Formic Acid → (7-Bromo-1,5-naphthyridin-3-yl)acetaldehyde

HRID 1271383Notes

Reaction equation

HRID 1271383 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[C:7]([CH:12]=[CH:13][O:14]CC)[CH:6]=2.C(O)=O>ClCCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH2:12][CH:13]=[O:14])[CH:8]=[N:9]2)=[N:4][CH:3]=1

Participants

4

Reactant 2

HCID 284Formic AcidHCID 670823433-Bromo-7-[2-ethoxyvinyl]-1,5-naphthyridine

Product 1

HCID 21043926(7-Bromo-1,5-naphthyridin-3-yl)acetaldehyde

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1,5-Naphthyridines of formula (53), wherein L2, R4, R5 and R6 are as defined in formula (I), can be prepared as described in Scheme 10. 3,7-Dibromo-[1,5]naphthyridine, prepared as described by W. W. Paudler, J. Org. Chem., 33:1384 (1968), can be treated with (2-ethoxyvinyl)tributylstannane, a halide source, such as, but not limited to, tetraethylammonium chloride, and a palladium source, such as, but not limited to, dichlorobis(triphenylphosphine)palladium (II) in a solvent, such as, but not limited to, N,N-dimethylformamide with heat (about 50° C. to about 150° C.) to provide 3-bromo-7-[2-ethoxyvinyl]-1,5-naphthyridine. 3-Bromo-7-[2-ethoxyvinyl]-1,5-naphthyridine can be treated with an acid, such as, but not limited to, formic acid at about 0° C. to about 60° C. in a solvent, such as, but not limited to, 1,2-dichloroethane to provide (7-bromo-1,5-naphthyridin-3-yl)acetaldehyde. Alternatively, 3-bromo-7-[2-ethoxyvinyl]-1,5-naphthyridine in a solvent, such as, but not limited to, tetrahydrofuran can be treated with an aqueous acid, such as, but not limited to, hydrochloric acid at about 0° C. to about 60° C. to provide (7-bromo-1,5-naphthyridin-3-yl)acetaldehyde. (7-Bromo-1,5-naphthyridin-3-yl)acetaldehyde can be treated with an amine of formula (5) under reductive amination conditions, such as, but not limited to, sodium triacetoxyborohydride and an acid, such as, but not limited to, acetic acid in a solvent, such as, but not limited to, 1,2-dichloroethane at about 0° C. to about 50° C. to provide amines of formula (52). Amines of formula (52) can be processed as described in Schemes 1–3 to provide 1,5-naphthyridines of formula (53).

Sources & evidence

ORD record
ord-36e8c90ceadf4c669465d4a395c8b121
Source dataset
uspto-grants-2007_04
Patent number
US07205316B2

Reaction notes

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