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

HRID 551521

반응식

HRID 551521 반응식
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

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 5946Tetraethylammonium Chloride촉매HCID 23938Palladium촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

실험 절차

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 provide 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).

후처리

  1. customcan be prepared

출처 및 근거

ORD 기록
ord-9db0dcec45f54a73a1342c46abd69eca
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07947711B2

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