Water → 3-[(8-chloro-2,3-dimethyl-4-oxo-3,4-dihydro-2h-1,3-benzoxazin-7-yl)oxy]-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-n-(1-methyl-1h-pyrazol-3-yl)benzamide

HRID 548696노트

반응식

HRID 548696 반응식
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@H:18]([CH2:21][OH:22])[CH2:19][CH3:20])[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].[Si](O[CH2:31][CH2:32][N:33]([CH3:45])[C:34](=[O:44])[C:35]1[CH:40]=[CH:39][C:38](F)=[C:37]([Cl:42])[C:36]=1F)(C(C)(C)C)(C)C.C(=O)([O-])[O-:47].[K+].[K+].O>CC(N(C)C)=O>[Cl:42][C:37]1[C:36]2[O:47][CH:32]([CH3:31])[N:33]([CH3:45])[C:34](=[O:44])[C:35]=2[CH:40]=[CH:39][C:38]=1[O:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@H:18]([CH2:21][OH:22])[CH2:19][CH3:20])[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6]

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57663164N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamideHCID 591271493-hydroxy-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

생성물 1

HCID 159494963-[(8-chloro-2,3-dimethyl-4-oxo-3,4-dihydro-2h-1,3-benzoxazin-7-yl)oxy]-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-n-(1-methyl-1h-pyrazol-3-yl)benzamide수율 159.5%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

A solution of 3-hydroxy-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.66 mmol), N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamide (239 mg, 0.66 mmol) and potassium carbonate (181 mg, 1.31 mmol) in DMA (3 mL) was heated in a microwave reactor at 160° C. for 6 hours. Water (20 mL) was added and the reaction mixture extracted with ethyl acetate. The organic layer was washed with brine (20 mL), dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 2% methanol in ethyl acetate, and then chromatographed by preparative HPLC on C18 reversed phase, eluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA), to give the required product (542 mg).

후처리

  1. extractionthe reaction mixture extracted with ethyl acetate
  2. washThe organic layer was washed with brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. customevaporated to a residue which
  5. customwas chromatographed on silica
  6. washeluting with 2% methanol in ethyl acetate
  7. customchromatographed by preparative HPLC on C18 reversed phase
  8. washeluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA)

출처 및 근거

ORD 기록
ord-140cbb0bf8274483a33c587fb88554d2
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943607B2

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