Malononitrile → HCID 89647451, compound

HRID 531200Notes

Reaction equation

HRID 531200 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[C:10](#[N:14])[CH2:11][C:12]#[N:13].C(N(CC)CC)C.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([C:32]2[CH2:36][C:35](=[O:37])[N:34]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[N:33]=2)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31]>C(O)C>[NH2:13][C:12]1[O:37][C:35]2[N:34]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[N:33]=[C:32]([C:26]3[CH:27]=[CH:28][C:29]([O:30][CH3:31])=[C:24]([O:23][CH3:22])[CH:25]=3)[C:36]=2[CH:6]([C:5]2[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=2)[C:11]=1[C:10]#[N:14]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 8471TriethylamineHCID 680234-FluorobenzaldehydeHCID 89650063HCID 89650063, compound

Product 1

HCID 89647451HCID 89647451, compoundYield 51.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 4-fluorobenzaldehyde (70.0 μL, 0.675 mmol, 1.0 equ.), malononitrile (45.0 mg, 0.675 mmol, 1.0 equ.) and triethylamine (90.0 μL, 0.675 mmol, 1.0 equ.) in ethanol (3.0 mL) was stirred for 1 min, followed by the addition of the 3-(3,4-dimethoxyphenyl)-1-phenyl-1H-pyrazol-5(4H)-one (200 mg, 0.675 mmol, 1 equ.). The reaction mixture was concentrated after 19 h and the crude material was purified by column chromatography (25% ethyl acetate in hexanes to 100% ethyl acetate). The yellow solid was further purified by re-crystallization from ethanol to give 6-amino-3-(3,4-dimethoxyphenyl)-4-(4-fluorophenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (164 mg, 0.350 mmol, 12%) as a white solid. 1H-NMR (400 MHz) CDCl3: 7.80-7.78 (d, 2H), 7.52-7.48 (t, 2H), 7.38-7.35 (t, 1H), 7.25-7.21 (m, 2H), 7.05-6.95 (m, 4H), 6.75-6.73 (d, 1H), 4.91 (s, 1H), 4.84 (s, 1H), 3.84 (s, 3H), 3.71 (s, 3H), 13C-NMR (100 MHz) CDCl3: 163.2, 157.8, 149.2, 148.7, 147.5, 144.9, 138.6, 137.4, 129.3, 129.1, 129.0, 127.1, 125.0, 121.5, 119.8, 119.0, 115.9, 115.7, 110.8, 109.9, 96.6, 64.0, 55.8, 55.7, 37.5; LC/MS-MS: 469.3→403.1 m/z; GS1 and GS2 at 30, DP=6, CE=35, CXP=26, tR=4.16 min.

Workup

  1. concentrationThe reaction mixture was concentrated after 19 h
  2. customthe crude material was purified by column chromatography (25% ethyl acetate in hexanes to 100% ethyl acetate)
  3. customThe yellow solid was further purified by re-crystallization from ethanol

Sources & evidence

ORD record
ord-b97ac4b1b0eb4a25a4a514f7d2a0640a
Source dataset
uspto-grants-2016_05
Patent number
US09353121B2

Reaction notes

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