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

HRID 525730ノート

反応式

HRID 525730 の反応式
Cl.[OH:2][CH:3]1[CH2:6][NH:5][CH2:4]1.CCN(C(C)C)C(C)C.Cl[C:17]1[C:36]([C:37]2[NH:41][N:40]=[CH:39][CH:38]=2)=[CH:35][C:20]([C:21]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]([Cl:34])([F:33])[F:32])=[CH:26][CH:25]=2)=[O:22])=[CH:19][N:18]=1.O>CC(O)C>[Cl:34][C:31]([F:32])([F:33])[O:30][C:27]1[CH:26]=[CH:25][C:24]([NH:23][C:21](=[O:22])[C:20]2[CH:35]=[C:36]([C:37]3[NH:41][N:40]=[CH:39][CH:38]=3)[C:17]([N:5]3[CH2:6][CH:3]([OH:2])[CH2:4]3)=[N:18][CH:19]=2)=[CH:29][CH:28]=1

参加物

6

反応物 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 722015896-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

生成物 1

HCID 89908255N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3-hydroxyazetidin-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-Hydroxyazetidine hydrochloride (53.2 mg, 0.486 mmol) and DIPEA (0.170 mL, 0.972 mmol) were added to a suspension of 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 the RM was heated at 140° C. for 3 h. The RM was treated with water, extracted with EtOAc, and the combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give. the crude product which was purified by flash chromatography (RediSep® Silica gel column, 24 g, DCM/MeOH 9:1) to give the title product as a yellow foam. HPLC (Condition 7) tR=5.518 min, UPLC-MS (Condition 3) tR=0.89 min, m/z=436 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.49-3.57 (m, 2H) 3.87-3.99 (m, 2H) 4.32-4.44 (m, 1H) 5.53 (br.s, 1H) 6.40 (br.s, 1H) 7.33 (d, J=8.60 Hz, 2H) 7.81-7.91 (m, 3H) 8.06 (d, J=2.35 Hz, 1H) 8.70 (br.s, 1H) 10.23 (s, 1H) 13.01 (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
  5. customthe crude product which was purified by flash chromatography (RediSep® Silica gel column, 24 g, DCM/MeOH 9:1)

出典と根拠

ORDレコード
ord-a1b26e148438417a8898cfd5125d4982
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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