N-bromobutanimide → 1-Bromo-4-hydroxy-7-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid butyl ester

HRID 706193Notes

Reaction equation

[CH2:1]([O:5][C:6]([C:8]1[N:9]=[CH:10][C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[Br:28]N1C(=O)CCC1=O>C(#N)C>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([Br:28])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solid mixture of 7-(4-methoxy-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (305 mg, 0.83 mmol) and N-bromosuccinimide (162 mg, 0.91 mmol) cooled with an ice bath was added acetonitrile (6 mL). Resulting mixture was stirred at 0° C. for 1.5 h and was concentrated. The residue was purified by silica gel chromatography (eluting with 10%-40% ethyl acetate in hexanes) to provide the title compound (217 mg). 1H NMR (200 MHz, CDCl3) δ 11.88 (s, 1H), 8.32 (d, J=9.0 Hz, 1H), 7.54 (d, J=2.4 Hz, 1H), 7.46 (dd, J=9.0, 2.4 Hz, 1H), 7.08 (d, J=9.4 Hz, 2H), 6.95 (d, J=9.8 Hz, 2H), 4.46 (t, J=7.0 Hz, 2H), 3.85 (s, 3H), 1.85 (m, 2H), 1.47 (m, 2H), 0.98 (t, J=7.4 Hz, 3H).

Workup

temperaturecooled with an ice bath
customResulting mixture
concentrationwas concentrated
customThe residue was purified by silica gel chromatography (eluting with 10%-40% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-385bf2dfb7994bd6b869254d0af61c78
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174976B2

Reaction notes

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