Triethylamine → 3-[(2,2-Difluoro-1,3-benzodioxol-5-yl)oxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 548646

반응식

HRID 548646 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([F:42])[O:34][C:33]2[CH:35]=[CH:36][C:37](B(O)O)=[CH:38][C:32]=2[O:31]1.C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:42][C:30]1([F:29])[O:31][C:32]2[CH:38]=[CH:37][C:36]([O:27][C:25]3[CH:24]=[C:14]([CH:13]=[C:12]([O:11][C@@H:10]([CH3:28])[CH2:9][OH:8])[CH:26]=3)[C:15]([NH:17][C:18]3[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=3)=[O:16])=[CH:35][C:33]=2[O:34]1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 17750030(2,2-Difluoro-1,3-dioxaindan-5-yl)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 159491213-[(2,2-Difluoro-1,3-benzodioxol-5-yl)oxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide수율 1.4%

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 (0.20 g, 0.493 mmol), (2,2-difluoro-1,3-benzodioxol-5-yl)boronic acid (303 mg, 1.5 mmol), copper (II) acetate (0.202 g, 1.11 mmol), triethylamine (0.52 mL, 3.71 mmol) and freshly activated 4 Å molecular sieves (1 g) in DCM (40 mL) was stirred at ambient temperature and under ambient atmosphere for 2 days. The reaction mixture was filtered through celite, washed with DCM (2×10 mL), the DCM removed in vacuo. 3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil dissolved in methanol (5 mL) and the mixture stirred at room temperature for 20 minutes. The solution was neutralised with saturated sodium bicarbonate solution, the methanol removed in vacuo and the residual solution partitioned between ethyl acetate (50 mL) and water (10 mL). The ethyl acetate layer was separated, washed with brine, dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with 3% methanol in DCM, to give the desired compound (3.1 mg).

후처리

  1. filtrationThe reaction mixture was filtered through celite
  2. washwashed with DCM (2×10 mL)
  3. customthe DCM removed in vacuo
  4. addition3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil
  5. dissolutiondissolved in methanol (5 mL)
  6. customthe methanol removed in vacuo
  7. customthe residual solution partitioned between ethyl acetate (50 mL) and water (10 mL)
  8. customThe ethyl acetate layer was separated
  9. washwashed with brine
  10. dry with materialdried (MgSO4)
  11. customevaporated to a residue which
  12. customwas chromatographed on silica
  13. washeluting with 3% methanol in DCM

출처 및 근거

ORD 기록
ord-1420a4ccff3d47e4b8ae4fb5a41e43dc
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943607B2

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