Chlorosuccinimide → N-[1-Cyano-2-(3,6-dichloro-2H-indazol-2-yl)-1-methylethyl]-4-trifluoromethoxybenzamide

HRID 1257043Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH2:11][C:12]([NH:16][C:17](=[O:29])[C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=1)([C:14]#[N:15])[CH3:13])[CH:6]=2.[Cl:30]N1C(=O)CCC1=O>C(#N)C.O>[C:14]([C:12]([NH:16][C:17](=[O:29])[C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]([F:26])([F:27])[F:28])=[CH:20][CH:19]=1)([CH3:13])[CH2:11][N:7]1[C:6]([Cl:30])=[C:5]2[C:9]([CH:10]=[C:2]([Cl:1])[CH:3]=[CH:4]2)=[N:8]1)#[N:15]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of N-[2-(6-chloro-2H-indazol-2-yl)-1-cyano-1-methylethyl]-4-trifluoromethoxybenzamide (50 mg, described in Example 143), and N-chlorosuccinimide (16 mg) in acetonitrile (1 mL) was heated to 60° C. for 3.5 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was collected, dried over sodium sulfate, filtered and concentrated under reduced pressure to give a residue that was purified by chromatography (SiO2, heptane/EA) to afford the title compound (46 mg, 85%). MS (ES): M/Z [M+H]=457. 1H NMR: (400 MHz, CHLOROFORM-d): 1.92 (s, 3H), 4.80 (d, J=14.3 Hz, 1H), 5.03 (d, J=14.3 Hz, 1H), 7.15 (dd, J=9.0, 1.4 Hz, 1H), 7.35 (d, J=8.5 Hz, 2H), 7.57 (d, J=9.0 Hz, 1H), 7.63 (s, 1H), 7.93 (d, J=8.7 Hz, 2H) and 8.65 (s, 1H). 19F NMR (376 MHz, CHLOROFORM-d): −58.1 (s, 3F).

Workup

temperatureThe mixture was cooled to room temperature
extractionextracted with ethyl acetate
customThe organic layer was collected
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customto give a residue that
customwas purified by chromatography (SiO2, heptane/EA)

Sources & evidence

ORD record: ord-05b5f042d9c1485e8c381d41665ed190
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461176B2

Reaction notes

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