o-Fluorobenzaldehyde → 5-[(2-Fluorophenyl)hydroxymethyl]-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

5-Bromo-1-isobutyl-3-methyl-6-[2-(trifluoromethyl)benzyl]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (Example 1 part c)) (100 mg) was dissolved in tetrahydrofuran (2 ml) and EtMgBr (210 ul of a 1M solution in tetrahydrofuran) was added. After 10 min 2-fluorobenzaldehyde (210 μl of a 1M solution in tetrahydrofuran) was added. After 1 hr the reaction was quenched via addition of water. The reaction was concentrated in vacuo and extracted into dichloromethane, concentrated in vacuo and purified by chromatography eluting with 0-75% diethyl ether in isohexane to yield 5-[(2-fluorophenyl)hydroxymethyl]-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione. This was redissolved in dichloromethane (1 ml) and added to a mixture of oxalyl chloride (50 ul) and dimethyl sulphoxide (100 μl) in dichloromethane (1 ml) at −78° C. After 30 mins triethylamine (260 ul) was added and the reaction allowed to warm to room temperature. The reaction was then washed with water and evaporated to dryness before the residue was purified by chromatography eluting with 0-75% diethyl ether in hexane to yield the title compound (11 mg).

Provenance & Evidence