Potassium Cyanide → HCID 69128203, compound

HRID 1593080Notes

Reaction equation

Br[C:2]1[C:11]([NH:12][CH3:13])=[C:10]([F:14])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]([C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1)[C:7]2=[O:15].[C:25]([Cu])#[N:26].[C-]#N.[K+]>CN1C(=O)CCC1>[F:14][C:10]1[C:11]([NH:12][CH3:13])=[C:2]([C:25]#[N:26])[C:3]2[CH:4]=[CH:5][N:6]([C:16]3[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=3)[C:7](=[O:15])[C:8]=2[CH:9]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A 110 mg (0.28 mmol) portion of 5-Bromo-7-fluoro-6-methylamino-2-(4-nitro-phenyl)-2H-isoquinolin-1-one (Example 107) and 55 mg (2.2 equiv) of CuCN in 1.4 mL of NMP was heated to 200° C. for 2 h. After cooling to 50° C., 10 mL of 10% aq KCN was added, and mixture was stirred, filtered, washed with water and dried to give 123 mg (130%) of 7-Fluoro-6-methylamino-2-(4-nitro-phenyl)-1-oxo-1,2-dihydro-isoquinoline-5-carbonitrile. A 50 mg (0.15 mmol) portion of this 5-cyano material was reduced with 36 mg of Raney Nickel (Aldrich) in 1:1:2 water/AcOH/pyridine containing 58 mg of sodium hypophosphite. The reaction was then extracted 3 times with ethyl acetate, drying over Na2SO4 (anh.), and concentration in vacuo afforded 10 mg (20%) of the resulting aniline. This material was then coupled using the method described in Example 13 to give 7.8 mg (46%) of 5-chloro-N-[({4-[5-cyano-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2(1H)-yl]phenyl}amino)carbonyl]thiophene-2-sulfonamide. ES-MS (M+H)+=532.1 (Cl).

Workup

filtrationfiltered
washwashed with water
customdried

Sources & evidence

ORD record: ord-fbfa876953624e5690a635731fdfecf5
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07294635B2

Reaction notes

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