2-Chloro-3,6-difluorophenol → 4-(2-Chloro-3,6-difluoro-phenoxy)-6-[6-(4-methylpiperazin-1-yl)-pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridine

HRID 659456Notes

Reaction equation

HRID 659456 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[CH:12][C:11]([C:14]3[CH:15]=[C:16]4[C:21](=[N:22][CH:23]=3)[NH:20][CH2:19][CH2:18][CH:17]4[OH:24])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[Cl:25][C:26]1[C:31]([F:32])=[CH:30][CH:29]=[C:28]([F:33])[C:27]=1O>CO.C(Cl)Cl>[Cl:25][C:26]1[C:31]([F:32])=[CH:30][CH:29]=[C:28]([F:33])[C:27]=1[O:24][CH:17]1[C:16]2[C:21](=[N:22][CH:23]=[C:14]([C:11]3[CH:12]=[N:13][C:8]([N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:9][CH:10]=3)[CH:15]=2)[NH:20][CH2:19][CH2:18]1

Participants

4

Reactant 2

HCID 27735612-Chloro-3,6-difluorophenolHCID 578858296-[6-(4-Methylpiperazin-1-yl)pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridin-4-ol

Product 1

HCID 469066724-(2-Chloro-3,6-difluoro-phenoxy)-6-[6-(4-methylpiperazin-1-yl)-pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridineYield 54%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

6-[6-(4-Methylpiperazin-1-yl)pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridin-4-ol (85 mg) was reacted with 2-chloro-3,6-difluorophenol (50 mg) as in General Procedure 12. Silica gel chromatography using a gradient of 0-10% methanol/CH2Cl2 as the eluting solvent gave the title compound as a yellow foam (54% yield). LCMS: m/z=472 (M+H+), 1H-NMR (DMSO-d6, 400 MHz) δ 1.89 (m, 1H), 2.21 (s, 3H), 2.24 (m, 1H), 2.39 (t, J=4.8 Hz, 4H), 3.40 (m, 1H), 3.47 (t, J=4.8 Hz, 4H), 3.63 (m, 1H), 6.82 (d, J=8.8 Hz, 1H), 7.03 (d, J=2.3 Hz, 1H), 7.17 (d, J=2.3 Hz, 1H) 7.25 (m, 1H), 7.39 (m, 1H), 7.52 (dd, J=2.5, 8.8 Hz, 1H), 8.08 (d, J=2.5 Hz, 1H), 8.19 (d, J=2.5 Hz, 1H).

Sources & evidence

ORD record
ord-00bcef479afc4c05a546daec3fa9ec4e
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

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