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

HRID 20508Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 20508
[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

Komponenten

6

Edukt 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

Produkt 1

HCID 116757593-[(3,5-Difluorophenyl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamideAusbeute 22,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8895Cupric acetateKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-92dde1c0049c4877a8fae7acf59b2742
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745475B2

Notizen zur Reaktion

Wird geladen…