Sodium Bicarbonate → 7-(4-Cyanophenyl)-5-methyl-2-(propan-2-yl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile

HRID 1046830Notes

Reaction equation

[CH:1]([C:4]1[N:8]=[C:7]([NH2:9])[NH:6][N:5]=1)([CH3:3])[CH3:2].[C:10]([C:12]([C:22](=O)[CH3:23])=[CH:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1)#[N:11].C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:18]([C:17]1[CH:20]=[CH:21][C:14]([CH:13]2[N:6]3[N:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[N:8]=[C:7]3[NH:9][C:22]([CH3:23])=[C:12]2[C:10]#[N:11])=[CH:15][CH:16]=1)#[N:19]

Participants

Conditions

Temperature: 55 °C

Procedure

Under an atmosphere of argon, 3-isopropyl-1H-1,2,4-triazole-5-amine (241 mg, 1.9 mmol) and 4-(2-cyano-3-oxobut-1-en-1-yl)benzonitrile (300 mg, 1.5 mmol, 0.8 eq.) were dissolved in DMF (3 ml), and solid sodium bicarbonate (803 mg, 9.6 mmol, 5 eq.) was added. The mixture was stirred at 55° C. overnight. The mixture was then filtered and the DMF was distilled off from the filtrate under reduced pressure. The residue was suspended in methanol (2 ml), and the solid was then filtered off and dried under high vacuum (34 mg, 7% of theory). The filtrate was acidified with 1 N hydrochloric acid and purified by preparative HPLC (Kromasil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA), which gave a second product fraction (67 mg, 13% of theory) as a solid.

Workup

filtrationThe mixture was then filtered
distillationthe DMF was distilled off from the filtrate under reduced pressure
filtrationthe solid was then filtered off
customdried under high vacuum (34 mg, 7% of theory)
custompurified by preparative HPLC (Kromasil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA), which
customgave a second product fraction (67 mg, 13% of theory) as a solid

Sources & evidence

ORD record: ord-8be775331dd0458185c33a60e3b7d307
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569314B2

Reaction notes

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