Malononitrile → 6-Amino-4-(4-methoxyphenyl)-1,3-dimethyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

HRID 531202Notes

Reaction equation

HRID 531202 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]=O)=[CH:7][CH:8]=1.[C:11](#[N:15])[CH2:12][C:13]#[N:14].C(N(CC)CC)C.[CH3:23][N:24]1[C:28](=[O:29])[CH2:27][C:26]([CH3:30])=[N:25]1>C(O)C>[NH2:14][C:13]1[O:29][C:28]2[N:24]([CH3:23])[N:25]=[C:26]([CH3:30])[C:27]=2[CH:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:12]=1[C:11]#[N:15]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 8471TriethylamineHCID 176733H-Pyrazol-3-one, 2,4-dihydro-2,5-dimethyl-HCID 312444-Methoxybenzaldehyde

Product 1

HCID 896497026-Amino-4-(4-methoxyphenyl)-1,3-dimethyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrileYield 44%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of anisaldehyde (350 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 (321 mg, 2.87 mmol, 1 equ.). The reaction mixture was concentrated after 24 h and the crude material was purified by column chromatography (25% ethyl acetate in hexanes to 100% ethyl acetate). The yellow solid was washed with ethanol and hexanes, and re-crystallized from ethanol to give 6-amino-4-(4-methoxyphenyl)-1,3-dimethyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (370 mg, 1.25 mmol, 44%) as a white solid. 1H-NMR (400 MHz) CDCl3: 7.12-7.10 (d, 2H), 6.85-6.83 (d, 2H), 4.61 (s, 2H), 4.55 (s, 1H), 3.79 (s, 3H), 3.69 (s, 3H), 1.80 (s, 3H) 13C-NMR (100 MHz) CDCl3: 158.8, 157.9, 144.5, 144.4, 134.5, 128.8, 119.3, 114.0, 96.4, 64.2, 55.2, 36.7, 33.7, 12.7; LC/MS-MS: 297.0→231.2 m/z; GS1 and GS2 at 30, DP=61, CE=27, CXP=16, tR=3.71 min.

Workup

  1. concentrationThe reaction mixture was concentrated after 24 h
  2. customthe crude material was purified by column chromatography (25% ethyl acetate in hexanes to 100% ethyl acetate)
  3. washThe yellow solid was washed with ethanol and hexanes
  4. customre-crystallized from ethanol

Sources & evidence

ORD record
ord-c556d007dd4a422ebf9a7c67017395f6
Source dataset
uspto-grants-2016_05
Patent number
US09353121B2

Reaction notes

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