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

HRID 1805751Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]([NH2:10])=[O:9])=[C:6]([Cl:11])[N:5]=[C:4]([Cl:12])[CH:3]=1.[CH2:13](OC(OCC)OCC)C>>[Cl:11][C:6]1[C:7]2[C:8](=[O:9])[NH:10][CH:13]=[N:1][C:2]=2[CH:3]=[C:4]([Cl:12])[N:5]=1

Participants

Reactant 2

HCID 31214Ethyl orthoformate

HCID 580930524-Amino-2,6-dichloronicotinamide

Product 1

HCID 1357415885,7-Dichloropyrido[4,3-d]pyrimidin-4(3H)-one

Procedure

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).

Sources & evidence

ORD record: ord-233a5c42d95a4cb086ee780d890a5cef
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354526B2

Reaction notes

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