Lithium Hydroxide → 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-carboxylic acid

HRID 1508599노트

반응식

HRID 1508599 반응식
[F:1][C:2]([F:52])([F:51])[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:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([O:42]C)=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([N:45]4[CH:49]=[CH:48][CH:47]=[N:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Li+]>C(O)(C(F)(F)F)=O>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([OH:42])=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([N:45]4[CH:49]=[CH:48][CH:47]=[N:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:4]=[C:3]([C:2]([F:1])([F:52])[F:51])[CH:8]=1

참가 물질

4

반응물 2

HCID 3939Lithium HydroxideHCID 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-carboxylate

생성물 1

HCID 569715943'-[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-carboxylic acid수율 82.5%

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

반응 조건

온도
40 °C

실험 절차

To 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) in dioxanes (2 mL) was added lithium hydroxide (0.5 M, 1.0 mL, 0.505 mmol). The system was heated to 40° C. and was stirred for 1.5 hrs. The reaction was cooled to room temperature and TFA (100 μL) was added to the reaction before volatiles were removed. The crude material was purified by reverse phase HPLC to yield 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-carboxylic acid (86.1 mg, 0.104 mmol). LCMS calc.=711.2. found=711.2. 1H NMR (CD3OD, 500 MHz) δ 8.62 (s, 1H), 7.88 (m, 8H), 7.34 (m, 4H), 6.56 (s, 1H), 5.81 (m, 1H), 4.84 (m, 1H), 4.24 (m, 2H), 3.90 (br s, 3H), 3.36 (br s, 3H), 0.67 (d, J=33.5 Hz, 3H). RTA=14.8 nM

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. customwere removed
  3. customThe crude material was purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-5fe0103790ba4e688315767a497060ab
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221834B2

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