Potassium Carbonate → methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

HRID 1508598노트

반응식

HRID 1508598 반응식
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25](Br)=[CH:24][CH:23]=[C:22]([N:27]4[CH:31]=[CH:30][CH:29]=[N:28]4)[N:21]=3)[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:35][O:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[CH:48]=[CH:47][C:46]([C:49]([O:51][CH3:52])=[O:50])=[CH:45][C:44]=2[CH3:53])=[CH:39][C:38]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:38]4[CH:39]=[C:40]([C:43]5[CH:48]=[CH:47][C:46]([C:49]([O:51][CH3:52])=[O:50])=[CH:45][C:44]=5[CH3:53])[CH:41]=[CH:42][C:37]=4[O:36][CH3:35])=[CH:24][CH:23]=[C:22]([N:27]4[CH:31]=[CH:30][CH:29]=[N:28]4)[N:21]=3)[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 57692976HCID 57692976, 화합물HCID 86704645(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(1H-pyrazol-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

생성물 1

HCID 86704646methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate수율 69.2%

시약·촉매·용매 2

HCID 178454861HCID 178454861, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

To (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(1H-pyrazol-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (100 mg, 0.182 mmol) in THF (0.91 mL) was added methyl 4′-methoxy-2-methyl-3′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate (84 mg, 0.218 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (17.8 mg, 0.027 mmol), and potassium carbonate (2 M in water, 0.273 mL, 0.546 mmol). The system was flushed with nitrogen, capped, and stirred at room temperature overnight. The reaction was diluted with ethyl acetate and the organic was washed with water (2×), brine, dried (Na2SO4), filtered, and concentrated. The crude material was purified by column chromatography to yield methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (91.4 mg, 0.126 mmol). LCMS calc.=725.2. found=725.3.

후처리

  1. customThe system was flushed with nitrogen
  2. customcapped
  3. additionThe reaction was diluted with ethyl acetate
  4. washthe organic was washed with water (2×), brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by column chromatography

출처 및 근거

ORD 기록
ord-fafad854e4374ac6b78feadbe9e5c278
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221834B2

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