Trifluoroacetic acid → HCID 59730223, compound

HRID 228394Notes

Reaction equation

HRID 228394 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[O:25][C:26]2[CH:31]=[CH:30][C:29]([C:32](=[O:34])[NH2:33])=[CH:28][N:27]=2)[CH2:16]1)=O)(C)(C)C>ClCCl>[CH2:16]1[C:17]2[C:22](=[C:21]([O:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([NH2:33])=[O:34])=[CH:28][N:27]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:23][CH2:24][NH:15]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59730065HCID 59730065, compound

Product 1

HCID 59730223HCID 59730223, compoundYield 98.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add drop wise via an addition funnel a solution of trifluoroacetic acid (5.7 mL) in dichloromethane (25 mL) to a stirred solution of 5-(5-carbamoyl-pyridin-2-yloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (2.1 g, 5.7 mmol) in dichloromethane (75 mL) at 0° C. Warm to room temperature and stir for 18 hours. Evaporate on a rotary evaporator, dissolve the residue in methanol (50 mL) and dichloromethane (50 mL), and then add MP-carbonate resin (7.9 g @2.87 eq/g). Agitate for 2 hours, filter, concentrate on a rotary evaporator, and dry under vacuum to yield 6-(1,2,3,4-tetrahydro-isoquinolin-5-yloxy)-nicotinamide (1.5 g, 5.6 mmol): HPLC=85% (50/50 to 90/10 ACN/(0.1% TFA in water), Zorbax SB-Phenyl 4.6 mm×15 cm×5 micron, λ=254 nm). 1H NMR (DMSO-d6, 300.00 MHz): 8.55 (d, 1H), 8.23 (dd, 1H), 8.01 (s, 1H), 7.46 (s, 1H), 6.95 (m, 5H), 3.90 (s, 2H), 2.85 (m, 2H), 2.38 (m, 2H).

Workup

  1. customEvaporate on a rotary evaporator
  2. dissolutiondissolve the residue in methanol (50 mL)
  3. stirringAgitate for 2 hours
  4. filtrationfilter
  5. concentrationconcentrate on a rotary evaporator
  6. customdry under vacuum

Sources & evidence

ORD record
ord-50eb08523d844e11a015d046ed523983
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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