Water → methyl 4,6-diamino-2-(1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazol-3-yl)pyrimidin-5-yl(methyl)carbamate

HRID 2174296노트

반응식

HRID 2174296 반응식
[NH2:1][C:2]1[C:7]([NH:8][C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([C:14]2[N:18]=[C:17]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)[N:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])[N:15]=2)[N:3]=1.[H-].[Na+].I[CH3:35].O>CN(C=O)C.CC#N.CO.C(Cl)Cl>[NH2:1][C:2]1[C:7]([N:8]([CH3:35])[C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([C:14]2[N:18]=[C:17]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)[N:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])[N:15]=2)[N:3]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69092853methyl 4,6-diamino-2-(1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazol-3-yl)pyrimidin-5-ylcarbamate

생성물 1

HCID 56968070methyl 4,6-diamino-2-(1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazol-3-yl)pyrimidin-5-yl(methyl)carbamate수율 81%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 22226298MeOH ACN DCM용매

실험 절차

A suspension of methyl 4,6-diamino-2-(1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazol-3-yl)pyrimidin-5-ylcarbamate (I-60, 0.16 mmol) in DMF (3.0 mL) at 0° C. was treated with sodium hydride (1.1 equiv). After 15 min, the reaction mixture was warmed to ambient temperature and stirred for 15 min. The reaction was cooled to 0° C. and iodomethane (1.1 equiv) was added. The resultant mixture was brought to ambient temperature and stirred for 20 min. Water was added and the aqueous mixture was extracted with EtOAc and iPrOH/CH2Cl2 (1:4). The organic phases were dried over Na2SO4, filtered, conc. and purified using SiO2 chromatography and an appropriate gradient (CH3CN/MeOH/CH2Cl2) to afford methyl 4,6-diamino-2-(1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazol-3-yl)pyrimidin-5-yl(methyl)carbamate as an off-white solid (81% yield).

후처리

  1. temperatureThe reaction was cooled to 0° C.
  2. customwas brought to ambient temperature
  3. stirringstirred for 20 min
  4. extractionthe aqueous mixture was extracted with EtOAc and iPrOH/CH2Cl2 (1:4)
  5. dry with materialThe organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. customconc. and purified

출처 및 근거

ORD 기록
ord-14aaf7cea04549d4ac5bfca287644a9b
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09061030B2

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