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

HRID 73725Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 73725
[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

Komponenten

5

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

(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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-9b0cd09c828242a3878995d09cf2c3c0
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829195B2

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