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

HRID 531196Notes

Reaction equation

HRID 531196 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]([CH3:29])=[N:24]1>C(O)C>[NH2:13][C:12]1[O:28][C:27]2[N:23]([CH3:22])[N:24]=[C:25]([CH3:29])[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 176733H-Pyrazol-3-one, 2,4-dihydro-2,5-dimethyl-HCID 680234-Fluorobenzaldehyde

Product 1

HCID 566905026-Amino-4-(4-fluorophenyl)-1,3-dimethyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrileYield 41%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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 mL, 2.87 mmol, 1.0 equ.) in ethanol (8.0 mL) was stirred for 1 min, followed by the addition of 1,3-dimethyl-1H-pyrazol-5(4H)-one (322 mg, 2.87 mmol, 1 equ.). The reaction mixture was concentrated after 24 h and washed with ethanol and hexanes, and re-crystallized from ethanol to give 6-amino-4-(4-fluorophenyl)-1,3-dimethyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (335 mg, 41%, 1.17 mmol) as a white solid. 1H-NMR (400 MHz) DMSO: 7.23-7.20 (m, 2H), 7.16-7.12 (m, 2H), 7.07 (s, 2H), 4.61 (s, 1H), 3.60 (s, 3H), 1.67 (s, 3H), 13C-NMR (100 MHz) DMSO: 162.7, 159.9, 144.6, 142.9, 140.7, 129.9, 120.6, 115.6, 115.4, 96.3, 59.6, 56.4, 36.7, 33.8, 12.8; LC/MS-MS: 285.1→219.1 m/z; GS1 and GS2 at 30, DP=61, CE=27, CXP=14, tR=3.80 min.

Workup

  1. concentrationThe reaction mixture was concentrated after 24 h
  2. washwashed with ethanol and hexanes
  3. customre-crystallized from ethanol

Sources & evidence

ORD record
ord-9e747c21f82d414388c6ef82d813ea6e
Source dataset
uspto-grants-2016_05
Patent number
US09353121B2

Reaction notes

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