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 2174296Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2174296
[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

Komponenten

7

Edukt 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

Produkt 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)carbamateAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 22226298MeOH ACN DCMLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-14aaf7cea04549d4ac5bfca287644a9b
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09061030B2

Notizen zur Reaktion

Wird geladen…