Diisopropylamine → 1,2,3,4-Tetrahydro-6-[hydroxy[4-(2-pyridinyl)phenyl]methyl]-3-methyl-1-(1-methylethyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylic acid, ethyl ester

Lithium diisopropylamide, freshly made by adding n-buthyllithium (1.1 mL, 2.5M in hexanes) to a solution of diisopropylamine (0.46 mL) in dry tetrahydrofuran under nitrogen at 0° C. and stirring for 20 min, was added to a solution of 1,2,3,4-tetrahydro-3-methyl-1-(1-methylethyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylic acid, ethyl ester (0.7 g), 4-(2-pyridyl)benzaldehyde (0.52 g) and DMPU (057 mL) in dry tetrahydrofuran under nitrogen at −78° C. The reaction mixture was stirred at −78° C. for 4 hours then quenched with glacial acetic acid (10 mL) and allowed to reach room temperature. Water was added and the mixture was extracted with ethyl acetate (twice). The organics were washed with brine, dried over MgSO4 and concentrated under vacuum to give a brown oil which was purified by silica chromatography eluting with isohexane/ethyl acetate (1/1) to give the sub-title compound as a pale yellow foam (0.47 g).

1. stirringThe reaction mixture was stirred at −78° C. for 4 hours
2. customthen quenched with glacial acetic acid (10 mL)
3. customto reach room temperature
4. additionWater was added
5. extractionthe mixture was extracted with ethyl acetate (twice)
6. washThe organics were washed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated under vacuum
9. customto give a brown oil which
10. customwas purified by silica chromatography
11. washeluting with isohexane/ethyl acetate (1/1)

ORD record

ord-8d09faef37a64a08af2bfd629cc8a1e8

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07384951B2