methyl 5-formyl-1H-indazole-3-carboxylate → 5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-1H-indazole-3-carboxylic acid methyl ester

HRID 218479

Reaction equation

HRID 218479 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH:14]=O)[CH:12]=2)[NH:7][N:6]=1)=[O:4].N/[C:17](=[CH:20]\[CH3:21])/[C:18]#[N:19]>CC(O)=O.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH:14]3[C:13]([C:5]#[N:6])=[C:8]([CH3:9])[NH:7][C:20]([CH3:21])=[C:17]3[C:18]#[N:19])[CH:12]=2)[NH:7][N:6]=1)=[O:4]

Participants

5

Reactant 2

HCID 24958745methyl 5-formyl-1H-indazole-3-carboxylateHCID 86589747Aminocrotononitrile

Product 1

HCID 249594685-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-1H-indazole-3-carboxylic acid methyl esterYield 177.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-formyl-1H-indazole-3-carboxylic acid methyl ester (92 mg, 0.45 mmol) and aminocrotononitrile (74 mg, 0.9 mmol) in HOAc (1 mL) was kept at 110° C. for 15 mins. After cooling to rt, the reaction mixture was diluted with EtOAc, washed with brine, dried, and concentrated. The crude product was purified by TLC to afford 5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-1H-indazole-3-carboxylic acid methyl ester (133 mg, 89%) (Cpd. No. 85, Table 2). 1H-NMR (400 MHz, DMSO-D6): δ=8.04 (s, 1H), 7.72 (s, 1H), 7.49 (d, 1H), 4.58 (s, 1H), 4.02 (s, 3H), 2.0 (s, 6H) ppm.

Workup

  1. washwashed with brine
  2. customdried
  3. concentrationconcentrated
  4. customThe crude product was purified by TLC

Sources & evidence

ORD record
ord-4a69144bfcc8477da8286e7ef8c507b0
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Linked notes

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