Hydrazine hydrate (1:1) → 4-(3-amino-1H-indazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile

HRID 218477Notes

Reaction equation

HRID 218477 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]2[C:15]([C:16]#[N:17])=[C:14]([CH3:18])[NH:13][C:12]([CH3:19])=[C:11]2[C:20]#[N:21])[CH:6]=[CH:7][C:8]=1F)#[N:2].O.[NH2:23][NH2:24]>C(O)CCC>[NH2:2][C:1]1[C:3]2[C:8](=[CH:7][CH:6]=[C:5]([CH:10]3[C:15]([C:16]#[N:17])=[C:14]([CH3:18])[NH:13][C:12]([CH3:19])=[C:11]3[C:20]#[N:21])[CH:4]=2)[NH:24][N:23]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 597632464-(3-Cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile

Product 1

HCID 249594654-(3-amino-1H-indazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrileYield 57.01%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 4-(3-cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile (9.5 g, 34.14 mmol), from Synthetic Example 1, and hydrazine hydrate (10 g, 312 mmol) in n-butyl alcohol (75 mL) was kept at 80° C. for 5 hr. The mixture was cooled and concentrated. Sodium bicarbonate solution (sat.) was added to the residue, and the mixture was extracted with ethyl acetate. The organic phases were combined, dried, and concentrated to afford 4-(3-amino-1H-indazol-5-yl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile (5.6 g, 57.01%) as a pale yellow solid (Cpd. No. 82, Table 2). 1H-NMR (300 MHZ, DMSO-D6): δ=11.39 (br. s, 1H), 9.47 (br. s, 1H), 7.50 (m, 1H), 7.20 (d, 1H), 7.11 (dd, 1H), 5.34 (br. s, 2H), 4.34 (s, 1H), 2.01 (s, 6H) ppm.

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated
  3. additionSodium bicarbonate solution (sat.) was added to the residue
  4. extractionthe mixture was extracted with ethyl acetate
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e02bb167ecf24f06ba7237fe2a701dd2
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Reaction notes

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