Triethylamine → 3-[(3,5-Difluorophenyl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20508노트

반응식

HRID 20508 반응식
[Si]([O:8][CH2:9][C@H:10]([CH3:28])[O:11][C:12]1[CH:13]=[C:14]([CH:24]=[C:25]([OH:27])[CH:26]=1)[C:15]([NH:17][C:18]1[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=1)=[O:16])(C(C)(C)C)(C)C.[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[C:34]([F:36])[CH:35]=1.C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:29][C:30]1[CH:31]=[C:32]([O:27][C:25]2[CH:24]=[C:14]([CH:13]=[C:12]([O:11][C@@H:10]([CH3:28])[CH2:9][OH:8])[CH:26]=2)[C:15]([NH:17][C:18]2[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=2)=[O:16])[CH:33]=[C:34]([F:36])[CH:35]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 536296323-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

생성물 1

HCID 116757593-[(3,5-Difluorophenyl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide수율 22.3%

시약·촉매·용매 2

HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매

실험 절차

A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (202 mg, 0.5 mmol), 3,5-difluorophenylboronic acid (156 mg, 1.0 mmol), copper (II) acetate (182 mg, 1.0 mmol), triethylamine (252 mg, 2.5 mmol) and freshly activated 4 Å molecular sieves (1.5 g) in DCM (10 mL) was stirred at ambient temperature and under ambient atmosphere for 64 hours. The reaction mixture was filtered, washed with DCM (2×10 mL), evaporated in vacuo and the residual oil partitioned between ethyl acetate (25 mL) and 1M hydrochloric acid (10 mL). The ethyl acetate layer was separated, washed sequentially with aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), and evaporated to a residue which was chromatographed by preparative HPLC on C18 reversed phase using 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA) as eluant to give the title compound (45 mg).

후처리

  1. filtrationThe reaction mixture was filtered
  2. washwashed with DCM (2×10 mL)
  3. customevaporated in vacuo
  4. customthe residual oil partitioned between ethyl acetate (25 mL) and 1M hydrochloric acid (10 mL)
  5. customThe ethyl acetate layer was separated
  6. washwashed sequentially with aqueous sodium hydrogen carbonate solution and brine
  7. dry with materialdried (MgSO4)
  8. customevaporated to a residue which
  9. customwas chromatographed by preparative HPLC on C18 reversed phase

출처 및 근거

ORD 기록
ord-92dde1c0049c4877a8fae7acf59b2742
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745475B2

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