Water → Methyl 6-[4,5-dichloro-2-methyl-1H-imidazol-1-ylmethyl]-1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylate

HRID 900734Notes

Reaction equation

HRID 900734 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([CH3:8])[NH:5][C:6]=1[Cl:7].[H-].[Na+].Br[CH2:12][C:13]1[S:28][C:16]2[N:17]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:18](=[O:23])[N:19]([CH3:22])[C:20](=[O:21])[C:15]=2[C:14]=1[C:29]([O:31][CH3:32])=[O:30].O>O1CCCC1>[Cl:1][C:2]1[N:3]=[C:4]([CH3:8])[N:5]([CH2:12][C:13]2[S:28][C:16]3[N:17]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:18](=[O:23])[N:19]([CH3:22])[C:20](=[O:21])[C:15]=3[C:14]=2[C:29]([O:31][CH3:32])=[O:30])[C:6]=1[Cl:7]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 3123904,5-Dichloro-2-methyl-1H-imidazoleHCID 16102871Methyl 6-bromomethyl-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 11453923Methyl 6-[4,5-dichloro-2-methyl-1H-imidazol-1-ylmethyl]-1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

4,5-Dichloro-2-methylimidazole (1.3 g) in dry tetrahydrofuran (20 ml) was added dropwise to a suspension of sodium hydride (0.34 g, 60%) in dry tetrahydrofuran (20 ml) at room temperature under nitrogen. After 15 min, a solution of the product of step b) (3.35 g) in dry tetrahydrofuran (20 ml) was added dropwise and the reaction was stirred for 3 h at room temperature. The solution was poured into water and extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash silica chromatography eluting with a gradient 50-100% ethyl acetate in isohexane to give the sub-title compound as a white solid (2.28 g).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe combined extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash silica chromatography
  6. washeluting with a gradient 50-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-58ecf96e520249329a4040dbea5d2383
Source dataset
uspto-grants-2008_04
Patent number
US07361660B2

Reaction notes

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