Cesium carbonate → 6-((2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidin-5-yl)methoxy)quinolin-2(1H)-one

HRID 77466ノート

反応式

HRID 77466 の反応式
Cl.Cl[CH2:3][C:4]1[C:5]([O:21][CH3:22])=[N:6][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[CH:13][CH:12]=2)=[N:8][CH:9]=1.[OH:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[CH:28]=[CH:27]2.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[F:19][CH:18]([F:20])[O:17][C:14]1[CH:15]=[CH:16][C:11]([NH:10][C:7]2[N:6]=[C:5]([O:21][CH3:22])[C:4]([CH2:3][O:23][C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[NH:30][C:29](=[O:34])[CH:28]=[CH:27]4)=[CH:9][N:8]=2)=[CH:12][CH:13]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 1770652,6-DihydroxyquinolineHCID 866797525-(chloromethyl)-N-(4-(difluoromethoxy)phenyl)-4-methoxypyrimidin-2-amine hydrochloride

生成物 1

HCID 866797546-((2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidin-5-yl)methoxy)quinolin-2(1H)-one収率 46.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

A solution of 5-(chloromethyl)-N-(4-(difluoromethoxy)phenyl)-4-methoxypyrimidin-2-amine hydrochloride (0.14 g, 0.398 mmol) in DMF (1.5 mL) was added to a mixture of 6-hydroxyquinolin-2(1H)-one (0.08 g, 0.496 mmol) and Cs2CO3 (0.518 g, 1.590 mmol) in DMF (6.5 mL). The reaction mixture was stirred at room temperature for 18 h, then diluted with water and filtered. The filter cake was stirred in methanol/DCM (1:1) for 18 h, filtered, and dried to give 6-((2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidin-5-yl)methoxy)quinolin-2(1H)-one as a beige solid (0.082 g, 45%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.67 (s, 1H), 9.76 (s, 1H), 8.35 (s, 1H), 7.96-7.70 (m, 3H), 7.36-6.93 (m, 6H), 6.51 (d, J=9.5 Hz, 1H), 4.94 (s, 2H), 3.99 (s, 3H). LCMS: R.T.=0.82; [M+H]+=441.1.

後処理

  1. filtrationfiltered
  2. stirringThe filter cake was stirred in methanol/DCM (1:1) for 18 h
  3. filtrationfiltered
  4. customdried

出典と根拠

ORDレコード
ord-eca49926ad6248a0a832437d6127c888
出典データセット
uspto-grants-2014_09
特許番号
US08841301B2

反応ノート

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