Sodium Hydroxide → 1-(6-chloro-2,3-dimethyl-4-quinolinyl)-6-(1H-pyrazol-4-yl)-1H-indol-4-ol

HRID 1618600Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 6-chloro-4-(4-methoxy-6-(1H-pyrazol-4-yl)-1H-indol-1-yl)-2,3-dimethylquinoline (0.1059 g, 0.272 mmol) in DCM (2.7 mL) in ice bath was added 1M BBr3 in DCM (0.82 mL, 0.815 mmol) dropwise. The mixture was stirred at 0° C. for 1 h and at rt. After 26 h, to the mixture was added ice water and the mixture was neutralized with 10N NaOH to pH 9.0. The resulting solid was filtered to give a brown solid. The brown solid was purified by column chromatography on a silica gel column using 0 to 100% gradient of EtOAc in hexane as eluent to give 1-(6-chloro-2,3-dimethyl-4-quinolinyl)-6-(1H-pyrazol-4-yl)-1H-indol-4-ol as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ ppm 12.74 (1H, br. s.), 9.74 (1H, s), 8.08 (1H, d, J=8.8 Hz), 7.94 (1H, br. s.), 7.73 (1H, dd, J=8.9, 2.3 Hz), 7.68 (1H, br. s.), 7.33 (1H, d, J=3.4 Hz), 6.94 (1H, d, J=2.2 Hz), 6.87 (1H, d, J=3.2 Hz), 6.76 (1H, s), 6.47 (1H, s), 2.77 (3H, s), 2.06 (3H, s); Mass Spectrum (ESI) m/e=389.0 (M+1).

Workup

waitAfter 26 h
filtrationThe resulting solid was filtered
customto give a brown solid
customThe brown solid was purified by column chromatography on a silica gel column

Sources & evidence

ORD record: ord-18214cf5a0544e7c940bf005a858d88d
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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