Benzaldehyde → Trifluoroacetic acid

HRID 2383470Notes

Reaction equation

HRID 2383470 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][O:9][C:10]1[CH:30]=[CH:29][C:13]([CH2:14][N:15]2[C:19]3[N:20]=[CH:21][C:22]4[CH2:23][CH:24]([NH2:28])[CH2:25][CH2:26][C:27]=4[C:18]=3[CH:17]=[N:16]2)=[CH:12][CH:11]=1.CCN(C(C)C)C(C)C.[CH:40](=O)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC=CC=1.C(O)C>[CH2:40]([NH:28][CH:24]1[CH2:23][C:22]2[CH:21]=[N:20][C:19]3[N:15]([CH2:14][C:13]4[CH:12]=[CH:11][C:10]([O:9][CH3:8])=[CH:30][CH:29]=4)[N:16]=[CH:17][C:18]=3[C:27]=2[CH2:26][CH2:25]1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[C:3]([OH:5])([C:2]([F:7])([F:6])[F:1])=[O:4]

Participants

8

Reactant 4

HCID 240BenzaldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67426214HCID 67426214, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 59490853HCID 59490853, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-amine trifluoroacetate salt (0.094 g, 0.22 mmol) in toluene (3 mL) and ethanol (1 mL) was added Hunig's Base (0.11 mL, 0.66 mmol). The mixture was vortexed to ensure dissolution followed by the addition of benzaldehyde (22 μL, 0.22 mmol). The reaction mixture was heated at 100° C. for 2 hours followed by removal of solvent under reduced pressure. To the residue was added dichloromethane (10 mL), Hunig's Base (0.10 mL) followed by sodium triacetoxyborohydride (0.173 g, 0.66 mmol). The reaction mixture was shaken at room temperature for 65 hours. The reaction was quenched by addition of 1.5M NaOH (10 mL) and shaking it at room temperature for 1 hour. The organic layer was then separated, washed with brine (2×10 mL) and concentrated under reduced pressure to give the crude product. The crude product was purified by reverse phase HPLC to give the desired product, N-benzyl-3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-amine as a TFA salt and a pale yellow solid (0.045 g, 51%). Alternatively the crude product could be used in the next step without any further purification M.p.>178° C.; 400 MHz 1H NMR (DMSO-d6) δ: 9.07 (brs, 2H), 8.08 (s, 1H), 8.02 (s, 1H), 7.56-7.44 (m, 5H), 7.16 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 5.54 (s, 2H), 4.32 (t, J=6.0 Hz, 2H), 3.69 (s, 3H), 3.64 (m, 1H), 3.41 (m, 1H), 3.11 (m, 3H), 2.41 (m, 1H), 1.98 (m, 1H); LCMS [M+H]: 399.

Workup

  1. dissolutiondissolution
  2. customfollowed by removal of solvent under reduced pressure
  3. additionTo the residue was added dichloromethane (10 mL), Hunig's Base (0.10 mL)
  4. customThe reaction was quenched by addition of 1.5M NaOH (10 mL)
  5. stirringshaking it at room temperature for 1 hour
  6. customThe organic layer was then separated
  7. washwashed with brine (2×10 mL)
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product
  10. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d6e78f72ef3b482699dfa951f4d18d60
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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