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

HRID 705997Notes

Reaction equation

HRID 705997 reaction equation
[H-].[Na+].CO[C:5](=[O:16])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([O:14][CH3:15])[CH:9]=1.C(OC)=O.[NH2:21][C:22]([NH2:24])=[S:23].[CH2:25](N(CC)CC)C>COCCOC>[CH3:15][O:14][C:10]1[CH:9]=[C:8]([CH2:7][C:6]2[C:5](=[O:16])[NH:21][C:22](=[S:23])[NH:24][CH:25]=2)[CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 5

HCID 7865Methyl formateHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 2723790ThioureaHCID 142234703-(2-Methoxy-pyridin-4-yl)-propionic acid methyl ester

Product 1

HCID 866662275-(2-Methoxy-pyridin-4-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-oneYield 58.7%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a suspension of NaH, 60% dispersion on mineral oil (1.3 eq, 320 mg, 60%) in 1.5 ml of dry 1,2-dimethoxyethane under argon atmosphere was added a solution of 3-(2-methoxy-pyridin-4-yl)-propionic acid methyl ester (1.2 g, 6.14 mmol, 1 eq) and methyl formate (2 eq, 760 μl) in 8 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. Mother liquor was removed and in the rest was triturated once more with diethyl ether. The precipitate was dried and was dissolved in 10 ml of absolute ethanol, thiourea (1.5 eq, 700 mg) and triethylamine (1.1 eq, 936 μl) were 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 10 ml of water. pH of the solution was adjusted to 6-7 and the formed precipitate was collected by filtration and was dried to 5-(2-methoxy-pyridin-4-ylmethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (900 mg, yield=58.7%, purity=95%). MS: [M+H]+=250.15 1H NMR (300 MHz; DMSO-d6) δ/ppm 3.51 (s, 2H), 3.81 (s, 3H), 6.65 (s, 1H), 6.85 (dd, J=5.42 Hz, J=1.03 Hz 1H), 7.42 (s, 1H), 8.03 (d, J=5.42 Hz, 1H), 12.02-12.76 (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. customMother liquor was removed and in the rest
  5. customwas triturated once more with diethyl ether
  6. customThe precipitate was dried
  7. dissolutionwas dissolved in 10 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 10 ml of water
  12. filtrationthe formed precipitate was collected by filtration

Sources & evidence

ORD record
ord-b525ae7b01d34f2d99ecf2f20fcfee64
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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