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 2174296Notes

Reaction equation

HRID 2174296 reaction equation
[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

Participants

7

Reactant 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

Product 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)carbamateYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22226298MeOH ACN DCMSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-14aaf7cea04549d4ac5bfca287644a9b
Source dataset
uspto-grants-2015_06
Patent number
US09061030B2

Reaction notes

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