Benzaldehyde → 6-Amino-1,3-dimethyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitril

HRID 531190Notes

Reaction equation

HRID 531190 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9](#[N:13])[CH2:10][C:11]#[N:12].C(N(CC)CC)C.[CH3:21][N:22]1[C:26](=[O:27])[CH2:25][C:24]([CH3:28])=[N:23]1>C(O)C>[NH2:12][C:11]1[O:27][C:26]2[N:22]([CH3:21])[N:23]=[C:24]([CH3:28])[C:25]=2[CH:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:10]=1[C:9]#[N:13]

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 8010MalononitrileHCID 8471TriethylamineHCID 176733H-Pyrazol-3-one, 2,4-dihydro-2,5-dimethyl-

Product 1

HCID 896494446-Amino-1,3-dimethyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrilYield 34.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of benzaldehyde (290 μL, 2.87 mmol, 1.0 equ.), malononitrile (190 mg, 2.87 mmol, 1.0 equ.) and triethylamine (400 μL, 2.87 mmol, 1.0 equ.) in ethanol (10 mL) was stirred for 1 min, followed by the addition of 1,3-dimethyl-1H-pyrazol-5(4H)-one (322 mg, 2.87 mmol, 1 equiv.). The reaction mixture was concentrated after 19 h and washed with ethanol and hexanes. The crude material was purified by column chromatography on SiO2 (25% ethyl acetate in n-hexanes to 100% ethyl acetate) and then re-crystallized from ethanol to give 6-amino-1,3-dimethyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitril (263 mg, 0.988 mmol, 34%) as a yellow powder. 1H-NMR (400 MHz) DMSO: 7.34-7.32 (m, 2H), 7.25-7.23 (t, 1H), 7.19-7.17 (d, 2H), 7.05 (s, 2H), 4.57 (s, 1H), 3.60 (s, 3H), 1.66 (s, 3H), 13C-NMR (100 MHz) DMSO: 159.9, 144.6, 144.4, 142.9, 128.8, 128.0, 127.3, 120.6, 96.5, 58.7, 37.5, 33.8, 12.8; LC/MS-MS: 267.0→201.3 m/z; GS1 and GS2 at 30, DP=61, CE=29, CXP=12, tR=3.74 min.

Workup

  1. concentrationThe reaction mixture was concentrated after 19 h
  2. washwashed with ethanol and hexanes
  3. customThe crude material was purified by column chromatography on SiO2 (25% ethyl acetate in n-hexanes to 100% ethyl acetate)
  4. customre-crystallized from ethanol

Sources & evidence

ORD record
ord-6f9974318cfd4245a96f6aec9cba11d9
Source dataset
uspto-grants-2016_05
Patent number
US09353121B2

Reaction notes

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