2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → 6-[(2,4-Dichloro-5-thiazolyl)hydroxymethyl]-1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylic acid, ethyl ester

HRID 131626

Reaction equation

HRID 131626 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]2[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][S:11][C:5]=2[N:4]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:3]1=[O:21].[Cl:22][C:23]1[S:24][C:25]([CH:29]=[O:30])=[C:26]([Cl:28])[N:27]=1.CN1C(=O)N(C)CCC1.[Li+].CC([N-]C(C)C)C>C1COCC1.C(O)(=O)C>[Cl:22][C:23]1[S:24][C:25]([CH:29]([OH:30])[C:10]2[S:11][C:5]3[N:4]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:3](=[O:21])[N:2]([CH3:1])[C:7](=[O:8])[C:6]=3[C:9]=2[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:26]([Cl:28])[N:27]=1

Participants

7

Reactant 4

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 14886722,4-Dichloro-1,3-thiazole-5-carboxaldehydeHCID 2724682Lithium diisopropylamideHCID 5282568Ethyl 3-methyl-1-(2-methylpropyl)-2,4-dioxo-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 866035756-[(2,4-Dichloro-5-thiazolyl)hydroxymethyl]-1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylic acid, ethyl esterYield 18.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-methyl-1-(2-methylpropyl)-2,4-dioxo-1,2,3,4-tetrahydro-thieno[2,3-d]pyrimidine-5-carboxylate (1.5 g), 2,4-dichlorothiazole-5-carboxaldehyde (1.75 g) and DMPU (1.2 ml) in THF (25 ml) at −78° C., was added LDA (10 mmol). Acetic acid (3 ml) was added and the mixture allowed to warm to ambient temperature. The mixture was then partitioned between ethyl acetate and water, the organics were collected, dried over magnesium sulphate and concentrated to dryness. The residue was purified by normal phase chromatography (3:1 i-hexane:ethyl acetate) to give the sub-title compound as a yellow foam (0.45 g).

Workup

  1. customThe mixture was then partitioned between ethyl acetate and water
  2. customthe organics were collected
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by normal phase chromatography (3:1 i-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-03a4f0a480934016888a6fbafb905ed1
Source dataset
uspto-grants-2008_06
Patent number
US07384951B2

Linked notes

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