Ammonia → 2-(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetamide

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][C:18](OCC)=[O:19])[CH:13]=[N:14]2)=[N:9][CH:8]=1.[NH3:27].CO>>[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][C:18]([NH2:27])=[O:19])[CH:13]=[N:14]2)=[N:9][CH:8]=1

Participants

Reactant 3

HCID 222Ammonia

HCID 887Methanol

HCID 90416945Ethyl 2-(7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetate

Product 1

HCID 862968492-(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetamide

Procedure

Ethyl 2-(7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetate (1.95 g, 5.44 mmol) was treated with a solution of ammonia in MeOH (7 M, 30 mL, 245 mmol). The slurry was stirred at ambient temperature for 30 h. The resulting precipitate was filtered and washed with MeOH to give the title compound as a cream colored solid. The crude product was azeotrope dried with toluene to remove traces of ammonia then dried on high vacuum for 48 h to give the title compound (1.79 g, 82%) as a pure white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.81 (t, J=2.0 Hz, 2H), 8.21 (d, J=1.4 Hz, 1H), 7.88 (d, J=2.6 Hz, 1H), 7.75-7.58 (m, 2H), 7.50 (td, J=8.4, 10.7 Hz, 1H), 7.45-7.36 (m, 1H), 7.05 (br s, 1H), 5.34 (s, 2H), 3.66 (s, 2H). [M+H]=330.2.