Acetyl chloride → 1-{4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl}ethan-1-one

HRID 1099261Notes

Reaction equation

[N:1]1[N:2]2[CH:10]=[CH:9][CH:8]=[C:3]2[C:4]([NH2:7])=[N:5][CH:6]=1.[Al+3].[Cl-].[Cl-].[Cl-].[C:15](Cl)(=[O:17])[CH3:16].C(=O)(O)[O-].[Na+]>[N+](C1C=CC=CC=1)([O-])=O>[NH2:7][C:4]1[C:3]2=[CH:8][CH:9]=[C:10]([C:15](=[O:17])[CH3:16])[N:2]2[N:1]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of pyrrolo[2,1-f][1,2,4]triazin-4-amine (1.00 g, 7.46 mmol) in nitrobenzene (40 mL) was added AlCl3 (2.98 g, 22.36 mmol), followed by acetyl chloride (2.34 g, 29.82 mmol). The resulting solution was heated (60° C.) for 5 h and cooled to rt. The reaction mixture was poured onto ice-water and solid sodium bicarbonate was added with stirring until the solution was basic. This mixture was extracted with ethyl acetate (3×100 mL) and then the combined organic layers were concentrated under reduced pressure. The residue was stirred with MeOH (100 mL) and potassium carbonate (5 g) overnight. The solid was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by HPLC using a gradient of 5-30% MeCN in water to afforded 448.0 mg (34%) of the title compound. 1H-NNR (DMSO-d6) δ 9.63 (bs, 1H), 8.47 (bs, 1H), 8.03 (s, 1H), 7.76 (d, J=3.2 Hz, 1H), 7.40 (d, J=2.9 Hz, 1H), 2.57 (s, 3H); MS [M+H]+=177.1; LCMS RT=1.37 min.

Workup

temperaturecooled to rt
additionwas added
extractionThis mixture was extracted with ethyl acetate (3×100 mL)
concentrationthe combined organic layers were concentrated under reduced pressure
stirringThe residue was stirred with MeOH (100 mL) and potassium carbonate (5 g) overnight
customThe solid was removed by filtration
concentrationthe filtrate was concentrated under reduced pressure
customThe residue was purified by HPLC

Sources & evidence

ORD record: ord-1f00d029fcdb46c99f2521a2151f1cd1
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143393B2

Reaction notes

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