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

HRID 77466노트

반응식

HRID 77466 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매2회

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-eca49926ad6248a0a832437d6127c888
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841301B2

반응 노트

불러오는 중…