2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → 1,2,3,4-Tetrahydro-6-[hydroxy(1-phenyl-1H-pyrazol-4-yl)methyl]-3-methyl-1-(1-methylethyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylic acid ethyl ester

HRID 131628

Reaction equation

HRID 131628 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:13](=[O:15])[N:12]([CH3:16])[C:11](=[O:17])[N:10]([CH:18]([CH3:20])[CH3:19])[C:9]=2[S:8][CH:7]=1)=[O:5])[CH3:2].[C:21]1([N:27]2[CH:31]=[C:30]([CH:32]=[O:33])[CH:29]=[N:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CN1CCCN(C)C1=O.[Li+].CC([N-]C(C)C)C>C1COCC1.O.C(O)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:13](=[O:15])[N:12]([CH3:16])[C:11](=[O:17])[N:10]([CH:18]([CH3:19])[CH3:20])[C:9]=2[S:8][C:7]=1[CH:32]([OH:33])[C:30]1[CH:29]=[N:28][N:27]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:31]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 9520891-Phenyl-1H-pyrazole-4-carbaldehydeHCID 2724682Lithium diisopropylamideHCID 16102858Ethyl 1-isopropyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 693098291,2,3,4-Tetrahydro-6-[hydroxy(1-phenyl-1H-pyrazol-4-yl)methyl]-3-methyl-1-(1-methylethyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylic acid ethyl esterYield 73.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,2,3,4-tetrahydro-3-methyl-1-(1-methylethyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylic acid ethyl ester (2.0 g), 1-phenyl-1H-pyrazole-4-carboxaldehyde (1.39 g) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.63 ml) in anhydrous THF (35 ml) was added a 2.0M solution of LDA (3.72 ml) at −78° C. under nitrogen and the resulting mixture stirred for 3 hr. Glacial acetic acid (1.5 ml) was added, the mixture allowed to warm to room temperature, diluted with water and extracted with ethyl acetate, the organic extracts washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography over silica, eluting with i-hexane/ethyl acetate (4:1) followed by i-hexane/ethyl acetate (1:1) to give the sub-title compound (2.32 g).

Workup

  1. extractionextracted with ethyl acetate
  2. washthe organic extracts washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography over silica
  7. washeluting with i-hexane/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-55a9774b0d4241e794af27f34858bb57
Source dataset
uspto-grants-2008_06
Patent number
US07384951B2

Linked notes

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