Lithium hydroxide, monohydrate → 2-(2-(2-(2-((4-(4-(tert-Butoxycarbonyl)morpholin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

HRID 1473108노트

반응식

HRID 1473108 반응식
C[O:2][C:3](=[O:43])[CH2:4][C:5]1[CH:42]=[CH:41][CH:40]=[CH:39][C:6]=1[CH2:7][CH2:8][C:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][N:12]=[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]3[O:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]3)=[CH:22][CH:21]=2)[N:10]=1.O.[OH-].[Li+]>C1COCC1.O>[C:35]([O:34][C:32]([N:28]1[CH2:29][CH2:30][O:31][CH:26]([C:23]2[CH:24]=[CH:25][C:20]([NH:19][C:11]3[N:10]=[C:9]([CH2:8][CH2:7][C:6]4[CH:39]=[CH:40][CH:41]=[CH:42][C:5]=4[CH2:4][C:3]([OH:43])=[O:2])[C:14]([C:15]([F:16])([F:17])[F:18])=[CH:13][N:12]=3)=[CH:21][CH:22]=2)[CH2:27]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

참가 물질

5

반응물 2

HCID 168937Lithium hydroxide, monohydrateHCID 71229333HCID 71229333, 화합물

생성물 1

HCID 682828512-(2-(2-(2-((4-(4-(tert-Butoxycarbonyl)morpholin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid수율 85%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

tert-Butyl 2-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)morpholine-4-carboxylate (I89) (46 mg, 0.077 mmol) was dissolved in THF (2 mL), and lithium hydroxide hydrate (6.0 mg, 0.15 mmol) in water (0.5 mL) was added. After 18 hours the mixture was concentrated, diluted with water (5 mL) and the pH adjusted to 3 with 6 M HCl. The mixture was extracted with ethyl acetate (3×10 mL), and the combined organic extracts washed with brine (20 mL), dried over sodium sulfate and evaporated to give the title compound (I90) (39 mg, 85% yield) as a pale yellow syrup; 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.54 (d, J=8.4 Hz, 2H), 7.35-7.27 (m, 4H), 4.38 (d, J=10.1 Hz, 1H), 4.07-3.80 (m, 5H), 3.67 (td, J=11.7, 2.7 Hz, 1H), 3.06 (s, 4H), 2.84 (s, 2H), 1.47 (s, 9H). LCMS Method C: rt 6.49 min; m/z 587.1 [M+H]+, 531.0 [M−tBu+2H]+, 487.1 [M-Boc+2H]+; m/z 585.2 [M−H]+.

후처리

  1. concentrationAfter 18 hours the mixture was concentrated
  2. additiondiluted with water (5 mL)
  3. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
  4. washthe combined organic extracts washed with brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. customevaporated

출처 및 근거

ORD 기록
ord-0e0ba08a929149438c514cb68cfae6f8
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012461B2

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