Potassium Carbonate → 4-methyl-3-[2-methyl-4-(2-methyl-thiazol-4-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-benzoic acid methyl ester

HRID 2172612Notes

Reaction equation

HRID 2172612 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([OH:18])[N:13]=[C:12]2[CH3:19])[CH:5]=1.Cl.Cl[CH2:23][C:24]1[N:25]=[C:26]([CH3:29])[S:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][CH2:23][C:24]3[N:25]=[C:26]([CH3:29])[S:27][CH:28]=3)[N:13]=[C:12]2[CH3:19])[CH:5]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)HCID 1363878053-(4-hydroxy-2-methyl-6-oxo-6H-pyrimidin-1-yl)-4-methyl-benzoic acid methyl ester

Product 1

HCID 866862944-methyl-3-[2-methyl-4-(2-methyl-thiazol-4-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-benzoic acid methyl esterYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Intermediate 2 (530 mg, 1.93 mmol) in N,N-dimethylformamide (2 mL) was added 4-(chloromethyl)-2-methyl-1,3-thiazole HCl (354 mg, 1.93 mmol), potassium carbonate (666 mg, 4.82 mmol) and 18-crown-6 (50 mg). The slurry was heated at 60° C. for three hours. The reaction was returned to ambient temperature and partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The slurry was filtered and concentrated in vacuo. The crude material was purified using normal phase chromatography (ethyl acetate/heptane) to provide the alkylated product as a colorless oil. (120 mg, 16% yield). MS (M+H): 386

Workup

  1. customwas returned to ambient temperature
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe slurry was filtered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified

Sources & evidence

ORD record
ord-c68216d90efd478fa0590c2d6db2ae8d
Source dataset
uspto-grants-2015_06
Patent number
US09056110B2

Reaction notes

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