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

HRID 531197Notes

Reaction equation

HRID 531197 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][N:23]1[C:27](=[O:28])[CH2:26][C:25]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[N:24]1>C(O)C>[NH2:13][C:12]1[O:28][C:27]2[N:23]([CH3:22])[N:24]=[C:25]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:26]=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 1425623H-Pyrazol-3-one, 2,4-dihydro-2-methyl-5-phenyl-

Product 1

HCID 896464776-Amino-4-(4-fluorophenyl)-1-methyl-3-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrileYield 18.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of the 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 1-methyl-3-phenyl-1H-pyrazol-5(4H)-one (500 mg, 2.87 mmol, 1 equ.). The reaction mixture was concentrated after 20 h in vacuo and washed with ethanol and hexanes, and re-crystallized from ethanol to give 6-amino-4-(4-fluorophenyl)-1-methyl-3-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (182 mg, 0.525 mmol, 18%) as a light yellow solid. 1H-NMR (400 MHz) DMSO: 7.50-7.48 (d, 2H), 7.22-7.18 (m, 5H), 7.11 (s, 2H), 7.05-6.98 (t, 2H) 5.04 (s, 1H), 3.78 (s, 3H), 13C-NMR (100 MHz) DMSO: 162.5, 159.1, 146.0, 144.6, 140.9, 133.1, 129.8, 128.5, 127.9, 126.5, 120.4, 115.5, 115.3, 95.5, 59.7, 37.4, 34.5; LC/MS-MS: 347.1→281.0 m/z; GS1 and GS2 at 30, DP=66, CE=31, CXP=14, tR=4.00 min.

Workup

  1. concentrationThe reaction mixture was concentrated after 20 h in vacuo
  2. washwashed with ethanol and hexanes
  3. customre-crystallized from ethanol

Sources & evidence

ORD record
ord-6209eaa486b9414e82cc7e9590e59e1c
Source dataset
uspto-grants-2016_05
Patent number
US09353121B2

Reaction notes

Loading…