Ammonia → 3-Amino-1-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one

HRID 445963Notes

Reaction equation

[BH4-].[Na+].FC(F)(F)C(O)=O.[O:10]=[C:11]([N:25]1[CH2:30][CH2:29][N:28]2[C:31]([C:34]([F:37])([F:36])[F:35])=[N:32][N:33]=[C:27]2[CH2:26]1)[CH:12]=[C:13]([NH2:24])[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23].N>O.C1COCC1>[O:10]=[C:11]([N:25]1[CH2:30][CH2:29][N:28]2[C:31]([C:34]([F:37])([F:36])[F:35])=[N:32][N:33]=[C:27]2[CH2:26]1)[CH2:12][CH:13]([NH2:24])[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23]

Participants

Conditions

Temperature: -6.5 °C

Procedure

In a 250 mL round bottom flask THF (75 mL) was taken. It was cooled to −8 to −5° C. and NaBH4 (1.87 g) was added. After that trifluoroacetic acid (11.3 g) was added dropwise at −15 to −5° C. over a period of 30-45 min. Separately, 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine (5.0 g) was added in small portions into the reaction mixture, keeping the temperature between −10 to −5° C. It was stirred for 1 h at −10 to −0° C. Reaction mixture was poured into cold water. It was basified by adding aq. ammonia solution. Product was extracted in ethyl acetate. The organic layer was collected. It was washed with water and dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-4.9 g; % Y-97.6%; % Purity by HPLC-81.6%).

Workup

custombetween −10 to −5° C
customReaction mixture
extractionProduct was extracted in ethyl acetate
customThe organic layer was collected
washIt was washed with water
dry with materialdried over anhydrous sodium sulfate
customSolvent was evaporated at reduced pressure
customto obtain the product

Sources & evidence

ORD record: ord-165b9e3b0d764053b2887ee56b103b83
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08476437B2

Reaction notes

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