Methyl formate → 5-(2-Methyl-pyrimidin-5-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one

HRID 705975Notes

Reaction equation

HRID 705975 reaction equation
[H-].[Na+].CO[C:5](=[O:15])[CH2:6][CH2:7][C:8]1[CH:9]=[N:10][C:11]([CH3:14])=[N:12][CH:13]=1.[CH:16](OC)=O.[NH2:20][C:21]([NH2:23])=[S:22]>COCCOC.C(OCC)C>[CH3:14][C:11]1[N:12]=[CH:13][C:8]([CH2:7][C:6]2[C:5](=[O:15])[NH:20][C:21](=[S:22])[NH:23][CH:16]=2)=[CH:9][N:10]=1

Participants

7

Reactant 4

HCID 7865Methyl formateHCID 24758Sodium hydrideHCID 2723790ThioureaHCID 677746633-(2-Methyl-pyrimidin-5-yl)-propionic acid methyl ester

Product 1

HCID 205833715-(2-Methyl-pyrimidin-5-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-oneYield 35.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To the suspension of NaH, 60% (1.3 eq, 130 mg) in 600 μl of dry 1,2-dimethoxyethane, under argon atmosphere was carefully added, via syringe, a solution of 3-(2-Methyl-pyrimidin-5-yl)-propionic acid methyl ester (450 mg, 2.5 mmol, 1 eq) and methyl formate (4 eq, 616 μl) in 3 ml of dry 1,2-dimethoxyethane. The resulting suspension was stirred overnight (16 hours) at room temperature. In the reaction mixture was then added 3 ml of dry diethyl ether. The resulting precipitate was collected; it was washed with 3 ml of diethyl ether and dried. It was dissolved in 4 ml of absolute ethanol, thiourea (1.5 eq, 285 mg) was added and the reaction mixture was stirred at reflux under argon atmosphere for 8 hours. Solvent was then evaporated, the rest was dissolved in 3 ml of water and pH value of the solution was adjusted to 4.5-5 using 3N HCl water solution. The resulting precipitate was collected, it was washed with water and dried to afford 5-(2-Methyl-pyrimidin-5-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (210 mg, yield=35.9%, purity=95%) in form of white powder. MS: [M+H]+=235.17 1H NMR (300 MHz; DMSO-d6) δ/ppm 2.54 (s, 3H), 3.50 (s, 2H), 7.48 (s, 1H), 8.55 (s, 2H), 12.38 (br.s., 2H)

Workup

  1. additionunder argon atmosphere was carefully added, via syringe
  2. customThe resulting precipitate was collected
  3. washit was washed with 3 ml of diethyl ether
  4. customdried
  5. dissolutionIt was dissolved in 4 ml of absolute ethanol
  6. stirringthe reaction mixture was stirred
  7. temperatureat reflux under argon atmosphere for 8 hours
  8. customSolvent was then evaporated
  9. dissolutionthe rest was dissolved in 3 ml of water
  10. customThe resulting precipitate was collected
  11. washit was washed with water
  12. customdried

Sources & evidence

ORD record
ord-d1035fcb9a264c61b58074de64b068d8
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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