4'-Fluoro-2'-hydroxyacetophenone → 1-(4-Fluoro-2-{6-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1,2,3,4-tetrahydro-[1,8]naphthyridin-4-yloxy}phenyl)ethanone

HRID 659460Notes

Reaction equation

HRID 659460 reaction equation
[OH:1][CH:2]1[CH2:11][CH2:10][NH:9][C:8]2[N:7]=[CH:6][C:5]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)=[O:19])=[CH:14][CH:13]=3)=[CH:4][C:3]1=2.[F:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[C:30](O)[CH:29]=1>CO.C(Cl)Cl>[F:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[C:30]([O:1][CH:2]2[C:3]3[C:8](=[N:7][CH:6]=[C:5]([C:12]4[CH:13]=[CH:14][C:15]([C:18]([N:20]5[CH2:21][CH2:22][N:23]([CH3:26])[CH2:24][CH2:25]5)=[O:19])=[CH:16][CH:17]=4)[CH:4]=3)[NH:9][CH2:10][CH2:11]2)[CH:29]=1

Participants

4

Reactant 2

HCID 27373264'-Fluoro-2'-hydroxyacetophenoneHCID 57886094[4-(5-Hydroxy-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)phenyl]-(4-methylpiperazin-1-yl)methanone

Product 1

HCID 578859961-(4-Fluoro-2-{6-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1,2,3,4-tetrahydro-[1,8]naphthyridin-4-yloxy}phenyl)ethanoneYield 53%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

[4-(5-Hydroxy-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)phenyl]-(4-methylpiperazin-1-yl)methanone (30 mg) was reacted with 1-(4-fluoro-2-hydroxyphenyl)ethanone (39.4 mg) as in General Procedure 12. Silica gel chromatography using a gradient of 0-15% methanol/CH2Cl2 as the eluting solvent gave the title compound as a yellow foam (53% yield). LCMS: m/z=489.14 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.11-2.25 (m, 2H), 2.32 (s, 3H), 2.32-2.58 (m, 4H), 2.45 (s, 3H), 3.40-3.68 (m, 4H), 3.70-3.90 (m, 2H), 5.31 (bs, 1H), 5.51 (t, J=3.3 Hz, 1H), 6.75-6.82 (m, 1H), 6.89 (dd, J=2.1 and 10.7 Hz, 1H), 7.41-7.51 (m, 4H), 7.57-7.61 (m, 1H), 7.80 (dd, J=7.1 and 8.6 Hz, 1H, 8.33 (bs, 1H).

Sources & evidence

ORD record
ord-48ff15bc841c453081d1e9e88f9c10ed
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

Loading…