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

HRID 525713ノート

反応式

HRID 525713 の反応式
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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
140 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f4f2f51b69584915a0e2659bca195ab1
出典データセット
uspto-grants-2016_05
特許番号
US09340537B2

反応ノート

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