Water → N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3,3-difluoropyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

HRID 525713Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 525713
Cl.[F:2][C:3]1([F:8])[CH2:7][CH2:6][NH:5][CH2:4]1.CCN(C(C)C)C(C)C.Cl[C:19]1[C:38]([C:39]2[NH:43][N:42]=[CH:41][CH:40]=2)=[CH:37][C:22]([C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]([Cl:36])([F:35])[F:34])=[CH:28][CH:27]=2)=[O:24])=[CH:21][N:20]=1.O>CC(O)C>[Cl:36][C:33]([F:34])([F:35])[O:32][C:29]1[CH:28]=[CH:27][C:26]([NH:25][C:23](=[O:24])[C:22]2[CH:37]=[C:38]([C:39]3[NH:43][N:42]=[CH:41][CH:40]=3)[C:19]([N:5]3[CH2:6][CH2:7][C:3]([F:8])([F:2])[CH2:4]3)=[N:20][CH:21]=2)=[CH:31][CH:30]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 722015896-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

Produkt 1

HCID 118044890N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3,3-difluoropyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

3,3-Difluoropyrrolidine hydrochloride (69.8 mg, 0.486 mmol) and DIPEA (0.170 mL, 0.972 mmol) were added to 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide (Stage 48.1, 100 mg, 0.243 mmol) in iPrOH (0.5 mL) and stirred at 140° C. for 3 h. The RM was treated with water, and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude material which was purified by crystallization from DCM/EtOAc to give the title product as a white solid. HPLC (Condition 7) tR=6.746 min, UPLC-MS (Condition 3) tR=1.11 min, m/z=470.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.32-2.45 (m, 2H) 3.42-3.51 (m, 2H) 3.56 (t, J=13.29 Hz, 2H) 6.48 (s, 1H) 7.34 (d, J=8.60 Hz, 2H) 7.73-7.88 (m, 3H) 8.13 (d, J=2.35 Hz, 1H) 8.79 (s, 1H) 10.30 (s, 1H) 13.01 (br.s, 1H).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. dry with materialThe combined extracts were dried over Na2SO4
  3. customthe solvent was evaporated off under reduced pressure
  4. customto give the crude material which
  5. customwas purified by crystallization from DCM/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-f4f2f51b69584915a0e2659bca195ab1
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340537B2

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