Diisopropylethylamine → 1-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione

HRID 870317Notes

Reaction equation

[OH:1][C:2](=[C:13]1[C:18](=[O:19])OC(C)(C)OC1=O)[CH2:3][C:4]1[CH:9]=[C:8]([F:10])[C:7]([F:11])=[CH:6][C:5]=1[F:12].Cl.[F:24][C:25]([F:36])([F:35])[C:26]1[N:30]2[CH2:31][CH2:32][NH:33][CH2:34][C:29]2=[N:28][N:27]=1.C(N(C(C)C)CC)(C)C>C(OC(C)C)(=O)C>[O:19]=[C:18]([N:33]1[CH2:32][CH2:31][N:30]2[C:26]([C:25]([F:36])([F:24])[F:35])=[N:27][N:28]=[C:29]2[CH2:34]1)[CH2:13][C:2](=[O:1])[CH2:3][C:4]1[CH:9]=[C:8]([F:10])[C:7]([F:11])=[CH:6][C:5]=1[F:12]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 5-(1-hydroxy-2-(2,4,5-trifluorophenyl)-ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (10 g), 3-trifluoromethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine hydrochloride (7.2 g), diisopropyl ethylamine (4.5 g), and isopropyl acetate (100 mL) are heated to about 85° C. and stirred for about 4 hours. The reaction mass is then cooled to about 30° C. and quenched with water (90 mL). The organic layer is separated, washed with 5% sodium chloride solution (3×50 mL) and distilled off completely under vacuum to afford 12 g of the title compound. (Yield: 93.3%; purity by HPLC: 95.7%)

Workup

temperatureThe reaction mass is then cooled to about 30° C.
customquenched with water (90 mL)
customThe organic layer is separated
washwashed with 5% sodium chloride solution (3×50 mL)
distillationdistilled off completely under vacuum

Sources & evidence

ORD record: ord-0d73c8df403f4e16a61b7e2e70bc24e8
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969558B2

Reaction notes

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