3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine → HCID 59490542, compound

HRID 2383440Notes

Reaction equation

HRID 2383440 reaction equation
[CH:1]1[C:13]2[C:12]3[CH2:11][CH2:10][N:9]([C:14]([NH:16][C:17]4[CH:18]=[C:19]([CH:25]=[CH:26][CH:27]=4)[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[O:15])[CH2:8][C:7]=3[CH:6]=[N:5][C:4]=2[NH:3][N:2]=1.COC1C=CC(CN2C3N=CC4CNCCC=4C=3C=N2)=CC=1>FC(F)(F)C(O)=O>[CH:1]1[C:13]2[C:12]3[CH2:11][CH2:10][N:9]([C:14]([NH:16][C:17]4[CH:18]=[C:19]([CH:25]=[CH:26][CH:27]=4)[C:20]([OH:22])=[O:21])=[O:15])[CH2:8][C:7]=3[CH:6]=[N:5][C:4]=2[NH:3][N:2]=1.[CH:1]1[C:13]2[C:12]3[CH2:11][CH2:10][N:9]([C:14]([NH:16][C:17]4[CH:18]=[C:19]([CH:25]=[CH:26][CH:27]=4)[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[O:15])[CH2:8][C:7]=3[CH:6]=[N:5][C:4]=2[NH:3][N:2]=1

Participants

5

Reactant 2

HCID 594904033-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridineHCID 59490542HCID 59490542, compound

Product 2

HCID 59490542HCID 59490542, compoundYield 83%HCID 59490683HCID 59490683, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Step-1: Synthesis of ethyl 3-(6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7-carboxamido)benzoate. Step (i): A solution of 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine (0.945 g, 3.21 mmol) in trifluoroacetic acid (10 mL) was heated at 65° C. for 16 hours. Once the reaction was complete the solvent was removed under reduced pressure to give a dark brown solid. The product was used in the next step without any further purification. Step (ii): To the dark brown solid was added dichloromethane (30 mL) and Hunig's Base (5 mL). The mixture was vortexed to ensure that the solid had dissolved, then cooled in an ice-bath followed by the addition of 3-isocyanato-benzoic acid ethyl ester (0.613 g) as a solution in anhydrous dichloromethane (10 mL) in a drop wise fashion. The reaction was then shaken at room temperature for 20 minutes. Once the reaction was complete water (20 mL) was added and the reaction mixture was then extracted with CH2Cl2 (60 mL). The organic extract was washed with brine (2×20 mL), dried using sodium sulfate, filtered and concentrated to give desired crude product. The crude product was then purified using flash column chromatography (SiO2, 80% EtOAc in hexanes) to give the pure desired product, ethyl 3-(6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7-carboxamido)benzoate (0.98 g, 83%) as a white solid. M.p. 184-186° C.; 1H NMR (400 MHz, DMSO-d6) δ13.59 (s, 1H), 8.97 (s, 1H), 8.35 (s, 1H), 8.17 (s, 1H), 8.13 (t, J=1.6 Hz, 1H), 7.83 (m, 1H), 7.56 (m, 1H), 7.39 (dd, J1=J2=8.0 Hz, 1H), 4.80 (s, 2H), 4.30 (q, J=6.8 Hz, 2H), 3.86 (t, J=6.0 Hz, 2H), 3.15 (t, J=5.6 Hz, 2H), 1.32 (t, J=6.8 Hz, 3H); LCMS [M+H]: 366.

Workup

  1. customwas removed under reduced pressure
  2. customto give a dark brown solid
  3. customThe product was used in the next step without any further purification
  4. additionStep (ii): To the dark brown solid was added dichloromethane (30 mL) and Hunig's Base (5 mL)
  5. dissolutionhad dissolved
  6. temperaturecooled in an ice-bath
  7. additionfollowed by the addition of 3-isocyanato-benzoic acid ethyl ester (0.613 g) as a solution in anhydrous dichloromethane (10 mL) in a drop wise fashion
  8. additionwas added
  9. extractionthe reaction mixture was then extracted with CH2Cl2 (60 mL)
  10. extractionThe organic extract
  11. washwas washed with brine (2×20 mL)
  12. customdried
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto give desired crude product
  16. customThe crude product was then purified

Sources & evidence

ORD record
ord-51fc6f4dcda6448ca4269ed61e5a15f3
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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