Water → 2-Propen-1-yl {3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}carbamate

HRID 239268노트

반응식

HRID 239268 반응식
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([F:24])=[C:13]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[O:33]1[CH2:38][CH2:37][CH:36]([C:39](=[S:41])[NH2:40])[CH2:35][CH2:34]1.O>CC(N(C)C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:41][C:39]([CH:36]3[CH2:37][CH2:38][O:33][CH2:34][CH2:35]3)=[N:40][C:9]=2[C:11]2[C:12]([F:24])=[C:13]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 67184N-bromobutanimideHCID 13197204Oxane-4-carbothioamideHCID 579899922-Propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate

생성물 1

HCID 579899832-Propen-1-yl {3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}carbamate수율 35%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

To a solution of 2-propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate (85 g, 243 mmol) in DMA (700 mL), NBS (43.2 g, 243 mmol) was added at 0° C. The reaction mixture was stirred at rt for 1 h. Then tetrahydro-2H-pyran-4-carbothioamide (42.3 g, 291.6 mmol) was added at rt. The mixture was stirred at 60° C. for 1.5 h. The mixture was poured into water and extracted with EtOAc (400 mL×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. (40 g, 35% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.48-9.54 (br, 1H), 8.58 (d, J=5.3 Hz, 1H), 7.76-7.83 (m, 1H), 7.23-7.32 (m, 2H), 7.02 (d, J=5.3 Hz, 1H), 5.87-5.98 (m, 1H), 5.27-5.36 (m, 1H), 5.16-5.21 (m, 1H), 4.54-4.60 (m, 2H), 3.87-3.94 (m, 2H), 3.41-3.50 (m, 2H), 3.27-3.37 (m, 1H), 1.97-2.04 (m, 2H), 1.69-1.82 (m, 2H).

후처리

  1. stirringThe mixture was stirred at 60° C. for 1.5 h
  2. extractionextracted with EtOAc (400 mL×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)

출처 및 근거

ORD 기록
ord-42c4eaa5d615472b93013656b07968f3
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642759B2

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