Water → HCID 58166428, compound

HRID 1405994Notes

Reaction equation

HRID 1405994 reaction equation
P(Cl)(Cl)(Cl)=O.[NH:6]1[CH:10]=[N:9][CH:8]=[N:7]1.C(N(CC)CC)C.[F:18][C:19]1[C:20](=O)[NH:21][C:22](=[O:29])[N:23]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH:24]=1.O>CC#N>[F:18][C:19]1[C:20]([N:6]2[CH:10]=[N:9][CH:8]=[N:7]2)=[N:21][C:22](=[O:29])[N:23]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH:24]=1

Participants

7

Reactant 5

HCID 962WaterHCID 8471Triethylamine2×HCID 92571H-1,2,4-TriazoleHCID 24813Phosphorus oxychlorideHCID 6857465-Fluoro-1-(2-methylpropyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 58166428HCID 58166428, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Phosphoryl trichloride (3.3 g, 21 mmol) was added to a solution of 1,2,4-triazole (6.7 g, 97 mmol) in CH3CN (53 mL) under nitrogen at room temperature. The mixture was cooled to 0° C., whereupon triethylamine (Et3N, 9.5 g, 92 mmol) was added dropwise followed by the addition of a solution of 5-fluoro-1-isobutylpyrimidine-2,4(1H,3H)-dione (2.0 g, 11 mmol) in CH3CN (30 mL). After stiffing for 1 h at room temperature, Et3N (3.6 g, 36 mmol) and then water (5 mL, 280 mmol) were added, and the reaction mixture was stirred for an additional 10 min. The crude reaction mixture was then concentrated in vacuo. Recrystallization from EtOAc/petroleum ether provided 5-fluoro-1-isobutyl-4-(1H-1,2,4-triazol-1-yl)pyrimidin-2(1H)-one (1.9 g, 74%) as an off white crystalline solid: mp 150-153° C.; 1H NMR (400 MHz, CDCl3) δ 9.26 (s, 1H), 8.23 (s, 1H), 7.84 (d, J=5.7 Hz, 1H), 3.79 (d, J=7.4 Hz, 2H), 2.28 (dt, J=13.7, 6.9 Hz, 1H), 1.02 (d, J=6.7 Hz, 6H); ESIMS m/z 238 ([M+H]+).

Workup

  1. additionwas added dropwise
  2. customThe crude reaction mixture
  3. concentrationwas then concentrated in vacuo
  4. customRecrystallization from EtOAc/petroleum ether

Sources & evidence

ORD record
ord-9e85e9cfcbb34c36b1489e009c541e60
Source dataset
uspto-grants-2014_12
Patent number
US08916579B2

Reaction notes

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