N-bromobutanimide → 2-Propen-1-yl {5-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}carbamate

HRID 239279ノート

反応式

HRID 239279 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[CH:13][C:14]([F:24])=[C:15]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[CH3:33][C:34]([CH3:39])([CH3:38])[C:35](=[S:37])[NH2:36]>O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:37][C:35]([C:34]([CH3:39])([CH3:38])[CH3:33])=[N:36][C:9]=2[C:11]2[CH:12]=[CH:13][C:14]([F:24])=[C:15]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:16]=2)[CH:5]=[CH:4][N:3]=1

参加物

5

反応物 3

HCID 67184N-bromobutanimideHCID 30311302,2-DimethylpropanethioamideHCID 579897362-Propen-1-yl {5-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate

生成物 1

HCID 579900012-Propen-1-yl {5-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}carbamate収率 80.5%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

To a solution of 2-propen-1-yl {5-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate (35 g, 100.3 mmol in DMA, 500 mL), NBS (17.8 g, 100.3 mmol) was added. The reaction mixture was stirred at rt for 1 h. Then 2,2-dimethylpropanethioamide (13 g, 111 mmol) was added at 0° C. The mixture was stirred at 80° C. for 2 h. The mixture was poured into water and extracted with EtOAc (1 L×3). The combined organic layers were washed with water and brine successively, dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel (DCM:petroleum ether 2:1) to afford the title compound (36 g, 80.5% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.24-8.31 (m, 2H), 7.09-7.18 (m, 2H), 7.01 (d, J=5.5 Hz, 1H), 6.92-6.98 (br, 1H), 5.87-5.97 (m, 1H), 5.31-5.37 (m, 1H), 5.24-5.28 (m, 1H), 4.61-4.65 (m, 2H), 1.46 (s, 9H).

後処理

  1. stirringThe mixture was stirred at 80° C. for 2 h
  2. extractionextracted with EtOAc (1 L×3)
  3. washThe combined organic layers were washed with water and brine successively
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product, which
  8. customwas purified by column chromatography on silica gel (DCM:petroleum ether 2:1)

出典と根拠

ORDレコード
ord-c0dae52e2c8c4ecb8978b83cb4ab2846
出典データセット
uspto-grants-2014_02
特許番号
US08642759B2

反応ノート

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