HCID 12504008, 화합물 → 1-((3R,4R)-3-(4-chloro-6-methylpyridin-2-ylamino)-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

HRID 1666612노트

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HRID 1666612 반응식
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH3:9])[N+:3]=1[O-].[NH2:11][C@H:12]1[C@H:16]([OH:17])[CH2:15][N:14]([C:18](=[O:31])[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=2)[CH2:13]1>C(O)CCC>[Cl:8][C:6]1[CH:5]=[C:4]([CH3:9])[N:3]=[C:2]([NH:11][C@H:12]2[C@H:16]([OH:17])[CH2:15][N:14]([C:18](=[O:31])[CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][C:27]([F:28])([F:29])[F:30])=[CH:24][CH:25]=3)[CH2:13]2)[CH:7]=1

참가 물질

4

반응물 2

HCID 12504008HCID 12504008, 화합물HCID 579701111-((3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

생성물 1

HCID 579701641-((3R,4R)-3-(4-chloro-6-methylpyridin-2-ylamino)-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone수율 15.6%

시약·촉매·용매 1

HCID 2631-Butanol용매

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온도
130 °C

실험 절차

A mixture of 2,4-dichloro-6-methylpyridine 1-oxide (200 mg), 1-((3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (340 mg), and n-butanol (0.6 mL) was stirred at 130° C. for 10 h. The reaction mixture was concentrated under reduced pressure, the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate−ethyl acetate/methanol=20:1), and then the resulting solids were washed with hexane and diethyl ether to obtain 1-((3R,4R)-3-(4-chloro-6-methylpyridin-2-ylamino)-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (75 mg). (2) A mixture of 1-((3R,4R)-3-(4-chloro-6-methylpyridin-2-ylamino)-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (68 mg), morpholine (0.02 mL), sodium t-butoxide (42 mg), Pd(OAc)2 (1 mg), 2-(di-t-butylphosphino)biphenyl (3 mg), and toluene (1 mL) was heated at 100° C. for 10 h. The mixture was cooled to room temperature, then the reaction mixture was diluted with chloroform, insoluble matters were removed by Celite filtration, and then the filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (NH silica gel, ethyl acetate, and silica gel, hexane/acetone=1:1) to obtain the title compound (8 mg).

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate−ethyl acetate/methanol=20:1)
  3. washthe resulting solids were washed with hexane and diethyl ether

출처 및 근거

ORD 기록
ord-7e560da297d447df9e603b55b32b3df0
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044068B2

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