ES2608780T3 - Nuevo proceso para la preparación de intermediarios útiles para la elaboración de inhibidores de NEP - Google Patents

Nuevo proceso para la preparación de intermediarios útiles para la elaboración de inhibidores de NEP Download PDF

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ES2608780T3
ES2608780T3 ES11758422.7T ES11758422T ES2608780T3 ES 2608780 T3 ES2608780 T3 ES 2608780T3 ES 11758422 T ES11758422 T ES 11758422T ES 2608780 T3 ES2608780 T3 ES 2608780T3
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co2h
boc
solvent
transition metal
metal catalyst
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David Hook
Bernhard Riss
Jianguang Zhou
Yunzhong Li
Erhard Bappert
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Novartis AG
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    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract

Un proceso para la preparación de un compuesto de la fórmula (4), o de una sal del mismo:**Fórmula** en donde: R1 es hidrógeno o un grupo protector de nitrógeno; comprendiendo este proceso: A) hacer reaccionar un compuesto de la fórmula (1), o una sal del mismo:**Fórmula** en donde R1 es hidrógeno o un grupo protector de nitrógeno; con un catalizador de metal de transición, opcionalmente en la presencia de una base, para obtener el compuesto de la fórmula (4), o una sal del mismo, o B) hacer reaccionar un compuesto de la fórmula (3), o una sal del mismo**Fórmula** en donde: R1 es hidrógeno o un grupo protector de nitrógeno; con un seleniuro en presencia de una base para obtener un compuesto de fórmula (6) o una sal del mismo,

Description

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Tabla del Ejemplo 5
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
1
1
A-3 1.20 25 0.042 S-2 - - 0.5 84
2
1 - A-3 L-7 1.20 25 0.042 S-3 - - 0.5 84
3
1 - A-3 L-24 1.20 25 0.042 S-3 - - 0.5 84
4
1 - A-3 L-9 1.20 25 0.042 S-3 - - 0.5 84
5
1 - A-2 L-1 1.20 25 0.042 S-2 - - 0.5 84
6
1 - A-3 L-22 1.20 25 0.042 S-3 - - 0.5 84
7
1 - A-3 L-30 1.20 25 0.042 S-2 - - 0.5 84
8
1 - A-2 L-21 1.20 25 0.042 S-2 - - 0.5 84
9
1 - A-3 L-21 1.20 25 0.042 S-2 - - 0.5 84
10
1 - A-2 L-5 1.20 25 0.042 S-2 - - 0.5 84
32
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
11
1 - A-1 L-10 1.20 25 0.042 S-3 - - 0.5 84
12
3 - A-2 L-13 1.05 100 0.5 S-3 10 5 15 33
13
1 - A-2 L-3 1.20 25 0.042 S-2 - - 0.5 84
14
1 - A-3 L-28 1.20 25 0.042 S-3 - - 0.5 84
15
1 - A-1 L-18 1.20 25 0.042 S-3 - - 0.5 84
16
1 - A-3 L-30 1.20 25 0.042 S-3 - - 0.5 84
17
1 - A-3 L-10 1.20 25 0.042 S-2 - - 0.5 84
18
1 - A-2 L-2 1.20 25 0.042 S-2 - - 0.5 84
19
1 - A-1 L-17 1.20 25 0.042 S-3 - - 0.5 84
33
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
20
1 - A-2 L-14 1.20 25 0.042 S-2 - - 0.5 84
21
1 - A-2 L-27 1.20 25 0.042 S-2 - - 0.5 84
22
1 - A-2 L-15 1.20 25 0.042 S-2 - - 0.5 84
23
1 - A-1 L-8 1.20 25 0.042 S-3 - - 0.5 84
24
2 C-2 - - 1.20 25 0.042 S-3 - - 0.5 84
25
1 - A-3 L-20 1.20 25 0.042 S-3 - - 0.5 84
26
1 - A-3 L-26 1.20 25 0.042 S-2 - - 0.5 84
27
1 - A-3 L-11 1.20 25 0.042 S-2 - - 0.5 84
28
1 - A-3 L-5 1.20 25 0.042 S-3 - - 0.5 84
34
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
29
1 - A-2 L-13 1.20 25 0.042 S-2 - - 0.5 84
30
1 - A-3 L-25 1.20 25 0.042 S-2 - - 0.5 84
31
1 - A-2 L-6 1.20 25 0.042 S-2 - - 0.5 84
32
1 - A-2 L-31 1.20 25 0.042 S-2 - - 0.5 84
33
1 - A-3 L-20 1.20 25 0.042 S-2 - - 0.5 84
34
1 - A-3 L-24 1.20 25 0.042 S-2 - - 0.5 84
35
2 C-3 - - 1.20 25 0.042 S-2 - - 0.5 84
36
1 - A-2 L-18 1.20 25 0.042 S-2 - - 0.5 84
37
1 - A-1 L-15 1.20 25 0.042 S-3 - - 0.5 84
35
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
38
1 - A-1 L-23 1.20 25 0.042 S-3 - - 0.5 84
39
1 - A-3 L-26 1.20 25 0.042 S-3 - - 0.5 84
40
1 - A-1 L-29 1.20 25 0.042 S-3 - - 0.5 84
41
1 - A-2 L-29 1.20 25 0.042 S-2 - - 0.5 84
42
1 - A-3 L-11 1.20 25 0.042 S-3 - - 0.5 84
43
1 - A-3 L-3 1.20 25 0.042 S-2 - - 0.5 84
44
1 - A-3 L-27 1.20 25 0.042 S-2 - - 0.5 84
45
1 - A-2 L-23 1.20 25 0.042 S-2 - - 0.5 84
46
1 - A-2 L-17 1.20 25 0.042 S-2 - - 0.5 84
36
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
47
1 - A-2 L-4 1.20 25 0.042 S-2 - - 0.5 84
48
1 - A-3 L-17 1.20 25 0.042 S-2 - - 0.5 84
49
1 - A-1 L-1 1.20 25 0.042 S-3 - - 0.5 84
50
1 - A-3 L-25 1.20 25 0.042 S-3 - - 0.5 84
51
1 - A-2 L-16 1.20 25 0.042 S-2 - - 0.5 84
52
1 - A-2 L-26 1.20 25 0.042 S-2 - - 0.5 84
53
1 - A-3 L-14 1.20 25 0.042 S-3 - - 0.5 84
54
1 - A-2 L-12 1.20 25 0.042 S-2 - - 0.5 84
55
1 - A-3 L-4 1.20 25 0.042 S-2 - - 0.5 84
37
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
56
1 - A-3 L-29 1.20 25 0.042 S-2 - - 0.5 84
57
2 C-1 - - 1.20 25 0.042 S-3 - - 0.5 84
58
1 - A-3 L-23 1.20 25 0.042 S-2 - - 0.5 84
59
1 - A-3 L-19 1.20 25 0.042 S-2 - - 0.5 84
60
1 - A-1 L-4 1.20 25 0.042 S-3 - - 0.5 84
61
1 - A-2 L-11 1.20 25 0.042 S-2 - - 0.5 84
62
1 - A-3 L-2 1.20 25 0.042 S-2 - - 0.5 84
63
1 - A-3 L-14 1.20 25 0.042 S-2 - - 0.5 84
64
1 - A-2 L-22 1.20 25 0.042 S-2 - - 0.5 84
38
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
65
1 - A-3 L-5 1.20 25 0.042 S-2 - - 0.5 84
66
1 - A-3 L-13 1.20 25 0.042 S-2 - - 0.5 84
67
1 - A-2 L-19 1.20 25 0.042 S-2 - - 0.5 84
68
1 - A-3 L-31 1.20 25 0.042 S-2 - - 0.5 84
69
1 - A-2 L-9 1.20 25 0.042 S-2 - - 0.5 84
70
1 - A-3 L-9 1.20 25 0.042 S-2 - - 0.5 84
71
1 - A-2 L-30 1.20 25 0.042 S-2 - - 0.5 84
72
1 - A-1 L-19 1.20 25 0.042 S-3 - - 0.5 84
73
1 - A-3 L-15 1.20 25 0.042 S-2 - - 0.5 84
39
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
74
3 - A-2 L-13 1.05 25 0.5 S-3 10 5 15 33
75
3 - A-2 L-13 1.05 25 0.5 S-2 10 5 15 33
76
3 - A-4 L-26 1.05 25 0.26 S-1 10 5 15 17
77
1 - A-3 L-6 1.20 25 0.042 S-2 - - 0.5 84
78
2 C-2 - - 1.20 25 0.042 S-2 - - 0.5 84
79
1 - A-3 L-3 1.20 25 0.042 S-3 - - 0.5 84
80
1 - A-3 L-22 1.20 25 0.042 S-2 - - 0.5 84
81
1 - A-3 L-12 1.20 25 0.042 S-2 - - 0.5 84
82
1 - A-2 L-8 1.20 25 0.042 S-2 - - 0.5 84
40
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
83
1 - A-3 L-8 1.20 25 0.042 S-2 - - 0.5 84
84
1 - A-3 L-7 1.20 25 0.042 S-2 - - 0.5
84
85
1 - A-2 L-25 1.20 25 0.042 S-2 - - 0.5 84
86
1 - A-3 L-1 1.20 25 0.042 S-2 - - 0.5 84
87
1 - A-2 L-7 1.20 25 0.042 S-2 - - 0.5 84
88
1 - A-2 L-20 1.20 25 0.042 S-2 - - 0.5 84
89
2 C-3 - - 1.20 25 0.042 S-3 - - 0.5 84
90
3 - A-4 L-25 1.05 25 0.26 S-1 10 5 15 17
91
1 - A-2 L-28 1.20 25 0.042 S-2 - - 0.5 84
41
Método
Procedimiento General Catalizador de metal de transición Proporción del ligando por átomo de metal dentro del complejoorganometálico Proporción del 5a (R1 = Boc, R2 = H, R3 = CO2H) al catalizador demetal de transición (proporción S/C) Cantidad del 5a (R1 = Boc, R2 = H, R3 = CO2H) (milimoles) Solvente (S) ml de solvente (5a, R1 = Boc, R2 = H, R3 = CO2H) Volumen de solvente (Catalizador de metal de transición) (ml) Volumen de solvente (Volumen de reacción total) (ml) Concentración del 5a (R1 = Boc, R2 = H, R3 = CO2H) (mM)
Catalizador Organometálico (C)
Complejo Organometálico (A) Ligando Quiral (L)
92
1 - A-1 L-16 1.20 25 0.042 S-3 - - 0.5 84
93
1 - A-3 L-16 1.20 25 0.042 S-2 - - 0.5 84
94
2 C-1 - - 1.20 25 0.042 S-2 - - 0.5 84
95
1 - A-2 L-10 1.20 25 0.042 S-2 - - 0.5 84
96
1 - A-3 L-18 1.20 25 0.042 S-2 - - 0.5 84
Para el propósito del Ejemplo 7, se aplican las siguientes abreviaturas: Catalizador organometálico (C) C-1 = [Rh(cod)-(SL-P005-1)]BF4 = [Rh(cod)-(L-32)]BF4 C-2 = [Rh(cod)-(SL-P114-1)]BF4 = [Rh(cod)-(L-33)]BF4 C-3 = [Rh(cod)-(SL-P102-1)]O3SCF3 = [Rh(cod)-(L-34)]O3SCF3 Complejo organometálico (A) A-1 = [Rh(cod)2]O3SCF3 A-2 = [Rh(nbd)2]BF4
42
imagen31
imagen32

Claims (1)

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WO2016074651A1 (en) 2014-11-14 2016-05-19 Zentiva, K.S. A method for the preparation, isolation and purification of pharmaceutically applicable forms of ahu-377
TW201632493A (zh) 2015-02-13 2016-09-16 諾華公司 新穎方法
WO2016135751A1 (en) 2015-02-25 2016-09-01 Mylan Laboratories Limited Novel process for the preparation of sacubitril and its intermediates
CN106146351B (zh) * 2015-04-03 2020-09-11 博瑞生物医药（苏州）股份有限公司 制备联芳基取代的4-氨基-丁酸或其衍生物的方法
CN104860894B (zh) * 2015-06-10 2017-05-17 北京博全健医药科技有限公司 一种抗心衰药lcz696的制备方法
CN106278932B (zh) * 2015-06-12 2020-10-09 上海交通大学 环状α-脱氢胺基酮、手性环状α-胺基酮及其制备方法
WO2017051326A1 (en) 2015-09-23 2017-03-30 Novartis Ag New processes and intermediates useful in synthesis of nep inhibitors
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EP3386945A1 (en) 2015-12-11 2018-10-17 Zentiva, K.S. Solid forms of (2r,4s)-5-(biphenyl-4-yl)-4-[(3-carboxypropionyl)amino]-2- -methylpentanoic acid ethyl ester, its salts and a preparation method
CN105924355B (zh) * 2016-05-11 2018-08-17 浙江宏元药业有限公司 沙库比曲中间体及沙库比曲中间体和沙库比曲的制备方法
WO2018007919A1 (en) 2016-07-05 2018-01-11 Novartis Ag New process for early sacubitril intermediates
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EP3421455B1 (en) * 2017-06-29 2019-03-27 F.I.S.- Fabbrica Italiana Sintetici S.p.A. Improved process for the preparation of chiral 3-amino-piperidins, useful intermediates for the preparation of tofacitinib
CN108084058A (zh) * 2017-12-15 2018-05-29 江苏中邦制药有限公司 一种lcz696中间体的制备方法
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Family Cites Families (9)

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DE60110516T2 (de) 2000-09-21 2005-10-13 Solvias Ag Phosphinite-oxazoline und Metallkomplexe
CN1238361C (zh) 2003-02-21 2006-01-25 南开大学 螺环双膦配体
US20050286512A1 (en) 2004-06-28 2005-12-29 Atul Mahamuni Flow processing
JP5090926B2 (ja) 2004-12-22 2012-12-05 ディーエスエム アイピー アセッツ ビー．ブイ． キラルイリジウム錯体を使用するアルケンの不斉水素化
EP1903027A1 (en) * 2006-09-13 2008-03-26 Novartis AG Process for preparing biaryl substituted 4-amino-butyric acid or derivatives thereof and their use in the production of NEP inhibitors
AR064842A1 (es) 2007-01-12 2009-04-29 Mazzucco Gavieiro Maria Belen Pirrolidin-2-onas, y su uso en la preparacion de inhibidores de nep
EP2148886B1 (en) * 2007-05-10 2014-02-19 R & D Biopharmaceuticals Gmbh Tubulysine derivatives
PE20091364A1 (es) 2008-01-17 2009-10-13 Novartis Ag Proceso para la preparacion de inhibidores de nep

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