고, 감압 농축하여 잔여물을 수득하였다. 잔여물은 실리카겔 컬럼크로마토그래피(DCM / MeOH = 30:1)에서 분리하여, N-(4-(1-(3-(시아노메틸)옥세탄-3-일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]사이클로프로판카복사미드를 수득하였다.
MS(ESI+) m/z 378 (M+H)+
실시예 613 내지 628
이하, 실시예 613 내지 실시예 628에서는, 실시예 612와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 613: N-(4-(1-(3-( 시아노메틸 ) 옥세탄 -3-일)-3- 메틸 -1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)oxetan-3-yl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00717
1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.54 (s, 1H), 7.81 (s, 1H), 7.35 - 7.26 (m, 1H), 6.46 (d, J = 3.8 Hz, 1H), 6.09 (s, 1H), 4.64 (d, J = 6.6 Hz, 1H), 4.53 (d, J = 6.6 Hz, 1H), 4.43 (t, J = 7.0 Hz, 2H), 3.27 (d, J = 18.0 Hz, 1H), 3.15 (d, J = 17.0 Hz, 1H), 3.08 (d, J = 3.8 Hz, 2H), 2.96 (s, 1H), 2.76 - 2.65 (m, 2H), 2.40 (dd, J = 4.6, 11.2 Hz, 1H), 2.02 (s, 1H), 0.91 (d, J = 6.9 Hz, 3H), 0.81 - 0.76 (m, 4H).
MS(ESI+) m/z 392 (M+H)+
실시예 614: tert-부틸3-(시아노메틸)-3-(4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-3,6-디히드로피리딘-1(2H)-일)아제티딘-1-카르복실레이트 ( tert - butyl 3-(cyanomethyl)-3-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)azetidine-1-carboxylate)의 합성
Figure pat00718
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.53 (s, 1H), 7.85 (s, 1H), 7.33 (t, J = 3.0 Hz, 1H), 6.53 (dd, J = 3.6, 1.8 Hz, 1H), 6.31 (d, J = 3.9 Hz, 1H), 3.83 (d, J = 35.4 Hz, 4H), 3.29 - 3.21 (m, 2H), 3.03 (s, 2H), 2.72 - 2.62 (m, 2H), 2.55 (s, 2H), 2.08 - 1.96 (m, 1H), 1.39 (s, 9H), 0.82-0.75 (m, 4H).
MS(ESI+) m/z 477 (M+H)+
실시예 615: N-(4-(1-(3-( 시아노메틸 ) 아제티딘 -3-일)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)사이클로프로판 카복사미드 (N-(4-(1-(3-(cyanomethyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00719
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.55 (s, 1H), 7.86 (s, 1H), 7.34 (t, J = 3.1 Hz, 1H), 6.53 (d, J = 2.6 Hz, 1H), 6.35 (s, 1H), 3.89 (d, J = 10.4 Hz, 2H), 3.76 (d, J = 10.4 Hz, 2H), 3.09 (s, 2H), 2.75 (t, J = 5.4 Hz, 2H), 2.58 (s, 2H), 2.02 (s, 1H), 0.87 - 0.73 (m, 4H).
MS(ESI+) m/z 377 (M+H)+
실시예 616: N-(4-(1-(3-(시아노메틸)-1-(에틸술포닐)아제티딘-3-일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00720
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.33 (t, J = 3.0 Hz, 1H), 6.54 (t, J = 2.7 Hz, 1H), 6.33 (d, J = 3.4 Hz, 1H), 4.00 (d, J = 8.2 Hz, 2H), 3.75 (d, J = 8.2 Hz, 2H), 3.28 (d, J = 3.3 Hz, 2H), 3.17 (q, J = 7.3 Hz, 2H), 3.11 (s, 2H), 2.70 (t, J = 5.4 Hz, 2H), 2.55 (s, 2H), 2.06 - 1.96 (m, 1H), 1.25 (t, J = 7.3 Hz, 3H), 0.82-0.75 (m, 4H).
MS(ESI+) m/z 469 (M+H)+
실시예 617: N-(4-(1-(3-(시아노메틸)-1-(이소프로필술포닐)아제티딘-3-일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-(isopropylsulfonyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00721
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.53 (s, 1H), 7.85 (s, 1H), 7.36 - 7.29 (m, 1H), 6.54 (dd, J = 3.5, 1.9 Hz, 1H), 6.32 (s, 1H), 4.01 (d, J = 7.9 Hz, 2H), 3.72 (d, J = 7.9 Hz, 2H), 3.24 (s, 2H), 3.10 (s, 2H), 2.67 (d, J = 6.0 Hz, 2H), 2.02 (s, 1H), 1.26 (d, J = 6.8 Hz, 6H), 1.17 (s, 1H), 0.80 (q, J = 3.4 Hz, 4H).
MS(ESI+) m/z 483 (M+H)+
실시예 618: N-(4-(1-(3-(시아노메틸)-1-((3-시아노프로필)술포닐)아제티딘-3-일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-((3-cyanopropyl)sulfonyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00722
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.53 (s, 1H), 7.86 (s, 1H), 7.34 (t, J = 2.9 Hz, 1H), 6.54 (dt, J = 5.0, 2.5 Hz, 1H), 6.32 (s, 1H), 4.00 (s, 1H), 3.78 (d, J = 8.2 Hz, 1H), 3.29 (d, J = 6.3 Hz, 2H), 3.14 (d, J = 12.4 Hz, 2H), 2.71 (d, J = 7.1 Hz, 2H), 2.66 (t, J = 7.3 Hz, 2H), 2.56 (s, 2H), 2.02 (d, J = 7.5 Hz, 2H), 0.82 - 0.74 (m, 4H).
MS(ESI+) m/z 508 (M+H)+
실시예 619: N-(4-(1-(3-( 시클로메틸 )술포닐) 아제티딘 -3-일)-1,2,3,6- 테트라히드로피리딘 -4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-((trifluoromethyl)sulfonyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00723
1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 10.54 (s, 1H), 7.86 (s, 1H), 7.34 (t, J = 3.0 Hz, 1H), 6.54 (dd, J = 3.6, 1.9 Hz, 1H), 6.32 (d, J = 3.8 Hz, 1H), 4.35 - 4.18 (m, 4H), 3.29 (d, J = 3.4 Hz, 2H), 3.15 (s, 2H), 2.71 (t, J = 5.5 Hz, 2H), 2.57 (s, 2H), 2.01 (d, J = 7.5 Hz, 1H), 0.83 - 0.77 (m, 4H).
MS(ESI+) m/z 509 (M+H)+
실시예 620: N-(4-(1-(3-(시아노메틸)-1-(피페리딘-4-일)아제티딘-3-일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-(piperidin-4-yl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00724
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 11.00 (s, 1H), 9.45 (s, 1H), 8.77 (s, 1H), 7.80 (s, 1H), 7.39 (s, 1H), 6.59 (s, 1H), 6.39 (s, 1H), 4.15 (d, J = 10.7 Hz, 2H), 3.70 - 3.58 (m, 2H), 3.56 (s, 1H), 3.54 - 3.46 (m, 2H), 3.46 - 3.33 (m, 2H), 2.97 (s, 2H), 2.84 (dd, J = 22.8, 10.4 Hz, 2H), 2.67 (s, 2H), 2.18 - 1.93 (m, 3H), 1.88 - 1.68 (m, 2H), 0.83 (m, 4H).
MS(ESI+) m/z 460 (M+H)+
실시예 621: N-(4-(1-(3-(시아노메틸)-1-(1-(4-(트리플루오로메틸)티아졸-2-카르보닐)피페리딘-4-일)아제티딘-3-일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-(1-(4-(trifluoromethyl)thiazole-2-carbonyl)piperidin-4-yl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00725
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.52 (s, 1H), 8.77 (s, 1H), 7.85 (s, 1H), 7.38 - 7.30 (m, 1H), 6.53 (s, 1H), 6.33 (s, 1H), 4.47-4.44 (m, 1H), 3.98-3.97 (m, 1H), 3.83-3.78 (m, 1H), 3.31-3.21 (m, 4H), 3.15-3.02 (m, 4H), 2.72 (m, 2H), 2.03 - 1.96 (m, 1H), 1.78-1.69 (m, 2H), 1.38-1.26 (m, 2H) 0.79 (dd, J = 9.4, 6.2 Hz, 4H).
MS(ESI+) m/z 639 (M+H)+
실시예 622: N-(4-(1-(1-(1-(2-( 시아노아세틸 )피페리딘-4-일)-3-( 시아노메틸 )아제티딘-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(1-(1-(2-cyanoacetyl)piperidin-4-yl)-3-(cyanomethyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00726
1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 10.53 (s, 1H), 7.84 (s, 1H), 7.33 (d, J = 3.3 Hz, 1H), 6.53 (s, 1H), 6.32 (s, 1H), 4.02 (s, 2H), 3.90-3.18 (m, 1H), 3.52 (m, 1H), 3.30 - 3.18 (m, 4H), 3.16-2.93 (m, 5H), 2.80 - 2.63 (m, 2H), 2.43-2.25 (m, 2H), 2.07-1.93 (m, 1H), 1.71-1.53 (m, 2H), 1.19-1.05 (m, 2H), 0.85-0.77 (m, 4H).
MS(ESI+) m/z 527 (M+H)+
실시예 623: N-(4-(1-(3-(시아노메틸)-1-((4-플루오로페닐)술포닐)아제티딘-3-일)-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-((4-fluorophenyl)sulfonyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00727
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.52 (s, 1H), 7.98 - 7.91 (m, 2H), 7.81 (s, 1H), 7.50 - 7.42 (m, 2H), 7.33 (dd, J = 3.5, 2.4 Hz, 1H), 6.48 (dd, J = 3.5, 1.9 Hz, 1H), 6.18 (d, J = 3.2 Hz, 1H), 3.76 (s, 4H), 3.07 (d, J = 3.5 Hz, 2H), 2.96 (s, 2H), 2.33 (s, 2H), 2.01 (d, J = 4.9 Hz, 1H), 0.79 (dt, J = 11.0, 3.5 Hz, 4H).
MS(ESI+) m/z 535 (M+H)+
실시예 624: 3-(시아노메틸)-3-(4-(6-(시클로프로판카르복사미도)-1H-피롤로[2,3-b]피리딘-4-일)-3,6-디히드로피리딘-1(2H)-일)-N-(2,2,2-트리플루오로에틸)아제티딘-1-카르복사미드 (3-(cyanomethyl)-3-(4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)-N-(2,2,2-trifluoroethyl)azetidine-1-carboxamide)의 합성
Figure pat00728
1H NMR (400 MHz, DMSO-d6) δ 11.42 (d, J = 2.6 Hz, 1H), 10.53 (s, 1H), 7.85 (s, 1H), 7.33 (dd, J = 3.5, 2.5 Hz, 1H), 6.53 (dd, J = 3.6, 1.9 Hz, 1H), 6.34 (d, J = 3.3 Hz, 1H), 4.25 (d, J = 9.2 Hz, 1H), 4.12 (d, J = 9.1 Hz, 1H), 3.93 (d, J = 10.3 Hz, 1H), 3.83 (d, J = 10.2 Hz, 1H), 3.41 (dd, J = 11.3, 3.4 Hz, 2H), 3.10 (s, 2H), 2.75 - 2.66 (m, 2H), 2.55 (d, J = 7.1 Hz, 2H), 2.01 (q, J = 8.5, 6.4 Hz, 1H), 0.79 (ddd, J = 11.3, 6.3, 2.6 Hz, 4H).
MS(ESI+) m/z 502 (M+H)+
실시예 625: N-(4-(1-(3-(시아노메틸)-1-(3,3,3-트리플루오로프로파노일)아제티딘-3-일)-1,2,3,6-테트라히드로피리딘-4-일)피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-(3,3,3-trifluoropropanoyl)azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00729
1H NMR (400 MHz, DMSO-d6) δ 11.44 - 11.35 (m, 1H), 10.53 (s, 1H), 7.85 (s, 1H), 7.36 - 7.27 (m, 1H), 7.17 (t, J = 6.3 Hz, 1H), 6.55 (dd, J = 3.9, 2.1 Hz, 1H), 6.33 (d, J = 3.6 Hz, 1H), 3.88 (d, J = 8.7 Hz, 2H), 3.83 - 3.72 (m, 4H), 3.08 (s, 2H), 2.69 (d, J = 5.7 Hz, 2H), 2.56 (s, 2H), 2.02 - 1.97 (m, 1H), 0.81 - 0.75 (m, 4H).
MS(ESI+) m/z 487 (M+H)+
실시예 626: N-(4-(1-(3-(시아노메틸)-1-(에틸술포닐)아제티딘-3-일)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(1-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00730
1H NMR (400 MHz, Chloroform-d) δ 11.40 (s, 1H), 10.54 (s, 1H), 7.80 (s, 1H), 7.36 - 7.25 (m, 1H), 6.45 (dd, J = 1.9, 3.5 Hz, 1H), 6.07 (s, 1H), 4.01 (dd, J = 8.3, 13.4 Hz, 1H), 3.90 (d, J = 8.3 Hz, 1H), 3.73 (dd, J = 8.1, 11.7 Hz, 2H), 3.23 - 3.07 (m, 4H), 2.95 (s, 1H), 2.77 - 2.65 (m, 1H), 2.07 (s, 3H), 1.99 (d, J = 6.5 Hz, 1H), 1.25 - 1.21 (m, 3H), 0.82 - 0.73 (m, 4H).
MS(ESI+) m/z 483 (M+H)+
실시예 627: (S)-N-(4-(1-(3-(시아노메틸)-1-(에틸술포닐)아제티딘-3-일)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00731
MS(ESI+) m/z 483 (M+H)+
실시예 628: (S)-N-(4-(1-(3-(시아노메틸)-1-((트리플루오로메틸)술포닐)아제티딘-3-일)-3-메틸-1,2,3,6-테트라히드로피리딘-4-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(1-(3-(cyanomethyl)-1-((trifluoromethyl)sulfonyl)azetidin-3-yl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00732
MS(ESI+) m/z 523 (M+H)+
실시예 629 내지 644
이하, 실시예 629 내지 실시예 644에서는, 실시예 1과 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 629: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐에탄술포네이트 (4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3- b]pyridin-4-yl)phenyl ethanesulfonate )의 합성
Figure pat00733
MS(ESI+) m/z 386 (M+H)+
실시예 630: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐4-플루오로벤젠술포네이트 (4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl 4- fluorobenzenesulfonate )의 합성
Figure pat00734
MS(ESI+) m/z 452 (M+H)+
실시예 631: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐 프로판-1- 술포네이트 (4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3- b]pyridin-4-yl)phenyl propane -1- sulfonate )의 합성
Figure pat00735
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.66 (s, 1H), 8.05 (s, 1H), 7.82 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.44 (s, 1H), 6.55 (s, 1H), 3.58 (t, J = 7.6 Hz, 2H), 2.05 (s, 1H), 1.89 (q, J = 8.0, 7.6 Hz, 2H), 1.06 (t, J = 7.5 Hz, 3H), 0.89 - 0.74 (m, 4H).
MS(ESI+) m/z 400 (M+H)+
실시예 632: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐 부탄-1- 술포네이트 (4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3- b]pyridin-4-yl)phenyl butane -1- sulfonate )의 합성
Figure pat00736
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.66 (s, 1H), 8.04 (s, 1H), 7.91 - 7.74 (m, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.44 (t, J = 3.2 Hz, 1H), 6.54 (s, 1H), 3.67 - 3.53 (m, 2H), 2.05 (s, 1H), 1.84 (s, 2H), 1.48 (q, J = 7.6 Hz, 2H), 0.93 (t, J = 7.3 Hz, 3H), 0.86 - 0.72 (m, 4H).
MS(ESI+) m/z 414 (M+H)+
실시예 633: 4 -(6-( 시클로프로판카르복사미도 ) 1H- 피롤로[2,3-b]피리딘 -4-일)페닐 프로판-2- 술포네이트 (4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3- b]pyridin-4-yl)phenyl propane -2- sulfonate )의 합성
Figure pat00737
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.66 (s, 1H), 8.04 (s, 1H), 7.82 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H), 7.44 (s, 1H), 6.60 - 6.50 (m, 1H), 3.87 - 3.73 (m, 1H), 2.05 (s, 1H), 1.47 (d, J = 6.5 Hz, 6H), 0.89 - 0.72 (m, 4H).
MS(ESI+) m/z 400 (M+H)+
실시예 634: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐 시클로헥산술포네이트 (4-(6-( cyclopropanecarboxamido )-1H- pyrrolo[2,3- b]pyridin-4-yl)phenyl cyclohexanesulfonate )의 합성
Figure pat00738
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.66 (s, 1H), 8.04 (s, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.44 (s, 1H), 6.54 (s, 1H), 3.61 (s, 1H), 2.24 (d, J = 12.1 Hz, 2H), 2.05 (s, 1H), 1.84 (d, J = 12.8 Hz, 2H), 1.70 - 1.53 (m, 3H), 1.40 (d, J = 13.4 Hz, 2H), 1.24 (t, J = 12.9 Hz, 1H), 0.87 - 0.74 (m, 4H).
MS(ESI+) m/z 440 (M+H)+
실시예 635: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐3-플루오로프로판-1-술포네이트 (4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl 3- fluoropropane -1- sulfonate )의 합성
Figure pat00739
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.66 (s, 1H), 8.05 (s, 1H), 7.86 - 7.76 (m, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 3.4 Hz, 1H), 6.54 (s, 1H), 4.61 (dt, J = 47.2, 6.0 Hz, 2H), 3.70 (t, J = 7.7 Hz, 2H), 2.27 (d, J = 25.7 Hz, 3H), 2.05 (s, 1H), 0.87 - 0.75 (m, 4H).
MS(ESI+) m/z 418 (M+H)+
실시예 636: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐 프로-2-엔-1- 술포네이트 (4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl prop -2- ene -1- sulfonate )의 합성
Figure pat00740
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.66 (s, 1H), 8.05 (s, 1H), 7.82 (d, J = 8.3 Hz, 2H), 7.57 - 7.47 (m, 2H), 7.45 - 7.38 (m, 1H), 6.60 - 6.45 (m, 1H), 5.95 (ddt, J = 17.2, 10.3, 6.9 Hz, 1H), 5.58 (dd, J = 31.7, 13.6 Hz, 2H), 4.44 (d, J = 7.2 Hz, 2H), 2.04 (d, J = 8.2 Hz, 1H), 0.82 (dt, J = 10.0, 5.6 Hz, 4H).
MS(ESI+) m/z 398 (M+H)+
실시예 637: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐 시클로헥실메탄술포네이트 (4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl cyclohexylmethanesulfonate )의 합성
Figure pat00741
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.66 (s, 1H), 8.04 (s, 1H), 7.82 (d, J = 8.2 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.44 (s, 1H), 6.54 (s, 1H), 3.51 (d, J = 6.5 Hz, 2H), 2.04 (s, 2H), 1.92 (d, J = 12.8 Hz, 2H), 1.69 (d, J = 11.0 Hz, 2H), 1.63 (s, 1H), 1.26 (t, J = 12.6 Hz, 2H), 1.20 - 1.07 (m, 3H), 0.80 (d, J = 11.1 Hz, 4H).
MS(ESI+) m/z 454 (M+H)+
실시예 638: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐 (테트라히드로푸란-3-일) 메탄술포네이트 (4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl (tetrahydrofuran-3-yl)methanesulfonate)의 합성
Figure pat00742
1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 10.66 (s, 1H), 8.04 (s, 1H), 7.82 (d, J = 7.9 Hz, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.44 (s, 1H), 6.54 (s, 1H), 3.92 (t, J = 7.8 Hz, 1H), 3.77 (d, J = 7.1 Hz, 3H), 3.68 (d, J = 8.0 Hz, 1H), 2.17 (s, 1H), 2.05 (s, 1H), 1.76 (d, J = 11.5 Hz, 1H), 1.15 - 1.03 (m, 1H), 0.82 (s, 4H).
MS(ESI+) m/z 442 (M+H)+
실시예 639: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐3-시아노프로판-1-술포네이트 (4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl 3- cyanopropane -1- sulfonate )의 합성
Figure pat00743
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.66 (s, 1H), 8.05 (s, 1H), 7.83 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 3.7 Hz, 1H), 6.54 (s, 1H), 3.69 (t, J = 7.5 Hz, 2H), 2.73 (t, J = 7.3 Hz, 2H), 2.21 (q, J = 7.7 Hz, 2H), 2.05 (s, 1H), 0.85 - 0.76 (m, 4H).
MS(ESI+) m/z 425 (M+H)+
실시예 640: 4 -(1-(3- 시아노프로필 )-6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)페닐3-시아노프로판-1-술포네이트 (4-(1-(3- cyanopropyl )-6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl 3-cyanopropane-1-sulfonate)의 합성
Figure pat00744
1H NMR (400 MHz, DMSO-d6) δ 10.94 (s, 1H), 8.28 (s, 1H), 7.82 (d, J = 8.3 Hz, 2H), 7.69 (d, J = 4.1 Hz, 1H), 7.57 (d, J = 8.2 Hz, 2H), 6.86 (s, 1H), 4.12 (d, J = 9.1 Hz, 2H), 3.71 (d, J = 8.0 Hz, 2H), 2.72 (d, J = 7.3 Hz, 2H), 2.63 (d, J = 5.1 Hz, 2H), 2.20 (s, 2H), 1.92 (s, 1H), 1.83 (t, J = 7.2 Hz, 2H), 0.85 (d, J = 6.5 Hz, 4H).
MS(ESI+) m/z 492 (M+H)+
실시예 641: N-(4-(4-((4- 플루오로벤질 ) 옥시 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((4- fluorobenzyl ) oxy ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00745
1H NMR (400 MHz, Methanol-d4) δ 11.49 (s, 1H), 10.58 (s, 1H), 7.99 (s, 1H), 7.75 - 7.63 (m, 2H), 7.55 (dd, J = 5.6, 8.4 Hz, 2H), 7.38 (t, J = 2.9 Hz, 1H), 7.29 - 7.13 (m, 5H), 6.52 (dd, J = 1.7, 3.5 Hz, 1H), 2.13 - 1.87 (m, 2H), 0.82 (td, J = 6.2, 12.0, 14.1 Hz, 5H).
MS(ESI+) m/z 402 (M+H)+
실시예 642: N-(4-(4-(2- 모르폴리노에톡시 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- morpholinoethoxy ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00746
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.58 (s, 1H), 7.99 (s, 1H), 7.69 - 7.61 (m, 2H), 7.38 (dd, J = 2.5, 3.5 Hz, 1H), 7.17 - 7.07 (m, 2H), 6.52 (dd, J = 1.9, 3.5 Hz, 1H), 4.17 (t, J = 5.7 Hz, 2H), 3.66 - 3.53 (m, 4H), 2.73 (t, J = 5.7 Hz, 2H), 2.09 - 1.99 (m, 1H), 1.24 (d, J = 3.6 Hz, 3H), 0.85 - 0.73 (m, 4H).
MS(ESI+) m/z 407 (M+H)+
실시예 643: N-(4-(4- 부톡시페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일) 시클로프로판카르복사미드 (N-(4-(4- butoxyphenyl )-1H- pyrrolo[2,3-b]pyridin -6-yl)cyclopropanecarboxamide)의 합성
Figure pat00747
1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.57 (s, 1H), 7.99 (s, 1H), 7.70 - 7.60 (m, 2H), 7.38 (d, J = 3.5 Hz, 1H), 7.13 - 7.05 (m, 2H), 6.53 (d, J = 3.5 Hz, 1H), 4.05 (t, J = 6.4 Hz, 2H), 2.04 (s, 1H), 1.78 - 1.67 (m, 2H), 1.47 (h, J = 7.3 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H), 0.87 - 0.75 (m, 4H).
MS(ESI+) m/z 350 (M+H)+
실시예 644: N-(6-(4-((6- 시아노피리딘 -3-일) 메톡시 )페닐)-9H- 푸린 -2-일) 시클로프로판카르복사미드 (N-(6-(4-((6- cyanopyridin -3- yl ) methoxy ) phenyl )-9H-purin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00748
1H NMR (400 MHz, DMSO-d6) δ 10.73 (s, 1H), 8.90 (d, J = 2.0 Hz, 1H), 8.84 (d, J = 8.8 Hz, 2H), 8.45 (s, 1H), 8.18 (dd, J = 8.1, 2.1 Hz, 1H), 8.10 (d, J = 7.9 Hz, 1H), 7.27 (d, J = 9.0 Hz, 2H), 5.38 (s, 2H), 2.20 - 2.13 (m, 1H), 0.84 (tt, J = 8.0, 3.1 Hz, 4H).
MS(ESI+) m/z 412 (M+H)+
실시예 645: N-(4-(4-( 에틸술폰아미도 ) 시클로헥실 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( ethylsulfonamido ) cyclohexyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00749
상기 합성된 N-(4-(4-아미노시클로헥스-1-엔-1-일)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 1 g을 MeOH 20 mL에 용해시키고, Pd/C 0.1 g을 넣고, 수소 기체 하에서, 실온으로 16시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 셀라이트 필터하고, MeOH로 세척하였다. 여액을 농축하여, 생성물 N-(4-(4-아미노시클로헥실)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
수득된 N-(4-(4-아미노시클로헥실)-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 출발물질로하여, 실시예 1과 동일한 방법으로 최종생성물 N-(4-(4-(에틸술폰아미도)시클로헥실)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
MS(ESI+) m/z 391 (M+H)+
실시예 646 내지 659
이하, 실시예 646 내지 실시예 659에서는, 실시예 645와 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 646: N-(4-(8-( 에틸술포닐 )-8- 아자비시클로[3.2.1]옥탄 -3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(8-(ethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00750
MS(ESI+) m/z 403 (M+H)+
실시예 647: N-(4-(8-( 시클로프로필술포닐 )-8- 아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(cyclopropylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00751
MS(ESI+) m/z 415 (M+H)+
실시예 648: N-(4-(8-((3- 플루오로프로필 )술포닐)-8- 아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-((3-fluoropropyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00752
MS(ESI+) m/z 435 (M+H)+
실시예 649: N-(4-(8-((3,4- 디플루오로페닐 )술포닐)-8- 아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-((3,4-difluorophenyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00753
MS(ESI+) m/z 487 (M+H)+
실시예 650: N-(4-(8-( 시클로프로판카르보닐 )-8- 아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(cyclopropanecarbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00754
MS(ESI+) m/z 379 (M+H)+
실시예 651: N-(4-(8- 펜타노일 -8- 아자비시클로[3.2.1]옥탄 -3-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(8-pentanoyl-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00755
MS(ESI+) m/z 395 (M+H)+
실시예 652: N-(4-(1-(2- 시아노아세틸 )피페리딘-4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-(2- cyanoacetyl ) piperidin -4- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00756
1H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 10.49 (s, 1H), 7.79 (s, 1H), 7.32 - 7.26 (m, 1H), 6.52 (dd, J = 3.5, 1.8 Hz, 1H), 4.54 - 4.46 (m, 1H), 4.10 (q, J = 18.8 Hz, 2H), 3.78 (d, J = 13.8 Hz, 1H), 3.28 - 3.14 (m, 3H), 2.78 (t, J = 12.6 Hz, 1H), 2.05 - 1.96 (m, 1H), 1.82 (dtt, J = 22.0, 13.6, 7.6 Hz, 3H), 1.60 - 1.47 (m, 1H), 0.78 (m, 4H).
MS(ESI+) m/z 352 (M+H)+
실시예 653: N-부틸-4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)피페리딘-1-카르복사미드 (N- butyl -4-(6-( cyclopropanecarboxamido )-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidine-1-carboxamide)의 합성
Figure pat00757
MS(ESI+) m/z 384 (M+H)+
실시예 654: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-N-(2,2,2-트리플루오로에틸)피페리딘-1-카르복사미드 (4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(2,2,2-trifluoroethyl)piperidine-1-carboxamide)의 합성
Figure pat00758
MS(ESI+) m/z 410 (M+H)+
실시예 655: tert -부틸 4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-히드록시피페리딘-1-카르복실레이트 ( tert - butyl 4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-hydroxypiperidine-1-carboxylate)의 합성
Figure pat00759
MS(ESI+) m/z 401 (M+H)+
실시예 656: tert -부틸 4-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3-플루오로피페리딘-1-카르복실레이트 ( tert - butyl 4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-fluoropiperidine-1-carboxylate)의 합성
Figure pat00760
MS(ESI+) m/z 403 (M+H)+
실시예 657: N-(4-(8-( 에틸카르바모티오일 )-8- 아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(ethylcarbamothioyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00761
MS(ESI+) m/z 398 (M+H)+
실시예 658: N-(4-(1-( 에틸카르바모티오일 )피페리딘-4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-( ethylcarbamothioyl ) piperidin -4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00762
MS(ESI+) m/z 372 (M+H)+
실시예 659: N-(4-(1-( 부틸카르바모티오일 )피페리딘-4-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(1-( butylcarbamothioyl ) piperidin -4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00763
1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 10.51 (s, 1H), 7.78 (s, 1H), 7.66 (t, J = 5.4 Hz, 1H), 7.29 (t, J = 2.7 Hz, 1H), 6.48 (dd, J = 1.8, 3.5 Hz, 1H), 4.89 - 4.75 (m, 2H), 3.51 (q, J = 6.6 Hz, 2H), 3.23 (t, J = 11.8 Hz, 1H), 3.09 (t, J = 12.9 Hz, 2H), 1.99 (d, J = 7.8 Hz, 1H), 1.83 (d, J = 12.9 Hz, 2H), 1.69 - 1.48 (m, 4H), 1.29 (h, J = 7.4 Hz, 2H), 0.90 (t, J = 7.3 Hz, 3H), 0.83 - 0.72 (m, 4H).
MS(ESI+) m/z 400 (M+H)+
실시예 660: N-(4-(4-( 메틸술포닐 )피페라진-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( methylsulfonyl ) piperazin -1- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00764
상기 합성된 N-(4-클로로-1-토실-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 1g (2.6 mmol)을 BuOH에 용해시키고, 1-(메틸술포닐)피페라진 0.6 g (3.9 mmol) 및 DIPEA 1 g (5.2 mmol)을 넣고, 120 ~ 130 oC에서 3시간동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온에서 냉각시키고, 물을 첨가한 후, 에틸아세테이트로 추출하였다. 추출한 용액은 무수 황산마그네슘으로 건조하고, 감압 농축하여 잔여물을 수득하였다. 잔여물은 실리카겔 컬럼크로마토그래피(DCM / MeOH = 30:1)에서 분리하여 농축하였다. 합성된 물질을 MeOH/THF (1:1) 용액에 용해시키고, 2N 수산화나트륨 수용액을 첨가하여, 30 ~ 40 oC에서 4 시간 동안 교반하였다. 반응이 완료되면, 상기 혼합물을 실온으로 냉각시키고, 교반하면서 포화된 염화암모늄 수용액을 첨가하였다. 생성된 고체를 여과하여 생성물인 N-(4-(4-(메틸술포닐)피페라진-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드를 수득하였다.
MS(ESI+) m/z 364 (M+H)+
실시예 661 내지 704
이하, 실시예 661 내지 실시예 704에서는, 실시예 661과 동일한 방법으로 합성하거나, 반응식 1 및 제조하고자 하는 화합물의 구조를 고려하여 적절한 반응물을 사용하여 합성하였다.
실시예 661: N-(4-(8-( 메틸술포닐 )-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(methylsulfonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00765
1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 10.32 (s, 1H), 7.35 (s, 1H), 7.11 (t, J = 3.0 Hz, 1H), 6.46 (dd, J = 3.7, 2.0 Hz, 1H), 4.30 (d, J = 4.0 Hz, 2H), 3.80 (d, J = 10.3 Hz, 2H), 3.08 (d, J = 11.9 Hz, 2H), 3.04 (s, 3H), 1.99 (s, 3H), 1.86 (d, J = 7.4 Hz, 2H), 0.82 - 0.71 (m, 4H).
MS(ESI+) m/z 390 (M+H)+
실시예 662: N-(4-(4-(((1- 시아노시클로프로필 ) 메틸 )술포닐)피페라진-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(((1-cyanocyclopropyl)methyl)sulfonyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00766
MS(ESI+) m/z 429 (M+H)+
실시예 663: N-(4-(4-((3- 플루오로프로필 )술포닐)피페라진-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-((3-fluoropropyl)sulfonyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00767
1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 10.39 (s, 1H), 7.43 (s, 1H), 7.16 (s, 1H), 6.43 (s, 1H), 4.61 (t, J = 6.0 Hz, 1H), 4.49 (t, J = 6.0 Hz, 1H), 3.60 (s, 1H), 3.40 (d, J = 6.3 Hz, 5H), 3.24 - 3.17 (m, 2H), 2.15 - 1.98 (m, 3H), 1.76 (s, 1H), 0.78 (dd, J = 6.1, 11.2 Hz, 4H).
MS(ESI+) m/z 410 (M+H)+
실시예 664: N-(4-(8-((3- 시아노프로필 )술포닐)-3,8- 디아자비시클로[3.2.1] 옥탄-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-((3-cyanopropyl)sulfonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00768
1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 10.31 (s, 1H), 7.36 (s, 1H), 7.17 - 7.05 (m, 1H), 6.46 (dd, J = 1.9, 3.6 Hz, 1H), 4.31 (s, 2H), 3.80 (d, J = 11.6 Hz, 2H), 3.27 (d, J = 7.7 Hz, 2H), 3.11 (d, J = 11.5 Hz, 2H), 2.72 - 2.64 (m, 2H), 2.04 (q, J = 7.4 Hz, 3H), 1.89 (s, 2H), 0.84 - 0.72 (m, 4H).
MS(ESI+) m/z 443 (M+H)+
실시예 665: N-(4-(8-(((1-(시아노메틸)시클로프로필)메틸)술포닐)-3,8-디아자비시클로[3.2.1]옥탄-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-((1-(cyanomethyl)cyclopropyl)methyl)sulfonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00769
1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 10.31 (s, 1H), 7.35 (s, 1H), 7.11 (dd, J = 2.5, 3.6 Hz, 1H), 6.46 (dd, J = 2.0, 3.6 Hz, 1H), 4.33 (s, 2H), 3.84 - 3.69 (m, 2H), 3.12 (d, J = 11.8 Hz, 2H), 2.83 (s, 2H), 2.00 (s, 1H), 1.89 (d, J = 3.7 Hz, 2H), 0.88 - 0.81 (m, 2H), 0.76 (ddt, J = 3.0, 5.1, 12.9 Hz, 4H), 0.71 - 0.65 (m, 2H).
MS(ESI+) m/z 469 (M+H)+
실시예 666: N-(4-(8-((4,4,4- 트리플루오로부틸 )술포닐)-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-((4,4,4-trifluorobutyl)sulfonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00770
1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 10.31 (s, 1H), 7.35 (s, 1H), 7.11 (dd, J = 2.5, 3.6 Hz, 1H), 6.46 (dd, J = 2.0, 3.6 Hz, 1H), 4.33 (s, 2H), 3.84 - 3.69 (m, 2H), 3.12 (d, J = 11.8 Hz, 2H), 2.83 (s, 2H), 2.00 (s, 1H), 1.89 (d, J = 3.7 Hz, 2H), 0.88 - 0.81 (m, 2H), 0.76 (ddt, J = 3.0, 5.1, 12.9 Hz, 4H), 0.71 - 0.65 (m, 2H).
MS(ESI+) m/z 486 (M+H)+
실시예 667: N-(4-(8-(((1- 시아노시클로프로필 ) 메틸 )술포닐)-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(((1-cyanocyclopropyl)methyl)sulfonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00771
1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 10.30 (s, 1H), 7.35 (s, 1H), 7.11 (dd, J = 2.4, 3.6 Hz, 1H), 6.45 (dd, J = 1.9, 3.6 Hz, 1H), 4.68 (s, 1H), 4.40 - 4.28 (m, 1H), 3.85 - 3.75 (m, 1H), 3.65 (d, J = 11.2 Hz, 1H), 3.04 (dd, J = 11.3, 42.2 Hz, 2H), 2.83 - 2.57 (m, 2H), 1.98 (d, J = 7.0 Hz, 1H), 1.97 - 1.81 (m, 4H), 1.24 - 1.17 (m, 2H), 1.02 - 0.90 (m, 2H), 0.82 - 0.70 (m, 4H).
MS(ESI+) m/z 455 (M+H)+
실시예 668: N-(4-(4-( 프로필술포닐 )피페라진-1-일)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-( propylsulfonyl ) piperazin -1- yl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00772
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 10.05 (s, 1H), 7.09 (d, J = 3.6 Hz, 1H), 6.57 (d, J = 3.6 Hz, 1H), 4.02 - 3.90 (m, 4H), 3.28 (s, 4H), 3.08 - 3.01 (m, 2H), 2.18 (s, 1H), 1.70 (q, J = 7.5 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.81 - 0.72 (m, 4H).
MS(ESI+) m/z 393 (M+H)+
실시예 669: N-(4-(8-( 에틸술포닐 )-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(8-(ethylsulfonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00773
MS(ESI+) m/z 405 (M+H)+
실시예 670: (R)-N-(4-(3-( 프로필술폰아미도 ) 피롤리딘 -1-일)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 ((R)-N-(4-(3-(propylsulfonamido)pyrrolidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00774
1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 9.87 (s, 1H), 7.49 (d, J = 6.4 Hz, 1H), 7.06 - 6.95 (m, 1H), 6.48 (s, 1H), 4.07 - 3.57 (m, 7H), 3.06 (dd, J = 6.4, 9.1 Hz, 2H), 2.23 (s, 1H), 1.97 (s, 1H), 1.68 (q, J = 7.6 Hz, 2H), 1.17 (s, 2H), 0.98 (t, J = 7.4 Hz, 3H).
MS(ESI+) m/z 393 (M+H)+
실시예 671: (R)-N-(4-(3-( 알릴술폰아미도 ) 피롤리딘 -1-일)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 ((R)-N-(4-(3-(allylsulfonamido)pyrrolidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00775
1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.89 (s, 1H), 7.62 (s, 1H), 7.05 - 6.97 (m, 1H), 6.53 - 6.42 (m, 1H), 5.89 - 5.74 (m, 4H), 5.40 (t, J = 13.6 Hz, 3H), 3.94 - 3.85 (m, 7H), 2.23 (s, 1H), 1.94 (d, J = 28.2 Hz, 1H), 0.80 - 0.73 (m, 4H).
MS(ESI+) m/z 391 (M+H)+
실시예 672: (R)-N-(4-(3-(N- 메틸에틸술폰아미도 ) 피롤리딘 -1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 ((R)-N-(4-(3-(N-methylethylsulfonamido)pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00776
1H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 10.17 (s, 1H), 7.09 - 6.94 (m, 2H), 6.54 (dd, J = 3.6, 1.9 Hz, 1H), 4.52 (p, J = 8.0 Hz, 1H), 3.73 (t, J = 8.9 Hz, 2H), 3.56 (q, J = 8.2 Hz, 2H), 3.22 - 3.09 (m, 2H), 2.82 (s, 3H), 2.18 (q, J = 8.2, 7.7 Hz, 2H), 1.99 (s, 1H), 1.22 (t, J = 7.3 Hz, 3H), 0.84 - 0.63 (m, 4H).
MS(ESI+) m/z 392 (M+H)+
실시예 673: N-(4-(4-( 모르폴리노술포닐 )피페라진-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-( morpholinosulfonyl ) piperazin -1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00777
1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 10.39 (s, 1H), 7.43 (s, 1H), 7.20 - 7.06 (m, 1H), 6.43 (dd, J = 1.9, 3.6 Hz, 1H), 3.63 (t, J = 4.6 Hz, 4H), 3.16 (d, J = 5.1 Hz, 8H), 2.00 (s, 1H), 0.83-075 (m, 4H).
MS(ESI+) m/z 435 (M+H)+
실시예 674: N-(4-(4-( N,N - 디메틸술파모일 )피페라진-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(N,N-dimethylsulfamoyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00778
1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 10.39 (s, 1H), 7.43 (s, 1H), 7.15 (t, J = 3.0 Hz, 1H), 6.43 (dd, J = 1.9, 3.6 Hz, 1H), 3.17 (d, J = 5.2 Hz, 8H), 2.81 (s, 6H), 2.00 (s, 1H), 0.85 - 0.70 (m, 4H).
MS(ESI+) m/z 393 (M+H)+
실시예 675: N-(4-(4-(2- 시아노아세트아미노 )피페리딘-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- cyanoacetamido ) piperidin -1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00779
MS(ESI+) m/z 367 (M+H)+
실시예 676: N-(4-(4-(2- 시아노아세틸 )피페라진-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(2- cyanoacetyl ) piperazin -1- yl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00780
1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 10.35 (s, 1H), 7.40 (s, 1H), 7.14 (t, J = 3.0 Hz, 1H), 6.44 (dd, J = 1.9, 3.6 Hz, 1H), 4.10 (s, 2H), 3.66 (s, 2H), 3.56 (s, 2H), 3.38 (s, 4H), 2.08 (s, 3H), 2.00 (s, 1H), 0.82 - 0.73 (m, 4H).
MS(ESI+) m/z 353 (M+H)+
실시예 677: N-(4-(8-(2- 시아노아세틸 )-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]-시클로프로판카르복사미드 (N-(4-(8-(2-cyanoacetyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00781
1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 10.33 (s, 1H), 7.36 (s, 1H), 7.15 - 7.09 (m, 1H), 6.45 (dd, J = 3.8, 2.0 Hz, 1H), 4.64 (s, 1H), 4.33 (d, J = 6.5 Hz, 1H), 4.09 (d, J = 4.5 Hz, 2H), 3.81 (d, J = 11.4 Hz, 1H), 3.65 (d, J = 11.6 Hz, 1H), 3.16 (d, J = 11.8 Hz, 1H), 2.98 (d, J = 11.4 Hz, 1H), 2.00 (q, J = 7.2 Hz, 2H), 1.90 (d, J = 5.5 Hz, 1H), 1.87 (s, 2H), 0.82 - 0.72 (m, 4H).
MS(ESI+) m/z 379 (M+H)+
실시예 678: N-(4-(3-(2- 시아노아세틸 )-3,8- 디아자비시클로[3.2.1]옥탄 -8-일)-1H-피롤로[2,3-b]피리딘-6-일)-시클로프로판카르복사미드 (N-(4-(3-(2-cyanoacetyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00782
1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 10.33 (s, 1H), 7.39 (s, 1H), 7.17 - 7.09 (m, 1H), 6.50 (dd, J = 1.9, 3.6 Hz, 1H), 4.61 - 4.46 (m, 2H), 4.18 (d, J = 18.9 Hz, 1H), 4.10 - 3.98 (m, 2H), 3.87 (d, J = 18.9 Hz, 1H), 1.97 - 1.84 (m, 3H), 1.27 - 1.14 (m, 4H), 0.77 (ddt, J = 3.1, 5.2, 10.9 Hz, 4H).
MS(ESI+) m/z 379 (M+H)+
실시예 679: N-(4-(( 1S,4S )-5-(2- 시아노아세틸 )-2,5- 디아자비시클로[2.2.1]헵탄 -2-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-((1S,4S)-5-(2-cyanoacetyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00783
1H NMR (400 MHz, DMSO-d6) δ 11.01 (d, J = 8.5 Hz, 1H), 10.19 (s, 1H), 7.09 (s, 1H), 7.02 (ddd, J = 6.6, 3.6, 2.4 Hz, 1H), 6.43 (ddd, J = 13.9, 3.5, 1.9 Hz, 1H), 4.84 - 4.61 (m, 2H), 4.09 - 4.05 (m, 1H), 4.04 - 3.97 (m, 1H), 3.90 - 3.72 (m, 3H), 3.56 (d, J = 28.4 Hz, 1H), 3.43 (d, J = 6.6 Hz, 1H), 3.17 (d, J = 5.1 Hz, 1H), 2.12 - 2.07 (m, 1H), 1.24 (s, 1H), 0.80 - 0.77 (m, 2H), 0.74 (dd, J = 7.6, 3.5 Hz, 2H).
MS(ESI+) m/z 365 (M+H)+
실시예 680: N-(4-(( 1S,4S )-5-(3- 시아노프로파노일 )-2,5- 디아자비시클로[2.2.1]헵탄 -2-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-((1S,4S)-5-(3-cyanopropanoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00784
1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 10.19 (s, 1H), 7.09 (s, 1H), 7.02 (td, J = 3.9, 2.4 Hz, 1H), 6.44 (ddd, J = 6.3, 3.7, 2.0 Hz, 1H), 4.86 - 4.65 (m, 2H), 3.87 (d, J = 9.2 Hz, 1H), 3.68 - 3.48 (m, 2H), 3.43 (s, 1H), 2.89 - 2.65 (m, 2H), 2.57 (dd, J = 16.5, 9.4 Hz, 2H), 2.07 (s, 1H), 0.79 - 0.71 (m, 4H).
MS(ESI+) m/z 379 (M+H)+
실시예 681: N-(4-(( 1R,4R )-5-(2- 시아노아세틸 )-2,5- 디아자비시클로[2.2.1]헵탄 -2-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-((1R,4R)-5-(2-cyanoacetyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00785
1H NMR (400 MHz, DMSO-d6) δ 11.03 (d, J = 8.7 Hz, 1H), 10.22 (s, 1H), 7.09 (s, 1H), 7.03 (dt, J = 6.7, 3.1 Hz, 1H), 6.43 (d, J = 14.4 Hz, 1H), 4.83 - 4.60 (m, 2H), 4.08 (q, J = 18.8 Hz, 2H), 3.90 - 3.72 (m, 2H), 3.61 - 3.49 (m, 1H), 3.43 (d, J = 6.4 Hz, 1H), 2.04 (dt, J = 45.1, 6.5 Hz, 2H), 1.89 (d, J = 9.3 Hz, 1H), 0.81 - 0.69 (m, 4H).
MS(ESI+) m/z 365 (M+H)+
실시예 682: N-(4-(( 1R,4R )-5-(3- 시아노프로파노일 )-2,5- 디아자비시클로[2.2.1]헵탄 -2-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-((1R,4R)-5-(3-cyanopropanoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00786
1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 10.22 (s, 1H), 7.09 (s, 1H), 7.02 (q, J = 3.7 Hz, 1H), 6.43 (s, 1H), 4.84 - 4.66 (m, 2H), 3.87 (d, J = 9.0 Hz, 1H), 3.66 - 3.47 (m, 2H), 3.16 (d, J = 5.2 Hz, 2H), 2.11 - 1.93 (m, 4H), 1.89 (d, J = 10.0 Hz, 1H), 0.75 (ddd, J = 13.6, 6.3, 3.9 Hz, 4H).
MS(ESI+) m/z 379 (M+H)+
실시예 683: N-(4-(4-(2-(1- 시아노시클로프로필 )아세틸)피페라진-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1-cyanocyclopropyl)acetyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00787
1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 10.37 (s, 1H), 7.40 (s, 1H), 7.22 - 7.10 (m, 1H), 6.50 - 6.40 (m, 1H), 3.68 (s, 2H), 3.56 (s, 2H), 2.73 (d, J = 6.0 Hz, 4H), 2.00 (s, 1H), 0.95 - 0.90 (m, 2H), 0.82 - 0.73 (m, 4H).
MS(ESI+) m/z 393 (M+H)+
실시예 684: N-(4-(4-(3- 시아노프로파노일 )피페라진-1-일)-1H- 피롤로[2,3-b] 피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(3- cyanopropanoyl ) piperazin -1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00788
1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 10.37 (s, 1H), 7.40 (s, 1H), 7.20 - 7.06 (m, 1H), 6.56 - 6.38 (m, 1H), 3.65 (d, J = 17.9 Hz, 4H), 2.92 - 2.66 (m, 4H), 2.66 - 2.53 (m, 4H), 2.00 (s, 1H), 0.81-0.71 (m, 4H).
MS(ESI+) m/z 367 (M+H)+
실시예 685: N-(4-(6-(2- 시아노아세틸 )-3,6- 디아자비시클로[3.1.1]헵탄 -3-일)-1H-피롤로[2,3-b]-피리딘-6-일)시클로프로판카르복사미드 (N-(4-(6-(2-cyanoacetyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00789
MS(ESI+) m/z 365 (M+H)+
실시예 686: N-(4-(8-(3- 시아노벤조일 )-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-1H-피롤로[2,3-b]-피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(3-cyanobenzoyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00790
MS(ESI+) m/z 441 (M+H)+
실시예 687: N-(4-(4-(2- 시아노아세틸 )피페라진-1-일)-7H- 피롤로[2,3-d]피리미딘 -2-일)시클로프로판카르복사미드 (N-(4-(4-(2- cyanoacetyl ) piperazin -1- yl )-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00791
1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 10.03 (s, 1H), 7.07 (t, J = 2.9 Hz, 1H), 6.56 (d, J = 2.8 Hz, 1H), 4.10 (s, 2H), 3.91 (dt, J = 5.1, 19.7 Hz, 3H), 3.57 (dt, J = 5.5, 41.4 Hz, 4H), 2.20 (d, J = 10.8 Hz, 1H), 0.76 (dt, J = 3.8, 11.0 Hz, 4H).
MS(ESI+) m/z 354 (M+H)+
실시예 688: N-(4-(8-(2- 시아노아세틸 )-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-7H-피롤로[2,3-d]피리미딘-2-시클로프로판카르복사미드 (N-(4-((8-(2-cyanoacetyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00792
MS(ESI+) m/z 380 (M+H)+
실시예 689: N-(4-(8-(2-(1- 시아노시클로프로필 )아세틸)-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(8-(2-(1-cyanocyclopropyl)acetyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00793
MS(ESI+) m/z 420 (M+H)+
실시예 690: 4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-N-(2,2,2-트리플루오로에틸)피페라진-1-카르복사미드 (4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(2,2,2-trifluoroethyl)piperazine-1-carboxamide)의 합성
Figure pat00794
1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 10.36 (s, 1H), 7.40 (s, 1H), 7.25 (t, J = 6.1 Hz, 1H), 7.14 (d, J = 3.5 Hz, 1H), 6.88 (s, 1H), 6.44 (s, 1H), 3.85 (dt, J = 5.9, 10.8 Hz, 4H), 3.59 (d, J = 6.6 Hz, 2H), 3.54 (s, 4H), 2.00 (s, 1H), 0.81-0.74 (m, 4H).
MS(ESI+) m/z 411 (M+H)+
실시예 691: 3 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-N-(2,2,2-트리플루오로에틸)-3,8-디아자바이시클로[3.2.1]옥탄-8-카르복사미드 (3-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(2,2,2-trifluoroethyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide)의 합성
Figure pat00795
1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 10.30 (s, 1H), 7.33 (d, J = 6.9 Hz, 2H), 7.10 (dd, J = 2.5, 3.6 Hz, 1H), 6.45 (dd, J = 1.9, 3.6 Hz, 1H), 4.42 (s, 2H), 3.93 - 3.78 (m, 2H), 3.70 - 3.61 (m, 2H), 3.03 (d, J = 11.3 Hz, 2H), 1.99 (s, 1H), 1.86 (s, 4H), 0.83 - 0.71 (m, 4H).
MS(ESI+) m/z 437 (M+H)+
실시예 692: tert - 부틸4 -(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)피페라진-1-카르복실레이트 ( tert - butyl 4-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridine-4-yl)piperazin-1-carboxylate)의 합성
Figure pat00796
MS(ESI+) m/z 386 (M+H)+
실시예 693: tert -부틸 3-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,8-디아자비시클로[3.2.1]옥탄-8-카르복실레이트 ( tert - butyl 3-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate)의 합성
Figure pat00797
1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 10.31 (s, 1H), 7.34 (s, 1H), 7.11 (d, J = 3.0 Hz, 1H), 6.46 (d, J = 3.1 Hz, 1H), 4.26 (d, J = 5.3 Hz, 2H), 3.71 (d, J = 11.5 Hz, 2H), 3.00 (d, J = 12.0 Hz, 2H), 1.99 (s, 1H), 1.85 (s, 4H), 1.42 (s, 9H), 0.89 - 0.67 (m, 4H).
MS(ESI+) m/z 412 (M+H)+
실시예 694: tert -부틸 8-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)-3,8-디아자비시클로[3.2.1]옥탄-3-카르복실레이트 ( tert - butyl 8-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate)의 합성
Figure pat00798
1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 10.30 (s, 1H), 7.36 (s, 1H), 7.09 (dd, J = 2.5, 3.6 Hz, 1H), 6.49 (dd, J = 2.0, 3.7 Hz, 1H), 4.49 (s, 2H), 3.68 (t, J = 16.9 Hz, 3H), 3.42 (d, J = 10.5 Hz, 1H), 3.20 - 3.12 (m, 1H), 3.02 (d, J = 12.4 Hz, 1H), 2.03 - 1.92 (m, 3H), 1.39 (s, 9H), 0.80 - 0.72 (m, 4H).
MS(ESI+) m/z 412 (M+H)+
실시예 695: tert -부틸 3-(2-( 시클로프로판카르복사미도 )-7H- 피롤로[2,3-d]피리미딘 -4-일)-3,8-디아자비시클로[3.2.1]옥탄-8-카르복실레이트 ( tert - butyl 3-(2-(cyclopropanecarboxamido)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate)의 합성
Figure pat00799
MS(ESI+) m/z 413 (M+H)+
실시예 696: tert -부틸 (R)-(1-(2-( 시클로프로판카르복사미도 )-7H- 피롤로[2,3-d]피리미딘 -4-일)피롤리딘-3-일)카르바메이트 ( tert - butyl (R)-(1-(2-(cyclopropanecarboxamido)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl)carbamate)의 합성
Figure pat00800
MS(ESI+) m/z 387 (M+H)+
실시예 697: tert -부틸 (R)-(1-(6-( 시클로프로판카르복사미도 )-1H- 피롤로[2,3-b]피리딘 -4-일)피롤리딘-3-일)카르바메이트 ( tert - butyl (R)-(1-(6-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-yl)carbamate)의 합성
Figure pat00801
MS(ESI+) m/z 386 (M+H)+
실시예 698: N-(4-(4-( 이소티아졸 -5- 일메틸 )피페라진-1-일)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판카르복사미드 (N-(4-(4-(isothiazol-5-ylmethyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00802
1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 10.34 (s, 1H), 8.49 (d, J = 1.7 Hz, 1H), 7.39 (s, 1H), 7.31 (d, J = 1.6 Hz, 1H), 7.11 (t, J = 3.0 Hz, 1H), 6.39 (dd, J = 1.9, 3.6 Hz, 1H), 4.11 (t, J = 5.2 Hz, 1H), 3.96 (s, 2H), 3.17 (d, J = 5.2 Hz, 3H), 2.66 (t, J = 4.7 Hz, 4H), 2.00 (s, 1H), 0.82-0.74 (m, 4H).
MS(ESI+) m/z 383 (M+H)+
실시예 699: (S)-N-(4-(4-((2,2- 디플루오로시클로프로필 ) 메틸 )피페라진-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 ((S)-N-(4-(4-((2,2-difluorocyclopropyl)methyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00803
1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.57 (s, 1H), 7.67 (s, 1H), 7.31 (t, J = 3.0 Hz, 1H), 6.24 (tt, J = 1.5, 3.3 Hz, 1H), 4.14 (dd, J = 1.2, 3.5 Hz, 2H), 4.07 - 3.94 (m, 2H), 3.70 (t, J = 5.7 Hz, 1H), 3.57 (t, J = 5.7 Hz, 1H), 2.34 (s, 1H), 2.05 - 1.95 (m, 1H), 1.52 (s, 3H), 1.24 (d, J = 8.3 Hz, 1H), 0.83 - 0.75 (m, 4H).
MS(ESI+) m/z 376 (M+H)+
실시예 700: N-(4-(4-(3-( 시아노메틸 )-1-( 에틸술포닐 ) 아제티딘 -3-일)피페라진-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00804
MS(ESI+) m/z 472 (M+H)+
실시예 701: N-(4-(8-(3-( 시아노메틸 )-1-( 에틸술포닐 ) 아제티딘 -3-일)-3,8- 디아자비시클로[3.2.1]옥탄 -3-일)-2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00805
1H NMR (400 MHz, DMSO-d6) δ 10.29 (s, 1H), 9.46 (s, 1H), 7.49 - 7.37 (m, 2H), 6.71 - 6.60 (m, 1H), 4.54 (d, J = 9.2 Hz, 2H), 4.24 (d, J = 9.1 Hz, 2H), 4.14 (s, 2H), 3.87 - 3.74 (m, 2H), 3.19 (q, J = 7.3 Hz, 2H), 2.37 (q, J = 7.4 Hz, 2H), 1.99 (s, 5H), 1.25 - 1.21 (m, 3H), 1.05 (t, J = 7.4 Hz, 3H), 0.82-0.74 (m, 4H).
MS(ESI+) m/z 498 (M+H)+
실시예 702: N-(4-(4-(2-(1,1- 디옥시티오모르폴리노 )-2- 옥소에틸 )피페라진-1-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(4-(2-(1,1-dioxidothiomorpholino)-2-oxoethyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00806
MS(ESI+) m/z 461 (M+H)+
실시예 703: N-(4-(8-(2-((R)-2-시아노피롤리딘-1-일)-2-옥소에틸)-3,8-디아자바이시클로[3.2.1]옥탄-3-일)-1H-피롤로[2,3-b]피리딘-6-일)시클로프로판카르복사미드 (N-(4-(8-(2-((R)-2-cyanopyrrolidin-1-yl)-2-oxoethyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide)의 합성
Figure pat00807
1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 9.96 (s, 1H), 7.01 (t, J = 2.9 Hz, 1H), 6.53 (d, J = 3.3 Hz, 1H), 4.31 (dt, J = 8.5, 4.3 Hz, 2H), 3.74 (dt, J = 9.8, 6.3 Hz, 1H), 3.63 (s, 2H), 3.56 (s, 1H), 3.28 - 3.14 (m, 4H), 2.24 - 2.11 (m, 2H), 1.94 - 1.83 (m, 4H), 1.54 (d, J = 8.7 Hz, 2H), 0.75 (qd, J = 8.5, 4.8 Hz, 4H).
MS(ESI+) m/z 448 (M+H)+
실시예 704: N-(4-(8-(2-(1,1-디옥시티오모르폴리노)-2-옥소에틸)-3,8-디아자비시클로[3.2.1]옥탄-3-일)-7H-피롤로[2,3-d]피리미딘-2-일)시클로프로판카르복사미드 (N-(4-(8-(2-(1,1-dioxidothiomorpholino)-2-oxoethyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)cyclopropanecarboxamide)의 합성
Figure pat00808
MS(ESI+) m/z 488 (M+H)+
실시예 705: (S)-3-(4-(6-아미노-1H- 피롤로[2,3-b]피리딘 -4-일)-3- 메틸 -3,6-디히드로피리딘-1(2H)-일)-3-옥소프로판니트릴 ((S)-3-(4-(6-amino-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methyl-3,6-dihydropyridin-1(2H)-yl)-3-oxopropanenitrile)의 합성
Figure pat00809
MS(ESI+) m/z 296 (M+H)+
실시예 706: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로펜탄 카르복사미드 (N-(4-(4-( ethylsulfonamido )-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopentanecarboxamide)의 합성
Figure pat00810
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 10.29 (s, 1H), 9.83 (s, 1H), 8.04 (s, 1H), 7.58 (d, J = 9.0 Hz, 3H), 7.43 (s, 1H), 6.56 (s, 1H), 3.18 (q, J = 7.5 Hz, 2H), 2.97 (s, 1H), 1.85 (s, 2H), 1.69 (s, 4H), 1.55 (s, 2H), 1.29 (t, J = 7.7 Hz, 4H).
MS(ESI+) m/z 417 (M+H)+
실시예 707: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로헥산 카르복사미드 (N-(4-(4-( ethylsulfonamido )-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclohexanecarboxamide)의 합성
Figure pat00811
1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 10.21 (s, 1H), 8.22 (s, 1H), 8.03 (s, 1H), 7.56 (s, 3H), 7.42 (s, 2H), 6.55 (s, 1H), 3.17 (q, 2H), 2.36 (s, 1H), 1.76 (d, J = 23.4 Hz, 4H), 1.68 - 1.56 (m, 2H), 1.41 (d, J = 11.7 Hz, 4H), 1.29 (t, J = 7.1 Hz, 4H).
MS(ESI+) m/z 421 (M+H)+
실시예 708: N-(4-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)프로피온아미드 (N-(4-(4-( ethylsulfonamido )-3- fluorophenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)propionamide)의 합성
Figure pat00812
1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.14 (s, 1H), 7.94 (s, 1H), 7.47 - 7.36 (m, 1H), 7.33 (s, 1H), 7.26 (t, J = 9.0 Hz, 2H), 6.56 (s, 1H), 2.79 (q, J = 8.0 Hz, 2H), 2.41 (q, J = 7.7 Hz, 2H), 1.17 (t, 3H), 1.09 (t, J = 7.2 Hz, 3H).
MS(ESI+) m/z 433 (M+H)+
실시예 709: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)-2-페닐아세트아미드 (N-(4-(4-( ethylsulfonamido )-3- fluorophenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-phenylacetamide)의 합성
Figure pat00813
1H NMR (400 MHz, DMSO-d6) δ 11.71 - 11.50 (s, 1H), 10.58 (s, 1H), 9.81 (s, 1H), 8.00 (s, 1H), 7.56 (d, J = 10.0 Hz, 3H), 7.45 (s, 1H), 7.41 - 7.27 (m, 5H), 7.25 (d, J = 7.4 Hz, 1H), 6.56 (s, 1H), 3.74 (s, 2H), 3.23 - 3.04 (q, 2H), 1.35 - 1.25 (t, 3H).
MS(ESI+) m/z 494 (M+H)+
실시예 710: N-(4-(4-( 에틸설폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)아세트아미드 (N-(4-(4-( ethylsulfonamido )-3- fluorophenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)acetamide)의 합성
Figure pat00814
1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 10.34 (s, 1H), 9.79 (s, 1H), 7.99 (s, 1H), 7.65 - 7.48 (m, 3H), 7.46 - 7.36 (m, 1H), 6.55 (d, J = 3.2 Hz, 1H), 3.14 (q, 2H), 2.11 (s, 3H), 1.29 (t, 3H).
MS(ESI+) m/z 377 (M+H)+
실시예 711: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)이소부티르아미드 (N-(4-(4-( ethylsulfonamido )-3- fluorophenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)isobutyramide)의 합성
Figure pat00815
1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 10.28 (s, 1H), 9.83 (s, 1H), 8.04 (s, 1H), 7.58 (d, J = 8.1 Hz, 3H), 7.49 - 7.38 (m, 1H), 6.63 - 6.50 (m, 1H), 3.18 (q, J = 7.2 Hz, 2H), 2.85 - 2.71 (m, 1H), 1.29 (t, J = 7.0 Hz, 3H), 1.10 (d, J = 6.7 Hz, 6H).
MS(ESI+) m/z 405 (M+H)+
실시예 712: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)부티르아미드 (N-(4-(4-( ethylsulfonamido )-3- fluorophenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)butyramide)의 합성
Figure pat00816
1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.29 (s, 1H), 8.02 (s, 1H), 7.70 - 7.51 (m, 3H), 7.45 - 7.37 (m, 1H), 6.56 (d, J = 3.4 Hz, 1H), 2.37 (q, J = 6.9 Hz, 2H), 1.62 (q, J = 7.5 Hz, 2H), 1.34 - 1.26 (m, 5H), 0.92 (t, J = 7.3 Hz, 3H).
MS(ESI+) m/z 405 (M+H)+
실시예 713: N-(4-(6-(( 시클로프로필메틸 )아미노)-1H- 피롤로[2,3-b]피리딘 -4-일)-2-플루오로 페닐) 에탄술폰아미드 (N-(4-(6-(( cyclopropylmethyl ) amino )-1H-pyrrolo[2,3-b]pyridin-4-yl)-2-fluorophenyl)ethanesulfonamide)의 합성
Figure pat00817
MS(ESI+) m/z 389 (M+H)+
실시예 714: (Z)-N-(4-(4-( 에틸설폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)-N'-메틸시클로프로판 카르복시미다미드 ((Z)-N-(4-(4-(ethylsulfonamido)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-N'-methylcyclopropanecarboximidamide)의 합성
Figure pat00818
MS(ESI+) m/z 398 (M+H)+
실시예 715: N-(4-(4-( 에틸술폰아미도 )페닐)-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판 카르보티오아미드 (N-(4-(4-( ethylsulfonamido ) phenyl )-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarbothioamide)의 합성
Figure pat00819
MS(ESI+) m/z 401 (M+H)+
실시예 716: N-(4-(4-( 에틸술폰아미도 )-3- 플루오로페닐 )-1H- 피롤로[2,3-b]피리딘 -6-일)시클로프로판 술폰아미드 (N-(4-(4-( ethylsulfonamido )-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanesulfonamide)의 합성
Figure pat00820
1H NMR (400 MHz, Chloroform-d) δ 10.37 (s, 1H), 7.77 (t, J = 8.3 Hz, 1H), 7.65 - 7.47 (m, 3H), 7.44 - 7.31 (m, 1H), 6.79 (s, 1H), 6.70 - 6.57 (m, 1H), 3.23 (q, J = 7.3 Hz, 2H), 2.65 (tt, J = 8.3, 4.7 Hz, 1H), 1.45 (t, J = 7.4 Hz, 3H), 0.99 (dt, J = 7.8, 3.7 Hz, 4H).
MS(ESI+) m/z 439 (M+H)+
실시예 717: 1 - 시클로프로필 -3-(4-(4-((1,1- 디옥시도티오모르폴리노 ) 메틸 )페닐)-1H-피롤로[2,3-b]피리딘-6-일)우레아 (1- cyclopropyl -3-(4-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)urea)의 합성
Figure pat00821
MS(ESI+) m/z 440 (M+H)+
실시예 718: N-(4-(2-(디메틸아미노)-7H- 피롤로[2,3-d]피리미딘 -4-일)페닐)-3,4-디플루오로벤젠술폰아미드 (N-(4-(2-( dimethylamino )-7H- pyrrolo[2,3- d]pyrimidin-4-yl)phenyl)-3,4-difluorobenzenesulfonamide)의 합성
Figure pat00822
1H NMR (400 MHz, Methanol-d4) δ 8.09 - 8.02 (m, 2H), 7.77 (ddd, J = 2.3, 7.3, 9.7 Hz, 1H), 7.66 (ddt, J = 1.8, 3.9, 8.6 Hz, 1H), 7.42 (ddd, J = 7.6, 8.7, 10.1 Hz, 1H), 7.32 - 7.25 (m, 2H), 7.02 (d, J = 3.6 Hz, 1H), 6.56 (d, J = 3.7 Hz, 1H), 3.23 (s, 6H).
MS(ESI+) m/z 430 (M+H)+
실시예 719: N-(2- 플루오로 -4-(2-( 페닐아미노 )-7H- 피롤로[2,3-d]피리미딘 -4-일)페닐)에탄술폰아미드 (N-(2- fluoro -4-(2-( phenylamino )-7H- pyrrolo[2,3- d]pyrimidin-4-yl)phenyl)ethanesulfonamide)의 합성
Figure pat00823
1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 9.93 (s, 1H), 9.30 (s, 1H), 8.04 - 7.95 (m, 2H), 7.93 - 7.84 (m, 2H), 7.62 (t, J = 8.5 Hz, 1H), 7.29 (ddd, J = 1.8, 5.4, 8.5 Hz, 3H), 6.90 (dd, J = 6.8, 8.0 Hz, 1H), 6.75 (dd, J = 1.8, 3.7 Hz, 1H), 3.18 (q, J = 7.3 Hz, 2H), 1.28 (t, J = 7.3 Hz, 3H).
MS(ESI+) m/z 412 (M+H)+
실시예 720: N-(4-(2-( 페닐아미노 )-7H- 피롤로[2,3-d]피리미딘 -4-일)페닐)에탄 술폰아미드 (N-(4-(2-( phenylamino )-7H- pyrrolo[2,3-d]pyrimidin -4-yl)phenyl)ethanesulfonamide)의 합성
Figure pat00824
MS(ESI+) m/z 394 (M+H)+
실시예 721: 3 -옥소-3-(3-(2-( 페닐아미노 )-7H- 피롤로[2,3-d]피리미딘 -4-일)-3,8-디아자비시클로[3.2.1]옥탄-8-일)프로판니트릴 (3-oxo-3-(3-(2-(phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)propanenitrile)의 합성
Figure pat00825
MS(ESI+) m/z 388 (M+H)+
시험예 1: 화학식 1화합물의 JAK1 활성 억제능 분석 (ADP- Glo TM Kinase assay)
본 발명에 따른 화합물의 JAK 억제 효능을 아래와 같이 확인하였다.
DMSO를 이용하여 대조물질과 시험물질을 농도별로 희석하여 준비하였다. 동시에 ATP (250 uM)와 JAK의 substrate (JAK1, IRS-1tide 40 ng/mL)를 kinase buffer (40 mM Tris-HCl pH 7.5, 20 mM MgCl2, 0.5mg/mL BSA, 50 uM DTT)에 희석하여 준비하였다.
Eppendorf tube에서 각 농도 별 시험약물, Substrate, ATP와 JAK enzyme을 혼합 후 40분간 30 oC, incubator에서 반응시켰다.
ADP-GloTM Kinase Enzyme System (Promega, USA, V9571)에 포함된 ADP-Glo™ reagent를 각 eppendorf tube에 가한 후 30 oC incubator에서 40분간 반응시켰다.
ADP-GloTM Kinase Enzyme System에 포함된 kinase detection reagent를 eppendorf tube에 넣은 후, Wallac Victor 2TM을 이용하여 integration time은 1초로 하고, luminescence를 측정하여 시험물질의 JAKs 인산화 저해능을 분석하였다. 대조군 대비 50%의 JAK 효소 활성 억제가 일어나는 화합물의 농도를 억제제의 IC50(nM)으로 결정하고, 그 결과를 아래 표1에 나타내었다.
[표 1]
Figure pat00826
Figure pat00827

Claims (8)

  1. 하기 화학식 1로 표시되는 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염:
    [화학식 1]
    Figure pat00828

    상기 식에서,
    X 는 C-A3 또는 N 이고,
    Y 는 C-A4 또는 N 이고,
    Z 는 N 또는 N-O 이고,
    A1 내지 A4 는 각각 독립적으로 H 또는 C1-C6알킬, C1-C6알콕시, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, C(=O)-OH, C(=O)-O-C1-C6알킬, S(=O)2-C1-C6알킬, 아릴 또는 헤테로아릴이고,
    B1 은 -(CH2)m-, -C(=O)-, -C(=S)-, -C(=NR1)-, -C(=O)-NR1-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -(CH2)m-의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있음},
    B2는 H, C1-C6알킬, C3-C7시클로알킬, 5-6원 헤테로시클로알킬, 아릴, 헤테로아릴, C1-C6알킬-아릴 또는 C1-C6알킬-헤테로아릴이고 {여기서, C3-C7시클로알킬, 5-6원 헤테로시클로알킬, 아릴, 헤테로아릴, C1-C6알킬-아릴 또는 C1-C6알킬-헤테로아릴의 하나 이상의 H는 C1-C6알킬, 히드록시 또는 할로겐으로 치환될 수 있음},
    B3 는 H 또는 C1-C6알킬이고,
    Cyclic linker는 C3-C7시클로알킬, C3-C7시클로알케닐, 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고,
    C1 및 C2는 각각 독립적으로 H, C1-C6알킬, C1-C6알콕시, C1-C6히드록시알킬, C1-C6시아노알킬, C1-C6할로알킬, 히드록시, 시아노, 할로겐, C(=O)-OH, C(=O)-O-C1-C6알킬, S(=O)2-C1-C6알킬, 아릴 또는 헤테로아릴이고,
    또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리 또는 스파이로 고리를 만들 수 있고,
    D1 은 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
    Figure pat00829
    ,
    Figure pat00830
    또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있고,
    Figure pat00831
    또는
    Figure pat00832
    의 하나 이상의 H는 C1-C6알킬, C1-C6히드록시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬로 치환될 수 있음},
    D2 는 -C(=O)-, -C(=O)-CH2-C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -C(=O)-CH2-C(=O)- 의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
    D3 는 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
    Figure pat00833
    또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있음},
    D4 는 H, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, S(=O)2-C1-C6알킬, C3-C7시클로알킬,
    Figure pat00834
    , 아릴 또는 헤테로아릴이고
    {여기서, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
    C3-C7시클로알킬 또는
    Figure pat00835
    의 하나 이상의 H는 C1-C6알킬, C1-C6할로알킬, C1-C6시아노알킬, 시아노, 할로겐, -C(=O)-R4 또는 -C(=O)-O-R4 로 치환될 수 있고,
    아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, C1-C6알콕시, C1-C6할로알킬, C1-C6히드록시알킬, C1-C6시아노알킬, C1-C6티오알킬, 히드록시, 시아노, 니트로, 할로겐, -C(=O)-R4, -C(=O)-NR1-R4, -S(=O)2-R4, -S(=O)2-NR1-R4, -NR1-R5,
    Figure pat00836
    , 아릴 또는 헤테로아릴로 치환될 수 있음 [이때,
    Figure pat00837
    의 하나 이상의 H는 C1-C6알킬 또는 (=O) 로 치환될 수 있음]},
    R1 및 R2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
    R3 는 H, C1-C6알킬, -C(=O)-R4, -C(=O)-O-R4, -S(=O)2-R4 또는 -S(=O)2-NR1-R4 이고 {여기서, W 가 -O-, -C(=O)- 또는 -S(=O)2- 인 경우 R3 는 아무 것도 아님 (null)},
    R4 는 H, C1-C6알킬 또는 C1-C6할로알킬이고,
    R5 는 H, C1-C6알킬,
    Figure pat00838
    , 아릴 또는 헤테로아릴이고 {여기서,
    Figure pat00839
    의 하나 이상의 H는 C1-C6알킬 또는 (=O) 로 치환될 수 있고, 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
    V 는 -CH- 또는 -N- 이고,
    W 는 -CH-, -N-, -O-, -S-, -C(=O)-, -S(=O)- 또는 -S(=O)2- 이고 {여기서, V 가 -CH- 인 경우 W 는 -CH- 가 아님},
    a 내지 d 는 각각 독립적으로 1, 2 또는 3 이고,
    m 은 1, 2 또는 3 이다.
  2. 제 1 항에 있어서,
    X 는 C-A3 또는 N 이고,
    Y 는 C-A4 또는 N 이고,
    Z 는 N 또는 N-O 이고,
    A1 내지 A4 는 각각 독립적으로 H 또는 C1-C6알킬 또는 C1-C6시아노알킬 이고,
    B1 은 -(CH2)m-, -C(=O)-, -C(=S)-, -C(=NR1)-, -C(=O)-NR1-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -(CH2)m-의 하나 이상의 H는 C1-C6알킬, 할로겐 또는 시아노로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있음},
    B2는 H, C1-C6알킬, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴이고 {여기서, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    B3 는 H 또는 C1-C6알킬이고,
    Cyclic linker는 C3-C7시클로알킬, C3-C7시클로알케닐, 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고,
    C1 및 C2는 각각 독립적으로 H, C1-C6알킬, C1-C6할로알킬, 히드록시, 시아노, 할로겐, C(=O)-OH, C(=O)-O-C1-C6알킬 또는 아릴이고,
    또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리 또는 스파이로 고리를 만들 수 있고,
    D1 은 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
    Figure pat00840
    ,
    Figure pat00841
    또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있고,
    Figure pat00842
    ,
    Figure pat00843
    또는
    Figure pat00844
    의 하나 이상의 H는 C1-C6알킬 또는 C1-C6시아노알킬로 치환될 수 있음},
    D2 는 -C(=O)-, -C(=O)-CH2-C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -C(=O)-CH2-C(=O)- 의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    D3 는 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
    Figure pat00845
    또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 시아노로 치환될 수 있음},
    D4 는 H, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, S(=O)2-C1-C6알킬, C3-C7시클로알킬,
    Figure pat00846
    , 아릴 또는 헤테로아릴이고
    {여기서, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6히드록시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
    C3-C7시클로알킬 또는
    Figure pat00847
    의 하나 이상의 H는 C1-C6알킬, C1-C6할로알킬, C1-C6시아노알킬, 시아노, 할로겐 또는 -C(=O)-O-R4 로 치환될 수 있고,
    아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, C1-C6알콕시, C1-C6할로알킬, C1-C6티오알킬, 히드록시, 시아노, 니트로, 할로겐, -C(=O)-R4, -C(=O)-NR1-R4, -S(=O)2-R4, -S(=O)2-NR1-R4, -NR1-R5 또는
    Figure pat00848
    로 치환될 수 있음 [이때,
    Figure pat00849
    의 하나 이상의 H는 (=O) 로 치환될 수 있음]},
    R1 및 R2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
    R3 는 H, C1-C6알킬, -C(=O)-R4, -C(=O)-O-R4, -S(=O)2-R4 또는 -S(=O)2-NR1-R4 이고 {여기서, W 가 -O-, -C(=O)- 또는 -S(=O)2- 인 경우 R3 는 아무 것도 아님 (null)},
    R4 는 H, C1-C6알킬 또는 C1-C6할로알킬이고,
    R5 는 H,
    Figure pat00850
    또는 아릴이고 {여기서,
    Figure pat00851
    의 하나 이상의 H는 (=O) 로 치환될 수 있고, 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
    V 는 -CH- 또는 -N- 이고,
    W 는 -CH-, -N-, -O-, -S-, -C(=O)-, -S(=O)- 또는 -S(=O)2- 이고 {여기서, V 가 -CH- 인 경우 W 는 -CH- 가 아님},
    a 내지 d 는 각각 독립적으로 1, 2 또는 3 이고,
    m 은 1 또는 2 인,
    화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염.
  3. 제 2 항에 있어서,
    X 는 C-A3 이고,
    Y 는 C-A4 이고,
    Z 는 N 또는 N-O 이고,
    A1 내지 A4 는 각각 독립적으로 H 또는 C1-C6알킬 또는 C1-C6시아노알킬 이고,
    B1 은 -(CH2)m-, -C(=O)-, -C(=S)-, -C(=NR1)-, -C(=O)-NR1-, -S(=O)2- 또는 아무 것도 아니고 (null),
    B2는 H, C1-C6알킬, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴이고 {여기서, C3-C7시클로알킬, 아릴, 헤테로아릴 또는 C1-C6알킬-아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    B3 는 H이고,
    Cyclic linker는 C3-C7시클로알킬, C3-C7시클로알케닐, 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고,
    C1 및 C2는 각각 독립적으로 H, C1-C6알킬, C1-C6할로알킬, 히드록시, 시아노, 할로겐, C(=O)-OH, C(=O)-O-C1-C6알킬, 또는 아릴이고,
    또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리 또는 스파이로 고리를 만들 수 있고,
    D1 은 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
    Figure pat00852
    ,
    Figure pat00853
    또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있고, 또는 하나 이상의 탄소 원자와 함께 서로 연결되어 고리를 형성할 수 있고,
    Figure pat00854
    ,
    Figure pat00855
    또는
    Figure pat00856
    의 하나 이상의 H는 C1-C6알킬 또는 C1-C6시아노알킬로 치환될 수 있음},
    D2 는 -C(=O)-, -C(=O)-CH2-C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null) {여기서, -C(=O)-CH2-C(=O)- 의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    D3 는 -(CH2)m-, -(CH2)m-NR1-, -NR1-, -O-,
    Figure pat00857
    또는 아무 것도 아니고 (null) {여기서, -(CH2)m- 또는 -(CH2)m-NR1- 의 하나 이상의 H는 시아노로 치환될 수 있음},
    D4 는 H, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6할로알킬, C1-C6시아노알킬, S(=O)2-C1-C6알킬, C3-C7시클로알킬,
    Figure pat00858
    , 아릴 또는 헤테로아릴이고
    {여기서, C1-C6알킬, C1-C6알케닐, C1-C6알콕시알킬, C1-C6할로알킬 또는 C1-C6시아노알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
    C3-C7시클로알킬 또는
    Figure pat00859
    의 하나 이상의 H는 C1-C6알킬, C1-C6할로알킬, C1-C6시아노알킬, 시아노, 할로겐 또는 -C(=O)-O-R4 로 치환될 수 있고,
    아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, C1-C6알콕시, C1-C6할로알킬, C1-C6티오알킬, 히드록시, 시아노, 니트로, 할로겐, -C(=O)-R4, -C(=O)-NR1-R4, -S(=O)2-R4, -S(=O)2-NR1-R4, -NR1-R5 또는
    Figure pat00860
    로 치환될 수 있음 [이때,
    Figure pat00861
    의 하나 이상의 H는 (=O) 로 치환될 수 있음]},
    R1 및 R2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
    R3 는 H, C1-C6알킬, -C(=O)-R4, -C(=O)-O-R4, -S(=O)2-R4 또는 -S(=O)2-NR1-R4 이고 {여기서, W 가 -O-, -C(=O)- 또는 -S(=O)2- 인 경우 R3 는 아무 것도 아님 (null)},
    R4 는 H, C1-C6알킬 또는 C1-C6할로알킬이고,
    R5 는 H,
    Figure pat00862
    또는 아릴이고 {여기서,
    Figure pat00863
    의 하나 이상의 H는 (=O) 로 치환될 수 있고, 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬 또는 할로겐으로 치환될 수 있음},
    V 는 -CH- 또는 -N- 이고,
    W 는 -CH-, -N-, -O-, -S-, -C(=O)-, -S(=O)- 또는 -S(=O)2- 이고 {여기서, V 가 -CH- 인 경우 W 는 -CH- 가 아님},
    a 내지 d 는 각각 독립적으로 1, 2 또는 3 이고,
    m 은 1 또는 2 인,
    화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염.
  4. 제 1 항에 있어서,
    X 는 C-A3 이고,
    Y 는 N 이고,
    Z 는 N 이고,
    A1 내지 A3 는 각각 독립적으로 H 또는 C1-C6알킬이고,
    B1 은 -C(=O)- 이고,
    B2는 C3-C7시클로알킬 또는 아릴이고 {여기서, C3-C7시클로알킬 또는 아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    B3 는 H 또는 C1-C6알킬이고,
    Cyclic linker는 5-6원 헤테로시클로알킬, 5-6원 헤테로시클로알케닐, 아릴 또는 헤테로아릴이고
    C1 및 C2는 각각 독립적으로 H, C1-C6알킬 또는 할로겐이고,
    또는 C1 및 C2는 하나 이상의 탄소 원자를 통해 서로 연결되어 바이시클릭 고리를 만들 수 있고,
    D1 은 -(CH2)m-, -NR1- 또는 아무 것도 아니고 (null),
    D2 는 -C(=O)-, -C(=S)-, -S(=O)2- 또는 아무 것도 아니고 (null),
    D3 는 -(CH2)m-, -NR1-, -O- 또는 아무 것도 아니고 (null),
    D4 는 C1-C6알킬, C1-C6알케닐, C1-C6히드록시알킬, C1-C6할로알킬, C1-C6시아노알킬, C3-C7시클로알킬,
    Figure pat00864
    , 아릴 또는 헤테로아릴이고
    {여기서, C3-C7시클로알킬 또는
    Figure pat00865
    의 하나 이상의 H는 C1-C6알킬 또는 시아노로 치환될 수 있고,
    아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6알킬, 시아노, 할로겐 또는 -C(=O)-NR1-R4 로 치환될 수 있음},
    R1 은 H 또는 C1-C6알킬이고,
    R4 는 H이고,
    V 는 -CH- 또는 -N- 이고,
    W 는 -O- 또는 -S(=O)2- 이고,
    a 및 b 는 각각 독립적으로 1, 2 또는 3 이고,
    m 은 1 또는 2 인,
    화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염.
  5. 제 2 항에 있어서,
    X 는 N 이고,
    Y 는 C-A4 이고,
    Z 는 N 이고,
    A1, A2 및 A4 는 각각 독립적으로 H 또는 C1-C6알킬이고,
    B1 은 -C(=O)- 이고,
    B2는 C3-C7시클로알킬이고 {여기서, C3-C7시클로알킬의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    B3 는 H 이고,
    Cyclic linker는 아릴이고
    C1 및 C2는 각각 독립적으로 H, C1-C6알킬 또는 할로겐이고,
    D1 은 -(CH2)m- 또는 -NR1-,
    D2 는 -S(=O)2- 또는 아무 것도 아니고 (null),
    D3 는 아무 것도 아니고 (null),
    D4 는 C1-C6알킬, C1-C6할로알킬 또는 헤테로아릴이고
    {여기서, C1-C6알킬 또는 C1-C6할로알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
    헤테로아릴의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    R1 은 H 이고,
    m 은 1 또는 2 인,
    화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염.
  6. 제 2 항에 있어서,
    X 는 N 이고,
    Y 는 N 이고,
    Z 는 N 이고,
    A1 및 A2 는 각각 독립적으로 H 또는 C1-C6알킬이고,
    B1 은 -C(=O)- 이고,
    B2는 C3-C7시클로알킬이고 {여기서, C3-C7시클로알킬의 하나 이상의 H는 C1-C6알킬로 치환될 수 있음},
    B3 는 H 이고,
    Cyclic linker는 아릴이고
    C1 및 C2는 각각 독립적으로 H, C1-C6알킬 또는 할로겐이고,
    D1 은 -(CH2)m, -NR1-, -NR1- 또는 -O- 이고,
    D2 는 -S(=O)2- 또는 아무 것도 아니고 (null),
    D3 는 아무 것도 아니고 (null),
    D4 는 C1-C6알킬, C1-C6할로알킬,
    Figure pat00866
    , 아릴 또는 헤테로아릴이고
    {여기서, C1-C6알킬 또는 C1-C6할로알킬의 하나 이상의 H는 C3-C7시클로알킬로 치환될 수 있고,
    아릴 또는 헤테로아릴의 하나 이상의 H는 시아노 또는 할로겐로 치환될 수 있음},
    R1 은 H 이고,
    V 는 -N- 이고,
    W 는 -O- 또는 -S(=O)2- 이고,
    a 및 b 는 각각 독립적으로 1, 2 또는 3 이고,
    m 은 1 또는 2 인,
    화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염.
  7. 제 1 항에 있어서, 하기 화합물들로 이루어진 군으로부터 선택된 어느 하나인 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염:
    Figure pat00867

    Figure pat00868

    Figure pat00869

    Figure pat00870

    Figure pat00871

    Figure pat00872

    Figure pat00873

    Figure pat00874

    Figure pat00875

    Figure pat00876

    Figure pat00877

    Figure pat00878

    Figure pat00879

    Figure pat00880

    Figure pat00881

    Figure pat00882

    Figure pat00883

    Figure pat00884

    Figure pat00885

    Figure pat00886

    Figure pat00887

    Figure pat00888

    Figure pat00889

    Figure pat00890

    Figure pat00891

    Figure pat00892

    Figure pat00893

    Figure pat00894

    Figure pat00895

    Figure pat00896

    Figure pat00897

    Figure pat00898

    Figure pat00899

    Figure pat00900

    Figure pat00901

    Figure pat00902

    Figure pat00903

    Figure pat00904

    Figure pat00905

    Figure pat00906

    Figure pat00907

    Figure pat00908

    Figure pat00909

    Figure pat00910

    Figure pat00911

    Figure pat00912

    Figure pat00913

    Figure pat00914
  8. 제 1 항 내지 제 7 항 중 어느 하나의 항의 화합물, 이의 입체이성질체 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 암, 자가면역질환, 신경질환, 대사질환 또는 감염의 예방 또는 치료용 약학적 조성물.


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AU2018353759A1 (en) 2020-06-04
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