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 2174296ノート

反応式

HRID 2174296 の反応式
[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

参加物

7

反応物 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

生成物 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)carbamate収率 81%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 22226298MeOH ACN DCM溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-14aaf7cea04549d4ac5bfca287644a9b
出典データセット
uspto-grants-2015_06
特許番号
US09061030B2

反応ノート

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