Water → 3-[(9-Fluoro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 548705노트

반응식

HRID 548705 반응식
CC([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]([CH3:21])[C:10](=[O:20])[C:11]1[CH:16]=[CH:15][C:14](F)=[C:13]([F:18])[C:12]=1F)(C)C.[OH:24][C:25]1[CH:26]=[C:27]([CH:37]=[C:38]([O:40][C@@H:41]([CH3:45])[CH2:42][O:43][CH3:44])[CH:39]=1)[C:28]([NH:30][C:31]1[CH:35]=[CH:34][N:33]([CH3:36])[N:32]=1)=[O:29].C(=O)([O-])[O-].[K+].[K+].O>CC(N(C)C)=O>[F:18][C:13]1[C:12]2[O:6][CH2:7][CH2:8][N:9]([CH3:21])[C:10](=[O:20])[C:11]=2[CH:16]=[CH:15][C:14]=1[O:24][C:25]1[CH:26]=[C:27]([CH:37]=[C:38]([O:40][C@@H:41]([CH3:45])[CH2:42][O:43][CH3:44])[CH:39]=1)[C:28]([NH:30][C:31]1[CH:35]=[CH:34][N:33]([CH3:36])[N:32]=1)=[O:29]

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57663171N-(2-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,3,4-trifluoro-N-methylbenzamideHCID 591271783-hydroxy-5-{[(2S)-1-methoxypropan-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

생성물 1

HCID 159495893-[(9-Fluoro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide수율 75.1%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
140 °C

실험 절차

A suspension of N-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,3,4-trifluoro-N-methylbenzamide (300 mg, 0.86 mmol), 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (278 mg, 0.91 mmol) and potassium carbonate (237 mg, 1.73 mmol) in DMA (20 mL) was heated to 140° C. for 1 hour. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine (50 mL) and dried (MgSO4), filtered and evaporated to give an orange oil. This was purified via column chromatography on silica, eluting with 50-100% ethyl acetate in isohexane, to give the desired product as a colourless oil (322 mg). 1H NMR δ (CDCl3): 1.25 (d, 3H), 2.77 (s, 3H), 3.33 (s, 3H), 3.44 (dd, 1H), 3.50 (dd, 1H), 3.71 (s, 3H), 3.74 (t, 2H), 4.25 (t, 2H), 4.49-4.56 (m, 1H), 6.71 (d, 1H), 6.73 (t, 1H), 6.75 (dd, 1H), 7.04 (t, 1H), 7.20-7.20 (m, 1H), 7.22 (d, 1H), 7.47 (dd, 1H), 8.68 (s, 1H); m/z 499 (M+H)+

후처리

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. washThe combined organic phases were washed with brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give an orange oil
  7. customThis was purified via column chromatography on silica
  8. washeluting with 50-100% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-a2e28474dd8245f08b91bd557c433a84
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943607B2

반응 노트

불러오는 중…