Dimethylformamide → 2-Chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde

Participants

Reaction Steps

Scheme 2 shows the synthesis of intermediate (S)-1-(4-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one II from 4-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)morpholino VI. Treatment of VI with isopropylmagnesium chloride Grignard reagent followed by n-butyllithium at −10° C. was followed by addition of dimethylformamide and quenching with aqueous acid gave formylated intermediate 2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde IV (Example 4). Reductive amination of IV was effected by mixing IV with the oxalate salt of (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one V followed by a reducing agent, such as sodium triacetoxyborohydride (Method A), 2-picoline borane (Method B) or 5-Ethyl-2-methylpyridine borane to give II which was crystallized in toluene/heptane (Example 5) or Me-THF/heptane.

Provenance & Evidence