Cesium carbonate → 3-[(2,3-Dimethyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide

HRID 548764노트

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HRID 548764 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[S:18][N:17]=[C:16]([CH3:19])[N:15]=1)=[O:12].F[C:29]1[CH:41]=[CH:40][C:32]2[C:33](=[O:39])[N:34]([CH3:38])[CH2:35][CH2:36][O:37][C:31]=2[CH:30]=1>CC(N(C)C)=O>[CH3:35][CH:36]1[N:34]([CH3:38])[C:33](=[O:39])[C:32]2[CH:40]=[CH:41][C:29]([O:7][C:8]3[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=3)[C:11]([NH:13][C:14]3[S:18][N:17]=[C:16]([CH3:19])[N:15]=3)=[O:12])=[CH:30][C:31]=2[O:37]1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 576631608-fluoro-4-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-oneHCID 591271603-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide

생성물 1

HCID 159500393-[(2,3-Dimethyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide수율 64.4%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
160 °C

실험 절차

Cesium carbonate (489 mg, 1.5 mmol) was added to a solution of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide (155 mg, 0.5 mmol) and 8-fluoro-4-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (117 mg, 0.6 mmol) in DMA (5 mL) and the stirred mixture heated at 160° C. in a microwave reactor for 8 hours. The mixture was cooled to RT and pressure, the DMA removed in vacuo, and the residue partitioned between water (25 mL) and ethyl acetate (30 mL). The mixture was adjusted to pH 2, the organic layer washed with brine, dried (MgSO4) and evaporated in vacuo to a residue which was chromatographed on silica, eluting with ethyl acetate, to give desired compound (156 mg). 1H NMR δ (CDCl3): 1.3 (d, 3H), 1.5 (d, 2H), 2.4 (s, 3H), 3.0 (s, 3H), 3.7 (d, 2H), 4.5 (m, 1H), 5.35 (q, 1H), 6.4 (s, 1H), 6.6 (d, 1H), 6.75 (s, 1H), 7.15 (s, 1H), 7.2 (s, 1H), 7.8 (d, 1H); m/z 485 (M+H)+

후처리

  1. temperatureThe mixture was cooled to RT
  2. custompressure, the DMA removed in vacuo
  3. customthe residue partitioned between water (25 mL) and ethyl acetate (30 mL)
  4. washthe organic layer washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo to a residue which
  7. customwas chromatographed on silica
  8. washeluting with ethyl acetate

출처 및 근거

ORD 기록
ord-3d9f88d39d584b38b3dd0aa33e49d68b
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943607B2

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