Nitrogen → 6-Bromopyrrolo[2,1-F][1,2,4]triazin-4-amine

HRID 73687

Reaction equation

HRID 73687 reaction equation
Cl.[NH2:2][N:3]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]1C#N.[C:11](O)(=O)C.[CH:15]([NH2:17])=[NH:16].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N#N>C(O)C>[Br:8][C:6]1[CH:5]=[C:4]2[N:3]([CH:7]=1)[N:2]=[CH:11][N:16]=[C:15]2[NH2:17]

Participants

6

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 160693Formamidine acetateHCID 666412681-Amino-4-bromo-1H-pyrrole-2-carbonitrile hydrochloride

Product 1

HCID 579552016-Bromopyrrolo[2,1-F][1,2,4]triazin-4-amineYield 75.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred suspension of 1-Amino-4-bromo-1H-pyrrole-2-carbonitrile hydrochloride (17 g, 61.1 mmol) in absolute ethanol (350 mL) was added formamidine acetate (31.8 g, 305 mmol) and potassium phosphate (64.9 g, 305 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 solids were taken up in refluxing MeOH and treated with decolorizing carbon, then filtered thru Celite and concentrated dryness in vacuo. The solids were taken up in THF:DCE (1:3) and filtered thru a pad of silica. Removal of the solvent in vacuo provided a yellowish-brown solid. This material was recrystallized from THF:hexanes to provide the desired compound as a yellow solid (9.86 g, 75% yield). (81%). 1H-NMR (DMSO): δ 7.85 (bs, 2H), 7.81 (s, 1H), 7.80 (d, 1H, J=2 Hz), 6.96 (d, 1H, J=2 Hz).

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. temperaturein refluxing MeOH
  7. additiontreated with decolorizing carbon
  8. filtrationfiltered thru Celite
  9. concentrationconcentrated dryness in vacuo
  10. filtrationfiltered
  11. customRemoval of the solvent in vacuo
  12. customprovided a yellowish-brown solid
  13. customThis material was recrystallized from THF

Sources & evidence

ORD record
ord-b855cc33a47c4702bcdf8e99551d67bd
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Linked notes

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