Benzaldehyde → 6-Amino-3-(3,4-dimethoxyphenyl)-1-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

HRID 531195Notes

Reaction equation

HRID 531195 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][O:22][C:23]1[CH:24]=[C:25]([C:31]2[CH2:35][C:34](=[O:36])[N:33]([CH3:37])[N:32]=2)[CH:26]=[CH:27][C:28]=1[O:29][CH3:30]>C(O)C>[NH2:12][C:11]1[O:36][C:34]2[N:33]([CH3:37])[N:32]=[C:31]([C:25]3[CH:26]=[CH:27][C:28]([O:29][CH3:30])=[C:23]([O:22][CH3:21])[CH:24]=3)[C:35]=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 896499703-(3,4-dimethoxyphenyl)-1-methyl-1H-pyrazol-5(4H)-one

Product 1

HCID 896469546-Amino-3-(3,4-dimethoxyphenyl)-1-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrileYield 9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of benzaldehyde (145 μL, 1.44 mmol, 1.0 equ.), malononitrile (90.0 mg, 1.44 mmol, 1.0 equ.) and triethylamine (200 μL, 1.44 mmol, 1.0 equ.) in ethanol (5.0 mL) was stirred for 1 min, followed by the addition of 3-(3,4-dimethoxyphenyl)-1-methyl-1H-pyrazol-5(4H)-one (336 mg, 1.44 mmol, 1 equ.). The reaction mixture was concentrated after 24 h. The crude material was purified by column chromatography. (25% ethyl acetate in hexanes to 100% ethyl acetate), then re-crystallized from ethanol and washed with hexanes and ethanol to give 6-amino-3-(3,4-dimethoxyphenyl)-1-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (48.5 mg, 9%, 0.124 mmol) as a yellow solid. 1H-NMR (400 MHz) CDCl3: 7.29-7.28 (d, 2H), 7.23-7.21 (d, 2H), 7.00-6.98 (d, 1H), 6.88 (s, 1H), 6.72-6.70 (d, 2H), 4.84 (s, 1H), 4.75 (s, 2H), 3.82 (s, 6H), 3.60 (s, 3H), 13C-NMR (100 MHz) CDCl3: 157.6, 148.7, 148.6, 146.1, 145.7, 143.1, 128.9, 127.5, 127.4, 125.6, 119.3, 119.3, 110.9, 109.7, 94.7, 64.4, 55.7, 55.6, 38.3, 34.1; LC/MS-MS: 389.1→323.0 m/z; GS1 and GS2 at 30, DP=66, CE=31, CXP=22, tR=3.82 min.

Workup

  1. concentrationThe reaction mixture was concentrated after 24 h
  2. customThe crude material was purified by column chromatography
  3. custom(25% ethyl acetate in hexanes to 100% ethyl acetate), then re-crystallized from ethanol
  4. washwashed with hexanes and ethanol

Sources & evidence

ORD record
ord-9dff265c722e4036937bee064f5738aa
Source dataset
uspto-grants-2016_05
Patent number
US09353121B2

Reaction notes

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