Triethyl orthoacetate → 1-{[3-(4-Fluorophenyl)isoxazol-5-yl]methyl}-2-methyl-1H-imidazo[4,5-c][1,5]naphthyridine

HRID 606079Notes

Reaction equation

[C:1](OCC)(OCC)(OCC)[CH3:2].[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:23]=[C:22]([CH2:24][NH:25][C:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][N:34]=4)[N:29]=[CH:28][C:27]=3[NH2:36])[O:21][N:20]=2)=[CH:15][CH:14]=1>C1(C)C=CC=CC=1.Cl.N1C=CC=CC=1>[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:23]=[C:22]([CH2:24][N:25]3[C:26]4[C:35]5[N:34]=[CH:33][CH:32]=[CH:31][C:30]=5[N:29]=[CH:28][C:27]=4[N:36]=[C:1]3[CH3:2])[O:21][N:20]=2)=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Triethyl orthoacetate (2.8 mL, 15.2 mmol) was added to a solution of N4-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}[1,5]naphthyridine-3,4-diamine (prepared in Part B of Example 12, 3.4 g, 10.1 mmol) and pyridine hydrochloride (0.023 g, 0.20 mmol) in toluene (100 mL), and the reaction was heated at 110° C. under a nitrogen atmosphere for 15.5 hours. The reaction mixture was then concentrated under reduced pressure, and the residue was dissolved in dichloromethane. The work-up and purification procedures described in Part D of Example 12 were followed with the modification that the silica column was eluted with 5% methanol in ethyl acetate. 1-{[3-(4-Fluorophenyl)isoxazol-5-yl]methyl}-2-methyl-1H-imidazo[4,5-c][1,5]naphthyridine (1.15 g) was obtained as a light gray solid.

Workup

concentrationThe reaction mixture was then concentrated under reduced pressure
dissolutionthe residue was dissolved in dichloromethane
customThe work-up and purification procedures
washwas eluted with 5% methanol in ethyl acetate

Sources & evidence

ORD record: ord-dd99e1e3d0144457aa8802d306e0ab0a
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915281B2

Reaction notes

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