Benzoyl chloride → HCID 59490723, compound

HRID 2383472Notes

Reaction equation

HRID 2383472 reaction equation
FC(F)(F)C(O)=O.[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.[C:31](Cl)(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClCCl.CCN(C(C)C)C(C)C>[CH3:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][N:15]2[C:19]3[N:20]=[CH:21][C:22]4[CH2:23][CH:24]([NH:28][C:31](=[O:38])[C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[CH2:25][CH2:26][C:27]=4[C:18]=3[CH:17]=[N:16]2)=[CH:29][CH:30]=1

Participants

5

Reactant 2

HCID 7412Benzoyl chlorideHCID 67426214HCID 67426214, compound

Product 1

HCID 59490723HCID 59490723, compoundYield 53.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-ylamine trifluoroacetate salt (0.092 g, 0.21 mmol) in dichloromethane (5 mL) and Hunig's Base (0.20 mL) was added benzoyl chloride (50 μL, 0.43 mmol). The reaction mixture was shaken at room temperature for 1 hour. The solvent was then removed under reduced pressure and the residue partitioned between EtOAc and 1.0N NaOH. The organic layer was then separated, washed with brine (2×10 mL) and concentrated under reduced pressure to give a residue. The crude product was purified by reverse phase HPLC to give the desired product, N-(3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-yl)benzamide as an off-white solid (0.046 g, 51%). Alternatively the crude product could be used in the next step without any further purification. M.p.>65° C.; 400 MHz 1H NMR (DMSO-d6) δ: 8.50 (d, J=7.6 Hz, 1H), 8.03 (s, 1H), 7.95 (s, 1H), 7.87 (m, 2H), 7.48 (m, 3H), 7.17 (m, 2H), 6.85 (m, 2H), 5.53 (m, 2H), 4.30 (m, 1H), 3.70 (s, 3H), 3.24-3.13 (m, 3H), 2.95 (m, 1H), 2.16 (m, 1H), 1.99 (m, 1H); LCMS [M+H]: 413.

Workup

  1. customThe solvent was then removed under reduced pressure
  2. customthe residue partitioned between EtOAc and 1.0N NaOH
  3. customThe organic layer was then separated
  4. washwashed with brine (2×10 mL)
  5. concentrationconcentrated under reduced pressure
  6. customto give a residue
  7. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-868b384d73e5448ebf9efff688318b11
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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