3,7-Dibromo-1,5-naphthyridine → 3-Bromo-7-[2-ethoxyvinyl]-1,5-naphthyridine

HRID 273203

Reaction equation

HRID 273203 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[C:7]([Br:12])[CH:6]=2.[CH2:13]([O:15][CH:16]=[CH:17][Sn](CCCC)(CCCC)CCCC)[CH3:14]>[Cl-].C([N+](CC)(CC)CC)C.[Pd].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[Br:12][C:7]1[CH:8]=[N:9][C:10]2[C:5]([CH:6]=1)=[N:4][CH:3]=[C:2]([CH:14]=[CH:13][O:15][CH2:16][CH3:17])[CH:11]=2

Participants

7

Reactant 2

HCID 12366583,7-Dibromo-1,5-naphthyridineHCID 2763294(Z)-1-Ethoxy-2-(tributylstannyl)ethene

Product 1

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

Reagents, catalysts & solvents 4

HCID 5946Tetraethylammonium ChlorideCatalystHCID 23938PalladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

1,5-Naphthyridines of formula (53), wherein R4 and R5 are as defined in formula (I) and R6 is aryl or heteroaryl, can be prepared as described in Scheme 7. 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 povide amines of formula (52). Amines of formula (52) can be treated with boronic acids of formula (7), a palladium source, such as, but not limited to, tris(dibenzylideneacetone)dipalladium (0), a ligand, such as, but not limited to, tri(tert-butyl)phosphine, and a base, such as, but not limited to, potassium fluoride in a solvent, such as, but not limited to, tetrahydrofuran at about 20° C. to about 80° C. to provide 1,5-naphthyridines of formula (53).

Workup

  1. customcan be prepared

Sources & evidence

ORD record
ord-a98946cf30cd446597174a363afd868d
Source dataset
uspto-grants-2008_11
Patent number
US07456196B2

Linked notes

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