Dimethylamine → rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid {1-[2-((R)-3-dimethylamino-2-hydroxy-propoxy)-2-methyl-propyl]-1H-pyrazol-3-yl)-amide

HRID 1807107ノート

反応式

HRID 1807107 の反応式
[CH3:1][C:2]([O:41][CH2:42][C@H:43]1[CH2:45][O:44]1)([CH3:40])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:13]2)=[O:11])=[N:5]1.[CH3:46][NH:47][CH3:48]>C(O)(C)C>[CH3:46][N:47]([CH3:48])[CH2:45][C@@H:43]([OH:44])[CH2:42][O:41][C:2]([CH3:1])([CH3:40])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:37])([CH3:39])[CH3:38])[NH:13]2)=[O:11])=[N:5]1

参加物

4

反応物 2

HCID 674DimethylamineHCID 86640459HCID 86640459、化合物

生成物 1

HCID 86640468rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid {1-[2-((R)-3-dimethylamino-2-hydroxy-propoxy)-2-methyl-propyl]-1H-pyrazol-3-yl)-amide収率 20.1%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

A mixture of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethylpropyl)-pyrrolidine-2-carboxylic acid {1-[2-methyl-2-((R)-1-oxiranylmethoxy)-propyl]-1H-pyrazol-3-yl}-amide (0.69 g, 1.04 mmol), isopropyl alcohol (2 mL), and dimethylamine (1.04 mL, 2.08 mmol, 2 M in THF) was microwaved at 130° C. for 15 min. The mixture was extracted with dichloromethane and water. The organic layer was separated and the solvent evaporated under reduced pressure. The resulting oil was purified by column chromatography (50% ethyl acetate/heptane) to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid {1-[2-((R)-3-dimethylamino-2-hydroxy-propoxy)-2-methyl-propyl]-1H-pyrazol-3-yl)-amide (147.2 mg, 20.05%) as a white powder. HRMS (ES+) m/z Calcd for C35H44Cl2F2N6O3S+H [(M+H)+]: 705.2893. found: 705.2893.

後処理

  1. customwas microwaved at 130° C. for 15 min
  2. extractionThe mixture was extracted with dichloromethane and water
  3. customThe organic layer was separated
  4. customthe solvent evaporated under reduced pressure
  5. customThe resulting oil was purified by column chromatography (50% ethyl acetate/heptane)

出典と根拠

ORDレコード
ord-b510e6521e954c04beb4d3a41b399044
出典データセット
uspto-grants-2013_01
特許番号
US08354444B2

反応ノート

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