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

HRID 531183Notes

Reaction equation

HRID 531183 reaction equation
[NH2:1][C:2]1[O:21][C:6]2[N:7]([CH3:20])[N:8]=[C:9]([C:10]3[CH:15]=[CH:14][C:13](OC)=[C:12](OC)[CH:11]=3)[C:5]=2[CH:4]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:3]=1[C:29]#[N:30].F[C:32]1[CH:39]=[CH:38]C(C=O)=[CH:34][CH:33]=1.C(#N)CC#N.C(N(CC)CC)C.COC1C=C(C2CC(=O)N(C)N=2)C=CC=1OC>C(O)C>[NH2:1][C:2]1[O:21][C:6]2[N:7]([C:20]3[CH:38]=[CH:39][CH:32]=[CH:33][CH:34]=3)[N:8]=[C:9]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:5]=2[CH:4]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[C:3]=1[C:29]#[N:30]

Participants

7

Reactant 5

HCID 8010MalononitrileHCID 8471TriethylamineHCID 680234-FluorobenzaldehydeHCID 896475236-Amino-3-(3,4-dimethoxyphenyl)-4-(4-fluorophenyl)-1-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrileHCID 896499703-(3,4-dimethoxyphenyl)-1-methyl-1H-pyrazol-5(4H)-one

Product 1

HCID 896500416-Amino-4-(4-fluorophenyl)-1,3-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrileYield 67%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6-amino-3-(3,4-dimethoxyphenyl)-4-(4-fluorophenyl)-1-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile UC-E21: A mixture of 4-fluorobenzaldehyde (300 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 3-(3,4-dimethoxyphenyl)-1-methyl-1H-pyrazol-5(4H)-one (672 mg, 2.87 mmol, 1 equ.). The precipitate formed was filtered out and washed with ethanol and hexanes, and re-crystallized from ethanol to give 6-amino-4-(4-fluorophenyl)-1,3-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (782 mg, 1.93 mmol, 67%) as a white powder. 1H-NMR (400 MHz) DMSO: 7.20-7.18 (m, 2H), 7.09-7.03 (m, 5H), 6.96-6.95 (d, 1H), 6.80-6.78 (d, 2H), 5.02 (s, 1H), 3.77 (s, 3H), 3.69 (s, 3H), 3.62 (s, 3H) 13C-NMR (100 MHz) DMSO: 162.6, 159.0, 148.7, 146.0, 144.6, 141.0, 141.0, 129.8, 129.7, 125.9, 120.4, 119.0, 115.7, 115.4, 111.8, 109.8, 94.7, 55.8, 55.7, 37.3, 34.4; LC/MS-MS: 407.1→341.1 m/z; GS1 and GS2 at 30, DP=71, CE=33, CXP=22, tR=3.86 min.

Workup

  1. customThe precipitate formed
  2. filtrationwas filtered out
  3. washwashed with ethanol and hexanes
  4. customre-crystallized from ethanol

Sources & evidence

ORD record
ord-c6aa42ab616b401980b97f1cab0bf826
Source dataset
uspto-grants-2016_05
Patent number
US09353121B2

Reaction notes

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