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

HRID 1666612ノート

反応式

HRID 1666612 の反応式
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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 2631-Butanol溶媒

反応条件

温度
130 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7e560da297d447df9e603b55b32b3df0
出典データセット
uspto-grants-2011_10
特許番号
US08044068B2

反応ノート

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