4-Methoxybenzylamine → Ethyl 8-bromo-4-((4-methoxybenzyl)amino)quinoline-3-carboxylate

HRID 1469738Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:7]2Cl.[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][NH2:25])=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:7]2[NH:25][CH2:24][C:23]1[CH:26]=[CH:27][C:20]([O:19][CH3:18])=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of ethyl 8-bromo-4-chloroquinoline-3-carboxylate (1.8 g, 5.72 mmol) in DMF (10 mL) were added p-methoxybenzyl amine (860 mg, 6.27 mmol) and DIPEA (2.22 g, 17.21 mmol) and the reaction mixture was heated at 120° C. for 4 h. Then the reaction mixture was quenched with water and was extracted with EtOAc. The organic layer was washed with brine, separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 1.2 g of the title product. 1H NMR (300 MHz, DMSO d6): δ 9.11 (br s, 1H), 8.89 (s, 1H), 8.46-8.43 (d, J=8.7 Hz, 1H), 8.12-8.09 (d, J=7.8 Hz, 1H), 7.38-7.33 (t, J=8.4 Hz, 1H), 7.27-7.24 (d, J=8.4 Hz, 2H), 6.91-6.89 (d, J=8.1 Hz, 2H), 8.17 (d, 2H), 4.26-4.24 (q, J=7.2, 14.1 Hz, 2H), 3.72 (s, 3H), 1.29-1.24 (t, J=6.9 Hz, 3H).

Workup

customThen the reaction mixture was quenched with water
extractionwas extracted with EtOAc
washThe organic layer was washed with brine
customseparated
customdried
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography

Sources & evidence

ORD record: ord-f669daa21db24cfb826459df26f2f1ab
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006257B2

Reaction notes

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