2-(4-Methylpiperazin-1-yl)pyridine-4-boronic acid, pinacol ester → 4-(3-Chlorophenoxy)-6-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridine

HRID 659461Notes

Reaction equation

HRID 659461 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][CH2:7][CH2:6][CH:5]2[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=1.[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[C:31](B3OC(C)(C)C(C)(C)O3)[CH:30]=[CH:29][N:28]=2)[CH2:23][CH2:22]1>C(OCC)(=O)C.CCCCCC>[Cl:19][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[O:12][CH:5]1[C:4]2[C:9](=[N:10][CH:11]=[C:2]([C:31]3[CH:30]=[CH:29][N:28]=[C:27]([N:24]4[CH2:23][CH2:22][N:21]([CH3:20])[CH2:26][CH2:25]4)[CH:32]=3)[CH:3]=2)[NH:8][CH2:7][CH2:6]1

Participants

4

Reactant 2

HCID 27695372-(4-Methylpiperazin-1-yl)pyridine-4-boronic acid, pinacol esterHCID 578858956-Bromo-4-(3-chlorophenoxy)-1,2,3,4-tetrahydro-[1,8]naphthyridine

Product 1

HCID 578860864-(3-Chlorophenoxy)-6-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridineYield 36%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

6-Bromo-4-(3-chlorophenoxy)-1,2,3,4-tetrahydro-[1,8]naphthyridine (20 mg) was reacted with 1-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl]piperazine (25 mg) as in General Procedure 13. Silica gel chromatography using a gradient of 0-100% ethyl acetate/hexane as the eluting solvent gave the title compound as a white foam (36% yield). LCMS: m/z=436.06 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.0-2.11 (m, 1H), 2.24-2.40 (m, 1H), 2.35 (s, 3H), 2.54 (t, J=4.9 Hz, 4H), 3.4-3.51 (m, 1H), 3.57-3.68 (m, 5H), 5.27 (bs, 1H), 5.38 (t, J=3.4 Hz, 1H), 6.64 (s, 1H), 6.73 (dd, J=1.0 and 5.2 Hz, 1H), 6.90 (dd, J=2.2 and 8.3 Hz, 1H), 6.95-7.03 (m, 1H), 7.04-7.08 (m, 1H), 7.22-7.28 (m, 1H), 7.57 (d, J=1.9 Hz, 1H), 8.17 (d, J=5.2 Hz, 1H), 8.31 (d, J=2.2 Hz).

Sources & evidence

ORD record
ord-ecbd18455a554a288d3be4a19125ab39
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

Loading…