Nitrogen → Pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 1099248Notes

Reaction equation

HRID 1099248 reaction equation
Cl.N[N:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]#[N:9].C(O)(=O)C.[CH:14]([NH2:16])=[NH:15].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N#N>C(O)C>[N:15]1[N:3]2[CH:7]=[CH:6][CH:5]=[C:4]2[C:8]([NH2:9])=[N:16][CH:14]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 160693Formamidine acetateHCID 509909371-Amino-1H-pyrrole-2-carbonitrile hydrochloride

Product 1

HCID 10441749Pyrrolo[2,1-f][1,2,4]triazin-4-amineYield 44.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred suspension of 1-Amino-1H-pyrrole-2-carbonitrile hydrochloride (50 g, 0.35 mol) in absolute ethanol (800 mL) was added formamidine acetate (181.3 g, 1.74 mol) and potassium phosphate (370 g, 1.74 mol). The suspension was heated for 18 hours@78° C. (under N2), then cooled, filtered and concentrated to dryness in vacuo. The residue was mixed with ice water (2 L) and the dark grayish-brown solids were collected by suction filtration. The filter cake was washed with water, sucked dry and the solids were dissolved (on the funnel) with hot ethyl acetate and filtered into a collection vessel. The dark solution was filtered through a long plug of 30/40 Magnesol and the pale yellow filtrate was concentrated to dryness in vacuo to afford a yellow-tinged solid (20.6 g, 44.1% yield). The plug was washed with ethyl acetate/ethanol and the washings were concentrated in vacuo to afford additional material, 10.7 g (23%). Extraction of the aqueous work-up filtrate with ethyl acetate followed by drying, Magnesol filtration and concentration gave another 6.3 g (14%) of clean product, bringing the total recovery to 37.6 g (81%). 1H-NMR (CD3OD): δ 7.72 (s, 1H), 7.52 (dd, 1H, J=2.5, 1.6 Hz), 6.85 (dd, 1H, J=4.5, 1.6 Hz), 6.64 (dd, 1H, J=4.5, 2.7 Hz) LC/MS (+esi): m/z=135.1 [M+H].

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. concentrationconcentrated to dryness in vacuo
  4. additionThe residue was mixed with ice water (2 L)
  5. filtrationthe dark grayish-brown solids were collected by suction filtration
  6. washThe filter cake was washed with water
  7. customsucked dry
  8. dissolutionthe solids were dissolved (on the funnel) with hot ethyl acetate
  9. filtrationfiltered into a collection vessel
  10. filtrationThe dark solution was filtered through a long plug of 30/40 Magnesol
  11. concentrationthe pale yellow filtrate was concentrated to dryness in vacuo

Sources & evidence

ORD record
ord-3913cd354ca74573a1a5a1793fdefb3a
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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