Ethyl orthoformate → 5,7-Dichloropyrido[4,3-d]pyrimidin-4(3H)-one

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Reaction Steps

In scheme (VII), the tert-butyl 4-(tert-butoxycarbonylamino)-2,6-dichloronicotinate (3) the Boc groups are removed by treatment with trifluoracetic acid (TFA) in dichloromethane (DCM) at room temperature (60° C.) for 3 hours thereby forming the carboxylic acid, 4-amino-2,6-dichloronicotinic acid (7). Subsequent treatment with thionyl chloride under reflux conditions for 50 minutes gives the acid chloride, 4-amino-2,6-dichloronicotinoyl chloride (8). Treatment with of the acid chloride (8) with ammonia gives the amide, 4-amino-2,6-dichloronicotinamide (9). Heating the amide (9) with triethylorthoformate for 6 hours gives 5,7-dichloropyrido[4,3-d]pyrimidin-4(3H)-one (10), which is then used to obtain various compounds of Formula (I) as illustrated in scheme (VII).

Provenance & Evidence