Methyl formate → 5-(6-methoxy-pyridin-3-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one

HRID 705992Notes

Reaction equation

HRID 705992 reaction equation
[H-].[Na+].CO[C:5](=[O:16])[CH2:6][CH2:7][C:8]1[CH:9]=[N:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=1.[CH:17](OC)=O.[NH2:21][C:22]([NH2:24])=[S:23]>COCCOC>[CH3:15][O:14][C:11]1[N:10]=[CH:9][C:8]([CH2:7][C:6]2[C:5](=[O:16])[NH:21][C:22](=[S:23])[NH:24][CH:17]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 7865Methyl formateHCID 24758Sodium hydrideHCID 2723790ThioureaHCID 22009636Methyl 3-(2-methoxy-5-pyridyl)propionate

Product 1

HCID 866662255-(6-methoxy-pyridin-3-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-oneYield 49.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a suspension of NaH, 60% dispersion on mineral oil (1.3 eq, 110 mg, 60%) in 700 μl of dry 1,2-dimethoxyethane under argon atmosphere was added a solution of 3-(6-Methoxy-pyridin-3-yl)-propionic acid methyl ester (590 mg, 3.02 mmol, 1 eq) and methyl formate (2 eq, 380 μl) in 4 ml of dry 1,2-dimethoxyethane. The sealed mixture was stirred at room temperature for 16 hours (overnight). Solvent from the mixture was then evaporated. In the rest was added 15 ml of diethyl ether and using ultrasound bath the precipitate was formed. The liquor was removed and in the rest was triturated once more with diethyl ether. The precipitate was dried and was dissolved in 5 ml of absolute ethanol, thiourea (1.5 eq, 345 mg) was added and the resulting mixture was heated at 90° C. (temperature on display of heating device) for 2 hours. The solvent was evaporated and the rest was dissolved in 5 ml of water. pH of the solution was adjusted to 6-7 and the formed precipitate was collected by filtration and was dried to afford 5-(6-methoxy-pyridin-3-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (395 mg, yield=49.8%, purity=95%). MS: [M+H]+=250.18 1H NMR (300 MHz; DMSO-d6) δ/ppm 3.45 (s, 2H), 3.80 (s, 3H), 6.70 (d, J=8.36 Hz, 1H), 7.42 (s, 1H), 7.55 (dd, J=8.36 Hz, J=2.40 Hz, 1H), 8.05 (d, J=2.40 Hz, 1H), 12.10-12.60 (m, 2H)

Workup

  1. customSolvent from the mixture was then evaporated
  2. additionIn the rest was added 15 ml of diethyl ether
  3. customwas formed
  4. customThe liquor was removed and in the rest
  5. customwas triturated once more with diethyl ether
  6. customThe precipitate was dried
  7. dissolutionwas dissolved in 5 ml of absolute ethanol
  8. temperaturethe resulting mixture was heated at 90° C.
  9. temperature(temperature on display of heating device) for 2 hours
  10. customThe solvent was evaporated
  11. dissolutionthe rest was dissolved in 5 ml of water
  12. filtrationthe formed precipitate was collected by filtration
  13. customwas dried

Sources & evidence

ORD record
ord-160048f815994fd8bd1b3471776f0650
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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