Trifluoroacetic acid → 6-(1,2,3,4-Tetrahydro-isoquinolin-7-yloxy)-nicotinamide
Reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[CH:18][C:19]([O:25][C:26]3[CH:31]=[CH:30][C:29]([C:32](=[O:34])[NH2:33])=[CH:28][N:27]=3)=[CH:20][CH:21]=2)[CH2:16]1)=O)(C)(C)C>ClCCl>[CH2:16]1[C:17]2[C:22](=[CH:21][CH:20]=[C:19]([O:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([NH2:33])=[O:34])=[CH:28][N:27]=3)[CH:18]=2)[CH2:23][CH2:24][NH:15]1Participants
Procedure
Add drop wise via an addition funnel a solution of trifluoroacetic acid (3.3 mL) in dichloromethane (10 mL) to a stirred solution of 7-(5-carbamoyl-pyridin-2-yloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.2 g, 3.3 mmol)) in dichloromethane (50 mL) at 0° C. Warm to room temperature and stir for 18 hours. Evaporate on a rotary evaporator, dissolve the residue in methanol, and then apply in equal parts to 2-10 g SCX cartridges. Wash each cartridge with methanol until neutral pH then elute product with 2.0 M ammonia in methanol. Collect the basic eluent and concentrate on a rotary evaporator to yield 6-(1,2,3,4-tetrahydro-isoquinolin-7-yloxy)-nicotinamide (0.9 g, 3.3 mmol): 1H NMR (CDCl3, 300.00 MHz): 8.57 (s, 1H); 8.15 (d, 1H); 7.15-7.13 (m, 1H); 6.96-6.89 (m, 2H); 6.80 (s, 1H); 5.87 (br, 2H); 4.01 (s, 2H); 3.17-3.13 (m, 2H); 2.82-2.78 (m, 2H); 1.73 (br, 1H).
Workup
- customEvaporate on a rotary evaporator
- dissolutiondissolve the residue in methanol
- washWash each cartridge with methanol until neutral pH
- customCollect the basic eluent
- concentrationconcentrate on a rotary evaporator
Sources & evidence
- ORD record
- ord-84ea47b51dba4d69a558013bba5925b9
- Source dataset
- uspto-grants-2009_07
- Patent number
- US07560463B2
Reaction notes
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