Tetrahydrofuran → (R)-4-(3-Hydroxypyrrolidin-1-yl)-3-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

HRID 73725노트

반응식

HRID 73725 반응식
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:26]=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)=[O:12])=[CH:9][C:8]=2[C:27]2[N:31](COCC[Si](C)(C)C)[N:30]=[CH:29][CH:28]=2)[CH2:3]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CCOC(C)=O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:26]=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:22])([F:23])[F:24])=[CH:18][CH:19]=3)=[O:12])=[CH:9][C:8]=2[C:27]2[NH:31][N:30]=[CH:29][CH:28]=2)[CH2:3]1

참가 물질

5

반응물 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 86702590(R)-4-(3-Hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)benzamide

생성물 1

HCID 72544441(R)-4-(3-Hydroxypyrrolidin-1-yl)-3-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

(R)-4-(3-Hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)benzamide (Stage 1.1, 149 mg, 0.2 mmol) was added to a MW vial, which was sealed and flushed with argon. A solution of 1 M TBAF in THF (2.98 mL, 2.98 mmol) was then added and the RM was stirred at 80° C. for 3 days. The RM was diluted with EtOAc (40 mL), washed with sat. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The crude product was purified by preparative SFC (Column DEAP, from 25% to 30% in 6 min) to yield the title compound as a white solid. UPLC-MS (Condition 3) tR=0.98 min, m/z=433.3 [M+H]+, m/z=431.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.75 (br. s, 1H) 1.86 (br. s, 1H) 2.70-2.79 (m, 1H) 3.03-3.19 (m, 2H) 3.19-3.28 (m, 1H) 4.20 (br. s, 1H) 4.73-4.92 (m, 1H) 6.34 (d, J=11.00 Hz, 1H) 6.73-6.94 (m, 1H) 7.32 (d, J=8.80 Hz, 2H) 7.65 (d, J=104.42 Hz, 1H) 7.81-7.96 (m, 4H) 10.10 (s, 1H) 12.88 (d, J=81.67 Hz, 1H).

후처리

  1. customwas sealed
  2. customflushed with argon
  3. washwashed with sat. NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customThe crude product was purified by preparative SFC (Column DEAP, from 25% to 30% in 6 min)

출처 및 근거

ORD 기록
ord-9b0cd09c828242a3878995d09cf2c3c0
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829195B2

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