Diisopropylethylamine → HCID 86693892、化合物

HRID 404841ノート

反応式

HRID 404841 の反応式
[CH2:1]([C:8]1[S:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[C@H:21]([NH:26][CH2:27][C@H:28]1[C@@H:32]([F:33])[CH2:31][N:30]([C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH2:29]1)[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:53]([O:56][C@@H:57]([CH3:61])[C:58](Cl)=[O:59])(=[O:55])[CH3:54]>ClCCl>[C:53]([O:56][C@@H:57]([CH3:61])[C:58]([N:26]([CH2:27][C@H:28]1[C@@H:32]([F:33])[CH2:31][N:30]([C:34]([O:36][CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)=[O:35])[CH2:29]1)[C@@H:21]([C:9]1[N:10]=[C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])[S:12][C:8]=1[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:22]([CH3:25])([CH3:24])[CH3:23])=[O:59])(=[O:55])[CH3:54]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 86693891(3R,4R)-benzyl 3-(((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate

生成物 1

HCID 86693892HCID 86693892、化合物収率 75%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

to a solution of (3R,4R)-benzyl 3-(((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate (130 mg, 0.214 mmol) in dichloromethane (2.1 mL, 0.1 M solution) at room temperature was added N,N-diisopropylethylamine (112 μL, 0.64 mmol). (S)-1-Chloro-1-oxopropan-2-yl acetate (54.2 μL, 0.428 mmol) was then added dropwise over 2 min. The resulting solution was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and filtered. After the volatile organic materials were removed in vacuo, the crude product was purified on flash column chromatography to yield (3R,4R)-benzyl 3-(((S)-2-acetoxy-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate (115 mg, 75%). NMR (CDCl3, 400 MHz): δ 7.85 (1H, m), 7.37-7.24 (7H, m), 7.21 (1H, m), 7.09 (2H, m), 7.05 (1H, m), 6.96 (1H, m), 6.1 (1H, m), 5.4 (2H, m), 5.28 (1H, m), 4.82 (2H, m), 4.19-3.97 (3H, m), 3.70-3.49 (2H, m), 3.13 (1H, m), 2.76 (1H, m), 2.52 (1H, m), 2.18 (3H, s), 1.61 (3H, m), 0.99 (9H, s). LC/MS (uplc): MH+ 722.3, 1.40 min.

後処理

  1. customThe reaction mixture was quenched with saturated NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customAfter the volatile organic materials were removed in vacuo
  7. customthe crude product was purified on flash column chromatography

出典と根拠

ORDレコード
ord-1c88fa39a38243f5806b3544b3e99e6f
出典データセット
uspto-grants-2014_06
特許番号
US08748626B2

反応ノート

読み込み中…