Diisopropylethylamine → HCID 72244027、化合物

HRID 1807222ノート

反応式

HRID 1807222 の反応式
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.[NH2:32][C:33]1[CH:37]=[CH:36][S:35][C:34]=1[C:38](=[O:40])[CH3:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:38]([C:34]1[S:35][CH:36]=[CH:37][C:33]=1[NH:32][C:28]([CH:9]1[CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:31])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10]1)=[O:29])(=[O:40])[CH3:39]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 27352332-Acetyl-3-aminothiopheneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666882513-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

生成物 1

HCID 72244027HCID 72244027、化合物

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

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-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (200 mg, 0.43 mmol), 1-(3-aminothiophen-2-yl)ethanone (140 mg, 0.98 mmol), 2-(7-azabenzotriazol-1-yl)-n,n,n′,n′-tetramethyluronium hexafluorophosphate (HATU, 243.3 mg, 0.64 mmol) and iPr2NEt (0.3 mL, 1.67 mmol) in CH2Cl2 (5 mL) was stirred at rt overnight. The mixture was then diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, dried over Na2SO4 and filtered. The mixture was then concentrated and purified flash column chromatography (1-100% ethyl acetate/heptane) to afford 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 (2-acetyl-thiophen-3-yl)-amide as a off white powder (40 mg, 15.8%). HRMS (ES+) m/z Calcd for C29H27Cl2F2N3O2S+H [(M+H)+]: 590.1242. found: 590.1244.

後処理

  1. washwashed with water, brine
  2. customThe organic phase was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe mixture was then concentrated
  6. custompurified flash column chromatography (1-100% ethyl acetate/heptane)

出典と根拠

ORDレコード
ord-1c0ec83129b543898987277e4c55408d
出典データセット
uspto-grants-2013_01
特許番号
US08354444B2

反応ノート

読み込み中…