Methyl iodide → 1-methyl-2-methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one

HRID 705958Notes

Reaction equation

HRID 705958 reaction equation
[CH3:1][S:2][C:3]1[NH:4][CH:5]=[C:6]([CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[N:15][CH:16]=2)[C:7](=[O:9])[N:8]=1.[CH3:17]I>C1COCC1.[H-].[Na+]>[CH3:17][N:4]1[CH:5]=[C:6]([CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[N:15][CH:16]=2)[C:7](=[O:9])[N:8]=[C:3]1[S:2][CH3:1]

Participants

5

Reactant 2

HCID 6328Methyl iodideHCID 178503543HCID 178503543, compound

Product 1

HCID 677748841-methyl-2-methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-oneYield 48.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 24758Sodium hydrideSolvent

Procedure

2-Methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one (50 mg, 0.213 mmol, 1 eq) was dissolved in dry THF (0.7 ml) and NaH, 60% (24.7 mg, 0.618 mmol, 2.9 eq) was added. After 30 min, the reaction mixture was treated with methyl iodide (133 μl, 2.13 mmol, 10 eq) and was stirred overnight. After overnight the excess NaH was quenched by a slow addition of water, diluted with brine (30 ml) and extracted with Et2O (3×20 ml). Combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated to give a crude residue. Crude residue was purified via Biotage SP-1 Snap Si 10 g; 15 ml/min in the gradient of MeoH in DCM: 1% for 1 CV then from 1-5% for 20 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product 1-methyl-2-methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one (25.5 mg, yield=47.4%, purity=98%). [M+H]+=249.31 1H NMR (300 MHz; DMSO-d6) δ/ppm 2.49 (s, 3H), 3.53 (s, 3H), 3.58 (s, 2H), 7.80 (s, 1H), 8.72 (s, 2H), 9.03 (s, 1H)

Workup

  1. customAfter overnight the excess NaH was quenched by a slow addition of water
  2. additiondiluted with brine (30 ml)
  3. extractionextracted with Et2O (3×20 ml)
  4. dry with materialCombined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give a crude residue
  8. customCrude residue was purified via Biotage SP-1 Snap Si 10 g
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-2ec50e5dace84df49fc798ec43ff0f21
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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