O-Phenylenediamine → 8-Amino-N-(2-aminophenyl)-3-cyclobutylimidazo[1,5-a]pyrazine-1-carboxamide

HRID 2402716Notes

Reaction equation

[C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].C[Al](C)C.[NH2:13][C:14]1[C:15]2[N:16]([C:20]([CH:27]3[CH2:30][CH2:29][CH2:28]3)=[N:21][C:22]=2[C:23](OC)=[O:24])[CH:17]=[CH:18][N:19]=1>C1(C)C=CC=CC=1>[NH2:13][C:14]1[C:15]2[N:16]([C:20]([CH:27]3[CH2:28][CH2:29][CH2:30]3)=[N:21][C:22]=2[C:23]([NH:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[NH2:8])=[O:24])[CH:17]=[CH:18][N:19]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A suspension of 1,2-phenylenediamine (60 mg, 0.6 mmol) in toluene (2.0 mL) was treated with a 2M solution of trimethylaluminum in toluene (0.5 mL) effecting the formation of a pink solution. After 5 min this solution was treated with solid methyl 8-amino-3-cyclobutylimidazo[1,5-a]pyrazine-1-carboxylate (30 mg, 0.1 mmol) and the mixture heated at 120° C. for 30 min then stirred at rt overnight. The mixture was then partitioned between 2M NaOH (10 mL) & EtOAc (10 mL) and stirred for 15 min. The organic layer was separated and the aqueous layer extracted further with EtOAc (3×10 mL). The combined organics were washed with brine, dried and concentrated in vacuo to give ˜85% pure 8-amino-N-(2-aminophenyl)-3-cyclobutylimidazo[1,5-a]pyrazine-1-carboxamide which was used without purification.

Workup

customThe mixture was then partitioned between 2M NaOH (10 mL) & EtOAc (10 mL)
stirringstirred for 15 min
customThe organic layer was separated
extractionthe aqueous layer extracted further with EtOAc (3×10 mL)
washThe combined organics were washed with brine
customdried
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-5c98034353124c1f95900f04ae679059
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796455B2

Reaction notes

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