Sodium Bicarbonate → 1,4-dihydro-4-(1H-indazol-5-yl)-2,6-dimethyl-3,5-pyridinedicarbonitrile

HRID 218481

Reaction equation

HRID 218481 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.[NH2:12]/[C:13](/[CH3:17])=[CH:14]\[C:15]#[N:16].C([O-])(O)=O.[Na+]>CC(O)=O>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]3[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[NH:12][C:7]([CH3:6])=[C:8]3[C:9]#[N:1])=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 5325263(2Z)-3-Amino-2-butenenitrileHCID 212506441H-Indazole-5-carboxaldehyde

Product 1

HCID 249591041,4-dihydro-4-(1H-indazol-5-yl)-2,6-dimethyl-3,5-pyridinedicarbonitrileYield 44%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 1H-indazole-5-carboxaldehyde from Synthetic Preparation 1 (447 mg, 3.1 mmol) and 3-aminocrotononitrile (526.4 mg, 6.41 mmol) in HOAc (10 mL) was kept at 110° C. for 1.5 hr, after which it was cooled to rt. The reaction was treated with NaHCO3 (sat.) to pH 10, and extracted with EtOAc. The organic phases were combined, washed with brine, and dried. Concentration followed by purification with flash chromatography afforded 1,4-dihydro-4-(1H-indazol-5-yl)-2,6-dimethyl-3,5-pyridinedicarbonitrile (370 mg, 44%) (Cpd. No. 80, Table 2). 1H-NMR (400 MHz, CDCl3): δ=8.07 (s, 1H), 7.64 (s, 1H), 7.53 (d, 1H), 7.35 (d, 1H), 4.48 (s, 1H), 2.03 (s, 6H) ppm.

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. customdried
  4. concentrationConcentration
  5. customfollowed by purification with flash chromatography

Sources & evidence

ORD record
ord-279b7ddbe4b742d7b415f99edaec384d
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Linked notes

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