Malononitrile → 4-amino-6,7,8,9-tetrahydro-2-(1H-indazol-5-yl)-2H-quinolizine-1,3-dicarbonitrile

HRID 218489Notes

Reaction equation

HRID 218489 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]=O)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[C:12](#[N:16])[CH2:13][C:14]#[N:15].N1CCCCC1.[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C:24]1=[CH:29][C:30]#[N:31]>CCO>[NH2:15][C:14]1[N:23]2[C:24]([CH2:25][CH2:26][CH2:27][CH2:28]2)=[C:29]([C:30]#[N:31])[CH:10]([C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[NH:1][N:2]=[CH:3]3)[C:13]=1[C:12]#[N:16]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 8082PiperidineHCID 212506441H-Indazole-5-carboxaldehydeHCID 667255472-Piperidinylidene-ethanenitrile

Product 1

HCID 690440194-amino-6,7,8,9-tetrahydro-2-(1H-indazol-5-yl)-2H-quinolizine-1,3-dicarbonitrileYield 42.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a mixture of 1H-indazole-5-carboxaldehyde (200 mg, 1.37 mmol), from Synthetic Preparation 1, and malononitrile (100 mg, 1.51 mmol) in EtOH (5 mL) was added piperidine (0.2 mL). The mixture was stirred at rt for 2 hr, after which the solid (140 mg) was collected by filtration. This solid and 2-piperidinylidene-ethanenitrile (100 mg, 0.82 mmol; per Synthetic Preparation 5) were combined in EtOH (5 mL). The resulting mixture was kept at 90° C. for 1 hr. After cooling to rt, the solvent was removed in vacuo. The residue was purified on flash column (silica gel) and crystallized further in acetate to afford 4-amino-6,7,8,9-tetrahydro-2-(1H-indazol-5-yl)-2H-quinolizine-1,3-dicarbonitrile (110 mg, 25.4%) (Cpd. No. 305). 1H-NMR (400 MHz, CD3OD): δ=8.02 (s, 1H), 7.58 (s, 1H), 7.53 (d, 1H), 7.34 (d, 1H), 4.53 (s, 1H), 3.63 (d, 2H), 2.72 (m, 2H), 1.95 (m, 1H), 1.73-1.88 (m, 3H) ppm.

Workup

  1. filtrationafter which the solid (140 mg) was collected by filtration
  2. waitThe resulting mixture was kept at 90° C. for 1 hr
  3. temperatureAfter cooling to rt
  4. customthe solvent was removed in vacuo
  5. customThe residue was purified on flash column (silica gel)
  6. customcrystallized further in acetate

Sources & evidence

ORD record
ord-2a991c5ebaf942e385711bcb7af885cd
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Reaction notes

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