Benzylamine → HCID 178507216, compound

HRID 2287660Notes

Reaction equation

HRID 2287660 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]=1.[CH2:11](N)C1C=CC=CC=1.C([O-])([O-])OCC.C(OC(=O)C)(=O)C.[SH-:32]>C(O)=O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:9](=[S:32])[NH:10][CH:11]=[N:8][C:6]=2[CH:7]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 2958964,6-DiaminonicotinonitrileHCID 5047209HydrosulfideHCID 86583744Ethyl orthoformate acetic anhydride

Product 1

HCID 178507216HCID 178507216, compound

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

2,4-Diamino-5-cyanopyridine can be cyclized directly to many 4-benzylamipnopyridopyrimidine derivatives by treatment with the benzylamine and formic acid at high temperature. For less nucleophilic amines 2,4-diamino-5-cyanopyridine is converted via ethyl orthoformate/acetic anhydride treatment, followed by cyclization with hydrosulfide ion in anhydrous conditions, to give 7-amino-4-thiono-3H-pyrido[4,3-d]pyrimidine. S-Alkylation and displacement with an appropriate amine gives the desired product. If R4 is not amino, the amine can be acylated, or reductively alkylated. Alternatively 2,4-diamino-5-cyanopyridine can be hydrolysed to the corresponding amide, and this species can be cyclized to 7-amino-4-oxo-3H-pyrido[4,3-d]pyrimidine with orthoformate. Diazotization of the 7-amine and replacement with fluorine allows for introduction of other amine and alkoxide nucleophiles at the end of the synthesis after the C4 substituent has been introduced in the usual manner. Diazotization and replacement of the amine with bromide allows for Stille couplings at the 7-position.

Sources & evidence

ORD record
ord-4e9eb4c145eb4ae6b3cbc98cd27cc5f9
Source dataset
uspto-grants-2000_07
Patent number
US06084095

Reaction notes

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