CN114853662B - Process for preparing chiral hydrazinopiperidine derivatives - Google Patents

Process for preparing chiral hydrazinopiperidine derivatives Download PDF

Info

Publication number
CN114853662B
CN114853662B CN202210069453.4A CN202210069453A CN114853662B CN 114853662 B CN114853662 B CN 114853662B CN 202210069453 A CN202210069453 A CN 202210069453A CN 114853662 B CN114853662 B CN 114853662B
Authority
CN
China
Prior art keywords
compound
chiral
hydrazinopiperidine
hydrazine
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202210069453.4A
Other languages
Chinese (zh)
Other versions
CN114853662A (en
Inventor
刘凛威
韩桂芳
张洋
李建国
李晓迅
胡同军
王颖
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sichuan Qingmu Pharmaceutical Co ltd
Original Assignee
Sichuan Qingmu Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sichuan Qingmu Pharmaceutical Co ltd filed Critical Sichuan Qingmu Pharmaceutical Co ltd
Publication of CN114853662A publication Critical patent/CN114853662A/en
Application granted granted Critical
Publication of CN114853662B publication Critical patent/CN114853662B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/56—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

The invention belongs to the technical field of pharmaceutical chemistry synthesis, and particularly relates to a preparation method of chiral hydrazinopiperidine derivatives. Aiming at the problems of high material price, low yield of chiral intermediates obtained by a chemical resolution method, high toxicity of nitroso compounds and the like in the prior art, the application provides a method for obtaining a compound I by reacting a compound II with azodicarbonate; the compound I reacts with hydrazine compounds in an organic solvent to obtain chiral hydrazinopiperidine derivative compounds IV; the compound IV can be used for preparing ibrutinib. The method has the advantages of cheap and easily obtained synthetic raw materials, mild reaction conditions, high yield, high optical purity, safety and environmental protection, and is suitable for industrialized mass production.

Description

Process for preparing chiral hydrazinopiperidine derivatives
Technical Field
The invention belongs to the technical field of pharmaceutical chemistry synthesis, and particularly relates to a preparation method of chiral hydrazinopiperidine derivatives.
Background
Ibrutinib has the following structure, chemical name 1- [3 (R) -3- [ 4-amino-3- (4-phenoxyphenyl) -1H-pyrazolo [3,4-d ] pyrimidin-1-yl ] piperidin-1-yl ] -2-propen-1-one:
ibrutinib is an oral small molecule BTK inhibitor, and belongs to the first innovative medicine. The drug can be selectively and covalently combined with cysteine residues in the active center of target protein BTK, and can irreversibly inhibit the activity of the target protein BTK, so that proliferation and survival of malignant B cells can be effectively inhibited, and the drug is the first drug which is identified and batched by FDA breakthrough therapy.
The compound with the following formula is a chiral hydrazinopiperidine derivative for synthesizing ibrutinib:
the method disclosed in us patent WO2016115356A1 prepares ibrutinib from chiral hydrazinopiperidine derivatives of formula vii, expressed by the following equation:
chinese patent CN201710596824.3 discloses a process for preparing ibrutinib from chiral hydrazinopiperidine compounds of formula viii, represented by the following equation:
in conclusion, the chiral hydrazinopiperidine derivative is an important intermediate for synthesizing ibrutinib, has high synthesis value, and has important significance in developing a synthesis method of the compound.
At present, the method for synthesizing the chiral hydrazinopiperidine derivatives mainly comprises the following steps: racemic aminopiperidine is used as a starting material, and hydrazinopiperidine compounds VIII are obtained through chemical chiral resolution, boc protection, nitrosation and reduction, such as Chinese patents CN107383017, CN109180683 and CN107233344. The method has the defects that materials are expensive, chiral intermediates are obtained by using a chemical resolution method, the yield is low, and simultaneously nitroso compounds with high toxicity are used, so that the method is not suitable for industrial production.
Disclosure of Invention
Aiming at the problems existing in the prior art, the application provides a preparation method of chiral hydrazinopiperidine derivative compound IV. The preparation method of the chiral hydrazinopiperidine derivative compound IV is as follows:
the preparation process comprises the following steps:
step a:
reacting the compound II with azodicarbonate under the conditions of an organic solvent and a chiral small organic molecule catalyst to obtain a compound I;
step b:
the compound I reacts with hydrazine compounds under the condition of an organic solvent and alkali to obtain chiral hydrazinopiperidine derivatives IV.
The organic solvent in step a is selected from tetrahydrofuran, ethyl acetate, dichloromethane, 1, 2-dichloroethane or acetonitrile; preferably, the organic solvent in step a is tetrahydrofuran.
The chiral small organic molecule catalyst in the step a is selected from quinine or cinchonidine, D-proline or diphenyl prolinol trimethyl silyl ether; preferably, the chiral small organic molecule catalyst in step a is quinine.
The molar ratio of the compound II to the azodicarbonate in the step a is 1:0.9-2.0; preferably, the molar ratio of compound II to azodicarbonate in step a is from 1:1.0 to 1.5.
The reaction temperature in the step a is-10-40 ℃; preferably, the reaction temperature of step a is from 0 to 30 ℃.
The organic solvent in step b is independently selected from tetrahydrofuran, diglycol, triglycol, methanol, ethanol or acetonitrile; preferably, the organic solvent in step b is selected from the group consisting of diglycolide.
The base in step b is independently selected from potassium hydroxide, sodium borohydride or sodium cyanoborohydride; preferably, the base is potassium hydroxide.
The molar ratio of the alkali to the compound I in the step b is 1-4.0:1; preferably, the molar ratio of base to compound I is from 1 to 3.0:1.
the hydrazine compound in the step b is independently selected from hydrazine hydrate, p-toluenesulfonyl hydrazine or tert-butyl hydrazinoformate; preferably, the hydrazine compound is selected from hydrazine hydrate.
In the step b, the molar ratio of the hydrazine compound to the compound I is 1-8.0:1; preferably, the molar ratio of the hydrazine compound to the compound I is 1-4.0: 1.
the reaction temperature in the step b is 60-190 ℃; preferably, the reaction temperature of step b is 120 to 160 ℃.
Another object of the present invention is to disclose compound i having the structure:
the synthesis process uses cheap and easily available starting materials, the synthesis process steps are mild in reaction conditions, and the chiral hydrazinopiperidine derivative IV is obtained in high yield and high optical purity. Chiral hydrazinopiperidine derivatives IV can be used for preparing ibrutinib.
Detailed Description
The present invention is described in further detail below with reference to examples, but is not limited to the following examples, and any equivalents in the art, which are in accordance with the present disclosure, are intended to fall within the scope of the present invention.
Nuclear magnetic resonance (1 HNMR) displacement (δ) is given in parts per million (ppm); nuclear magnetic resonance (1 HNMR) was measured using a Bruker AVANCE-300 nuclear magnetic resonance apparatus using deuterated chloroform (CDCl 3-d 6) as the solvent, tetramethylsilane (TMS) as the internal standard, and chemical shifts were given in units of 10-6 (ppm).
In the examples, DEAD refers to diethyl azodicarboxylate.
In the examples DIAD refers to diisopropyl azodicarboxylate.
EXAMPLE 1 preparation of Compound I
2kg of Compound II was dissolved in 15L of tetrahydrofuran at 0℃and 1.7kg of DEAD (1.1 eq) and 0.6kg of quinine catalyst were added in this order, the reaction solution was stirred for 12 hours, the insoluble matter was filtered, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (3.2 kg, yield 85%, ee value 99.5%).
1 H-NMR(300MHz,DMSO-d6):δ11.21(s,1H),5.12(t,1H),4.14(q,4H),3.54(m,1H),3.30(m,3H),2.70(m,2H),1.42(s,9H),1.25(t,6H).EIMS m/z 374.1([M+H] + ).
EXAMPLE 2 preparation of Compound I
500g of Compound II was dissolved in 4L of tetrahydrofuran at 30℃and 353g of DEAD (0.9 eq) and 200g of quinine catalyst were added in this order, the reaction solution was stirred for 12h, the insoluble matter was filtered off, the filtrate was dried by spinning, and then recrystallized with ethyl acetate-petroleum ether to give pure Compound I (656 g, yield 70%, ee 98.8%). Nuclear magnetic and mass spectral data were consistent with example 1.
EXAMPLE 3 preparation of Compound I
300g of Compound II was dissolved in 2L of tetrahydrofuran at 5℃and 282g of DEAD (1.2 eq) and 120g of quinine catalyst were added in this order, the reaction solution was stirred for 12h, the insoluble matter was filtered off, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (507 g, yield 90%, ee value 99.1%). Nuclear magnetic and mass spectral data were consistent with example 1.
EXAMPLE 4 preparation of Compound I
600g of Compound II was dissolved in 4L of methylene chloride at 10℃and 611g of DEAD (1.3 eq) and 240g of quinine catalyst were added in this order, the reaction solution was stirred for 12 hours, the insoluble matter was filtered off, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (967 g, yield 86%, ee value 98.5%). Nuclear magnetic and mass spectral data were consistent with example 1.
EXAMPLE 5 preparation of Compound I
800g of Compound II was dissolved in 5L of ethyl acetate at 15℃and 877g of DEAD (1.3 eq) and 320g of quinine catalyst were added in this order, the reaction solution was stirred for 12h, the insoluble matter was filtered off, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (1364 g, yield 91%, ee value 98.2%). Nuclear magnetic and mass spectral data were consistent with example 1.
EXAMPLE 6 preparation of Compound I
700g of Compound II was dissolved in 4L of tetrahydrofuran at 20℃and 857g of DEAD (1.4 eq) and 343g of diphenylprolyl trimethylsilyl ether catalyst were added in this order, the reaction solution was stirred for 12 hours, insoluble matter was filtered, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (1207 g, yield 86%, ee value 99.6%). Nuclear magnetic and mass spectral data were consistent with example 1.
EXAMPLE 7 preparation of Compound I
200g of Compound II was dissolved in 2L of tetrahydrofuran at 15℃and 304.5g of DIAD (1.5 eq) and 59g of cinchonidine catalyst were added in this order, the reaction solution was stirred for 12 hours, the insoluble matter was filtered off, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (322 g, yield 80%, ee value 98.9%).
1 H-NMR(300MHz,DMSO-d6):δ11.22(s,1H),5.06(t,1H),4.72(m,2H),3.56(m,1H),3.28(m,3H),2.68(m,2H),1.45(s,9H),1.21(s,6H),1.16(s,6H).EIMS m/z 402.2([M+H] + ).
EXAMPLE 8 preparation of Compound I
50g of Compound II was dissolved in 500mL of tetrahydrofuran at 35℃and 56g of DIAD (1.5 eq) and 6g D-proline catalyst were added in this order, the reaction solution was stirred for 12 hours, the insoluble matter was filtered, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (89 g, yield 88%, ee value 98.3%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 7.
EXAMPLE 9 preparation of Compound I
350g of Compound II are dissolved in 2.5L of acetonitrile at 40℃and 287g of DIAD (1.1 eq) and 114g of quinine catalyst are added in sequence, the reaction solution is stirred for 12h, the insoluble matter is filtered off, the filtrate is dried by spinning, and then recrystallized with ethyl acetate-petroleum ether, thus obtaining pure Compound I (651 g, yield 92%, ee value 99%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 7.
EXAMPLE 10 preparation of Compound I
900g of Compound II was dissolved in 3L of 1, 2-dichloroethane at 0℃and 671g of DIAD (1.0 eq) and 293g of quinine catalyst were added in this order, the reaction solution was stirred for 12h, the insoluble matter was filtered off, the filtrate was dried by spinning, and then recrystallized from ethyl acetate-petroleum ether to give pure Compound I (1583 g, yield 87%, ee value 99%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 7.
EXAMPLE 11 preparation of Compound IV
3kg of compound I is dissolved in 15L of triethylene glycol at 25 ℃, 1.6L of hydrazine hydrate (4 eq) is added, the mixture is heated to 120 ℃ for refluxing for 1 hour, the temperature is reduced to 25 ℃, 0.15kg of potassium hydroxide is added, the mixture is heated to 190 ℃ for distillation for 2 hours, the mixture is cooled to 80 ℃, 50L of water is added, white solid is separated out, the mixture is filtered, a filter cake is washed with water, and then acetone-toluene is used for recrystallization, thus obtaining pure compound IV (1.6 kg, yield 90% and ee value 99.4%).
1 H-NMR(300MHz,DMSO-d6):δ4.16(s,1H),3.60(m,2H),3.48(m,2H),3.36(s,2H),2.86(m,1H),1.88(m,1H),1.60(m,3H),1.40(s,9H).EIMS m/z 216.1([M+H] + ).
EXAMPLE 12 preparation of Compound IV
900g of compound I is dissolved in 5L of triethylene glycol at 25 ℃, 720mL of hydrazine hydrate (6 eq) is added, the mixture is heated to 130 ℃ for refluxing for 1 hour, the temperature is reduced to 25 ℃, 0.15kg of potassium hydroxide is added, the mixture is heated to 170 ℃ for distillation for 2 hours, the mixture is cooled to 80 ℃, 15L of water is added, white solid is separated out, the mixture is filtered, a filter cake is washed with water, and then acetone-toluene is used for recrystallization, thus obtaining pure compound IV (477 g, yield 92%, ee value 99.7%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 11.
EXAMPLE 13 preparation of Compound IV
500g of compound I is dissolved in 3L of triethylene glycol at 25 ℃, 200mL of hydrazine hydrate (3 eq) is added, the mixture is heated to 140 ℃ and refluxed for 1 hour, the temperature is reduced to 25 ℃, 0.15kg of sodium hydroxide is added, the mixture is heated to 150 ℃ and distilled for 2 hours, the mixture is cooled to 80 ℃, 10L of water is added, white solid is separated out, the mixture is filtered, a filter cake is washed with water, and then acetone-toluene is used for recrystallization, thus obtaining pure compound IV (274 g, yield 95%, ee value 99.8%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 11.
EXAMPLE 14 preparation of Compound IV
600g of compound I is dissolved in 3.6L of diethylene glycol at 25 ℃, 240mL of hydrazine hydrate (3 eq) is added, the mixture is heated to 150 ℃ for reflux for 1 hour, the temperature is reduced to 25 ℃, 0.15kg of sodium hydroxide is added, the mixture is heated to 160 ℃ for distillation for 2 hours, the mixture is cooled to 80 ℃, 12L of water is added, white solid is separated out, filtration and filter cake water washing are carried out, and then acetone-toluene recrystallization is carried out, thus obtaining pure compound IV (332 g, yield 96%, ee value 99.6%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 11.
EXAMPLE 15 preparation of Compound IV
800g of compound I is dissolved in 4L of methanol at 25 ℃, 1200g of p-toluenesulfonyl hydrazide (3 eq) is added, the mixture is heated to reflux for 2 hours, the temperature is reduced to 25 ℃, 326g of sodium borohydride is slowly added, the mixture is heated to reflux for 2 hours, the mixture is cooled to 25 ℃, 16L of water is added, white solid is separated out, the mixture is filtered, a filter cake is washed with water, and then acetone-toluene is used for recrystallization, thus obtaining pure compound IV (438 g, yield 95%, ee value 99.2%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 11.
EXAMPLE 16 preparation of Compound IV
At 25 ℃, 1200g of compound I is dissolved in 6L of methanol, 2400g of p-toluenesulfonyl hydrazine (3 eq) is added, the mixture is heated to reflux for 2 hours, the temperature is reduced to 25 ℃, 549g of sodium cyanoborohydride is slowly added, the mixture is heated to reflux for 3 hours, the mixture is cooled to 25 ℃, 24L of water is added, white solid is separated out, the mixture is filtered, the filter cake is washed with water, and then acetone-toluene is used for recrystallization, thus obtaining pure compound iv (332 g, yield 96%, ee value 99.0%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 11.
EXAMPLE 17 preparation of Compound IV
300g of compound I is dissolved in 1.5L of methanol at 25 ℃, 321g of p-toluenesulfonyl hydrazine (3 eq) is added, the mixture is heated to reflux for 2 hours, the temperature is reduced to 25 ℃, 137g of sodium cyanoborohydride is slowly added, the mixture is heated to reflux for 4 hours, the mixture is cooled to 25 ℃, 24L of water is added, white solid is separated out, the mixture is filtered, a filter cake is washed with water, and then acetone-toluene is used for recrystallization, thus obtaining pure compound IV (168 g, yield is 97%, ee value is 98.5%). Nuclear magnetic resonance and mass spectrometry data were consistent with example 11.
The hydrazine compound can also be tert-butyl carbazate.
The above examples are only illustrative of the invention and are not intended to limit the invention to the particular embodiments thereof. Modifications and improvements in various other forms will occur to those skilled in the art upon the foregoing description. Obvious modifications or improvements are thus extended within the scope of the invention, which is defined in the appended claims.

Claims (8)

1. The preparation method of the chiral hydrazinopiperidine derivative compound IV comprises the following steps:
the preparation process comprises the following steps:
step a: reacting the compound II with azodicarbonate in the presence of an organic solvent and a chiral small organic molecule catalyst to obtain a compound I;
step b: reacting the compound I with a hydrazine compound in an organic solvent and alkali to obtain a chiral hydrazinopiperidine derivative IV;
wherein R is 1 Is ethyl or isopropyl;
the chiral small organic molecule catalyst is selected from quinine, cinchonidine, D-proline or diphenyl prolinol trimethyl silyl ether;
the base is independently selected from potassium hydroxide, sodium borohydride, or sodium cyanoborohydride;
the hydrazine compound is independently selected from hydrazine hydrate, p-toluenesulfonyl hydrazine or tert-butyl hydrazinoformate.
2. The process for preparing chiral hydrazinopiperidine derivative compound iv according to claim 1: the organic solvent in step a is selected from tetrahydrofuran, ethyl acetate, dichloromethane, 1, 2-dichloroethane or acetonitrile.
3. The process for preparing chiral hydrazinopiperidine derivative compound iv according to claim 1: the molar ratio of the compound II to the azodicarbonate in the step a is 1:0.9-2.0.
4. The process for preparing chiral hydrazinopiperidine derivative compound iv according to claim 1: in step b, the organic solvent is independently selected from tetrahydrofuran, diglycolide, triglycolide, methanol, ethanol or acetonitrile.
5. The process for preparing chiral hydrazinopiperidine derivative compound iv according to claim 1: in the step b, the molar ratio of the alkali to the compound I is 1-4.0:1; the molar ratio of the hydrazine compound to the compound I is 1-8.0:1.
6. Compound i:
wherein R is 1 Is ethyl or isopropyl.
7. The preparation method of the compound I comprises the following steps:
reacting the compound II with azodicarbonate under the conditions of an organic solvent and a chiral small organic molecule catalyst to obtain a compound I; wherein R is 1 Is ethyl or isopropyl;
the chiral small organic molecule catalyst is selected from quinine, cinchonidine, D-proline or diphenyl prolinol trimethyl silyl ether.
8. The preparation method of the compound IV comprises the following steps:
reacting the compound I with a hydrazine compound in an organic solvent and alkali to obtain a chiral hydrazinopiperidine derivative IV; wherein R is 1 Is ethyl or isopropyl;
the base is independently selected from potassium hydroxide, sodium borohydride, or sodium cyanoborohydride;
the hydrazine compound is independently selected from hydrazine hydrate, p-toluenesulfonyl hydrazine or tert-butyl hydrazinoformate.
CN202210069453.4A 2021-02-05 2022-01-21 Process for preparing chiral hydrazinopiperidine derivatives Active CN114853662B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2021101602747 2021-02-05
CN202110160274 2021-02-05

Publications (2)

Publication Number Publication Date
CN114853662A CN114853662A (en) 2022-08-05
CN114853662B true CN114853662B (en) 2024-01-12

Family

ID=82627391

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210069453.4A Active CN114853662B (en) 2021-02-05 2022-01-21 Process for preparing chiral hydrazinopiperidine derivatives

Country Status (1)

Country Link
CN (1) CN114853662B (en)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008036308A2 (en) * 2006-09-18 2008-03-27 Signal Pharmaceuticals, Llc Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
CN103664742A (en) * 2012-09-12 2014-03-26 上海药明康德新药开发有限公司 Preparation method of trans-N-Boc-3-amino-4-hydroxypiperidine
CN103664743A (en) * 2012-09-12 2014-03-26 上海药明康德新药开发有限公司 Preparation method of (3S, 4R)-3-amido-4-methyl piperidine-1-tertiary butyl carboxylate
CN107108640A (en) * 2015-01-14 2017-08-29 药品循环有限责任公司 The synthesis of bruton's tyrosine kinase inhibitor
CN107383017A (en) * 2017-07-20 2017-11-24 河南师范大学 Buddhist nun's high efficiency preparation method is replaced according to Shandong
CN107385966A (en) * 2017-07-20 2017-11-24 毛龙飞 A kind of leather-like dyeing assistant of novel organosilicon and preparation method thereof
CN109180683A (en) * 2018-09-07 2019-01-11 南通雅本化学有限公司 A kind of preparation method for replacing Buddhist nun according to Shandong

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008036308A2 (en) * 2006-09-18 2008-03-27 Signal Pharmaceuticals, Llc Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
CN103664742A (en) * 2012-09-12 2014-03-26 上海药明康德新药开发有限公司 Preparation method of trans-N-Boc-3-amino-4-hydroxypiperidine
CN103664743A (en) * 2012-09-12 2014-03-26 上海药明康德新药开发有限公司 Preparation method of (3S, 4R)-3-amido-4-methyl piperidine-1-tertiary butyl carboxylate
CN107108640A (en) * 2015-01-14 2017-08-29 药品循环有限责任公司 The synthesis of bruton's tyrosine kinase inhibitor
CN107383017A (en) * 2017-07-20 2017-11-24 河南师范大学 Buddhist nun's high efficiency preparation method is replaced according to Shandong
CN107385966A (en) * 2017-07-20 2017-11-24 毛龙飞 A kind of leather-like dyeing assistant of novel organosilicon and preparation method thereof
CN109180683A (en) * 2018-09-07 2019-01-11 南通雅本化学有限公司 A kind of preparation method for replacing Buddhist nun according to Shandong

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Detlef Kampmann，等.A Large-Scale Low-Cost Access to the Lithium 2,2,6,6-Tetramethylpiperidide Precursor .《SYNTHESIS》.2004,(第6期),1028-1029. *
Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with In Vivo Antitumor Activity;Paul R. Leger，等;《Journal of Medicinal Chemistry》;第63卷;5398−5420 *

Also Published As

Publication number Publication date
CN114853662A (en) 2022-08-05

Similar Documents

Publication Publication Date Title
JP2014501719A (en) Chiral spiro-pyridylamidophosphine ligand compound, synthesis method thereof and use thereof
CN113999142B (en) Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine
CN102952088B (en) Preparation method of dexrazoxane
US9771317B2 (en) Process for preparing lacosamide and related compounds
CN113636950B (en) Preparation method of chiral 4-aryl-beta-amino acid derivative
CN109535120B (en) Preparation method of 7-substituted-3, 4,4, 7-tetrahydrocyclobutane coumarin-5-ketone
CN114853662B (en) Process for preparing chiral hydrazinopiperidine derivatives
CN110981779B (en) Synthesis method of R-2- (2, 5-difluorophenyl) pyrrolidine
CN112939849B (en) (S, S) -2, 8-diazabicyclo [4.3.0] nonane intermediate and preparation method and application thereof
CN113979982A (en) Preparation method and application of chiral dihydrochromone-2-carboxylic acid compound and derivative thereof
CN107827916B (en) Synthesis method of (R) - (1-amino-3-methyl) butyl-1-pinanediol borate
US8710239B2 (en) Process for preparing synthetic intermediates of peripherally-selective inhibitors of dopamine-β-hydroxylase involving catalytic asymmetric hydrogenation
CN107325049B (en) Preparation method of neratinib intermediate
CN111217847A (en) Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction
CN114805172B (en) Method for synthesizing asymmetric heterocyclic diaryl methane compound
CN115304557B (en) Enamine derivative and preparation method thereof
CN109721630A (en) A kind of synthetic method of Ugi ' s amine and its derivative
CN115819208B (en) Synthesis method of 2-aryl-3, 4-dihydro-1 (2H) -naphthalenone compound
CN110835319B (en) Synthesis method of benazepril intermediate and benazepril hydrochloride
CN112552200B (en) Preparation method of optical pure 4- (1-amino) ethyl benzoate and salt thereof
CN113912544B (en) Preparation method of 5-bromo-1-methylindazole
CN111138333B (en) Preparation method of (R) -2- (2, 5-difluorophenyl) -pyrrolidine
CN109776400B (en) Preparation method of (R) -phenyl (pyridine-2-yl) methanol derivative
KR20100054627A (en) Binaphthol aldehyde derivatives and method for preparing the same
JPH11255759A (en) Production of optically active beta-lactone

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant