Trifluoroacetic acid → 3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine

HRID 2383424Notes

Reaction equation

HRID 2383424 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][C:15]4[CH2:16][N:17](C(OC(C)(C)C)=O)[CH2:18][CH2:19][C:20]=4[C:11]=3[CH:10]=[N:9]2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][C:15]4[CH2:16][NH:17][CH2:18][CH2:19][C:20]=4[C:11]=3[CH:10]=[N:9]2)=[CH:28][CH:29]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59490551tert-butyl 3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxylate

Product 1

HCID 594904033-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridineYield 81.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxylate (3.5 g, 8.8 mmol) in dichloromethane (35 mL) at room temperature was added trifluoroacetic acid (5.04 g, 44.4 mmol) in a drop wise manner. The reaction mixture was stirred at room temperature for 5 hours. Once the reaction was complete the solvent was removed under reduced pressure and the resulting residue was triturated with diethyl ether to give a solid. The solid was filtered, washed with diethyl ether and dried under reduce pressure. The dried solid was then dissolved in water and basified with saturated Na2CO3 solution. The aqueous layer was extracted with 10% methanol in CH2Cl2 (3×150 mL). The organic extracts were combined, dried using sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The residue was triturated with hexane to afford the pure desired product 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine as a white solid (2.1 g, 80%). M.p.=96-102° C. 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.93 (s, 1H), 7.26 (d, J=8.4 Hz, 2H), 6.80 (d, J=8.4 Hz, 2H), 5.61 (s, 2H), 4.11 (s, 2H), 3.73 (s, 3H), 3.219 (t, J=6 Hz, 2H), 3.016 (t, J=6 Hz, 2H) LCMS [M+H]: 295.

Workup

  1. customwas removed under reduced pressure
  2. customthe resulting residue was triturated with diethyl ether
  3. customto give a solid
  4. filtrationThe solid was filtered
  5. washwashed with diethyl ether
  6. customdried
  7. dissolutionThe dried solid was then dissolved in water and basified with saturated Na2CO3 solution
  8. extractionThe aqueous layer was extracted with 10% methanol in CH2Cl2 (3×150 mL)
  9. customdried
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto give a residue
  13. customThe residue was triturated with hexane

Sources & evidence

ORD record
ord-6d2647d0bff2471b97a791fe8df1280b
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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