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

HRID 73725Notes

Reaction equation

HRID 73725 reaction equation
[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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(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).

Workup

  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)

Sources & evidence

ORD record
ord-9b0cd09c828242a3878995d09cf2c3c0
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

Loading…