Hydrochloric Acid → 3,4-Diamino-6-(4-methoxy-3-trifluoromethyl-phenyl)-pyridine-2-carbonitrile

HRID 2246438Notes

Reaction equation

HRID 2246438 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=2)[N:5]=[C:4]([C:20]#[N:21])[C:3]=1[N+:22]([O-])=O.Cl.O>CO.[Fe]>[NH2:22][C:3]1[C:4]([C:20]#[N:21])=[N:5][C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([C:16]([F:19])([F:17])[F:18])[CH:9]=2)=[CH:7][C:2]=1[NH2:1]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 589381164-Amino-6-(4-methoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrile

Product 1

HCID 589381133,4-Diamino-6-(4-methoxy-3-trifluoromethyl-phenyl)-pyridine-2-carbonitrileYield 49.5%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 887MethanolSolvent

Procedure

4-Amino-6-(4-methoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrile (65 mg, 0.19 mmol) was suspended in methanol (1.5 ml) and concentrated HCl (0.5 ml) was added dropwise (exotherm). The suspension was stirred while iron powder (37 mg, 0.67 mmol) was added in portions (exotherm), and the mixture was heated to reflux for 1 hour. Mixture was poured into water (20 ml) and extracted with ethyl acetate (20 ml). Organics were dried and evaporated then flash chromatographed over silica (4 g Combiflash cartridge, 7:3 heptane/ethyl acetate) to afford 29 mg of 3,4-diamino-6-(4-methoxy-3-trifluoromethyl-phenyl)-pyridine-2-carbonitrile as a light brown solid. 1H NMR (DMSO) δ 8.08-8.01 (m, 2H) 7.05-7.00 (m, 2H), 3.94 (s, 3H). MS m/z 309.7 (M+1).

Workup

  1. additionwas added in portions (exotherm)
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1 hour
  4. extractionextracted with ethyl acetate (20 ml)
  5. customOrganics were dried
  6. customevaporated
  7. customflash chromatographed over silica (4 g Combiflash cartridge, 7:3 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-e7bc34cb8edb493d9aecafc3a4654ab0
Source dataset
uspto-grants-2010_03
Patent number
US07687515B2

Reaction notes

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