Ethanol → 2-(1,1-Dioxothiazinan-2-yl)-N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide

HRID 720285Notes

Reaction equation

HRID 720285 reaction equation
C(O[C:4]([C:6]1[N:7]=[C:8]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][S:16]2(=[O:22])=[O:21])[N:9]([CH3:14])[C:10](=[O:13])[C:11]=1[OH:12])=[O:5])C.[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=1.C(O)C>CN(C)C=O>[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH:29][C:4]([C:6]2[N:7]=[C:8]([N:15]3[CH2:20][CH2:19][CH2:18][CH2:17][S:16]3(=[O:21])=[O:22])[N:9]([CH3:14])[C:10](=[O:13])[C:11]=2[OH:12])=[O:5])=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 673264-FluorobenzylamineHCID 58739067HCID 58739067, compound

Product 1

HCID 546820402-(1,1-Dioxothiazinan-2-yl)-N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamideYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid ethyl ester (1.00 g, 3.02 mmol) and 4-fluorobenzylamine (1.31 g, 10.5 mmol) in a mixture of anhydrous ethyl alcohol (40 ml) and N,N-dimethylformamide (10 ml) was heated under reflux for 10 h. The solvent was then evaporated in vacuo and the residue was diluted with dichloromethane (500 ml). The organic phase was washed with 5% aqueous acetic acid, brine and dried over anhydrous sodium sulfate. Evaporation of the solvent and recrystallization of the white solid obtained from dichloromethane and ethanol gave 1.04 g (84% yield) of the title amide as white crystals; mp 227–228° C. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.75 and 2.07 (2×1H, m, CH2), 2.28–2.43 (2H, m, CH2), 3.19–3.31 (2H, m, CH2), 3.64 (3H, s, NCH3), 3.6–3.8 (2H, m, CH2), 4.59 (2H, AB part of ABX system, JAB=14.9 Hz, Δν=36.1 Hz, JAX=6.6 Hz, JBX=5.8 Hz, NCH2), 7.06 (2H, m, aromatics), 7.31 (2H, m, aromatics), 7.52 (1H, broad NH). Anal. Calcd for C17H19FN4O5S: C 49.75, H 4.67, N 13.65. Found: C 49.67, H 4.63, N 13.77.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 10 h
  3. customThe solvent was then evaporated in vacuo
  4. additionthe residue was diluted with dichloromethane (500 ml)
  5. washThe organic phase was washed with 5% aqueous acetic acid, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customEvaporation of the solvent and recrystallization of the white solid
  8. customobtained from dichloromethane and ethanol

Sources & evidence

ORD record
ord-2d3a411f6e9d4b089a9cbe77059acc69
Source dataset
uspto-grants-2006_11
Patent number
US07135467B2

Reaction notes

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