7-Bromoisoquinolin-1-ol → 1-Oxo-1,2-dihydroisoquinoline-7-carbonitrile
Reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[Cu](C#N)[C:14]#[N:15]>CN(C)C=O.O>[O:12]=[C:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([C:14]#[N:15])[CH:11]=2)[CH:6]=[CH:7][NH:8]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 180 °C
Procedure
To a suspension of 7-bromoisoquinolin-1(2H)-one (70 g, 0.31 mol) in N,N-dimethylformamide (1 L) was added copper cyanide (56 g, 0.63 mol). The reaction was heated to 180° C. for 2 hours. The reaction was cooled to room temperature and was diluted with water (1 L). The solution was extracted with ethyl acetate (3×). The organics were dried over sodium sulfate, filtered, and concentrated to give crude 1-oxo-1,2-dihydroisoquinoline-7-carbonitrile (37 g). This crude material was taken up in ethanol (500 mL) and 1 N aqueous sodium hydroxide (400 mL) was added. The mixture was heated to reflux and stirred for 2 hours. The reaction was cooled to room temperature and the pH was adjusted to ˜2 with 1 N aqueous hydrochloric acid. The solids were collected by filtration, rinsed with water, and dried under vacuum to give the title compound (35 g, 85%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6, δ): 13.15 (br. s., 1H), 11.49 (s, 1H), 8.75 (s, 1H), 8.17-8.14 (m, 1H), 7.75 (d, 1H), 7.34-7.29 (m, 1H), 6.62 (d, 1H).
Workup
- temperatureThe reaction was cooled to room temperature
- extractionThe solution was extracted with ethyl acetate (3×)
- dry with materialThe organics were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-d0879a61752d40898e3a2f4ce8e6d402
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09181252B2
Reaction notes
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