Pyrazine-2-Carboxylic Acid Hydrazide → (6S)-7-[2-Chloro-3-(trifluoromethyl)benzyl]-6-ethyl-3-pyrazin-2-yl-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one

HRID 576724Notes

Reaction equation

HRID 576724 reaction equation
[Cl:1][C:2]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][N:5]1[C@@H:10]([CH2:11][CH3:12])[CH2:9][NH:8][C:7](=S)[C:6]1=[O:14].[N:23]1[CH:28]=[CH:27][N:26]=[CH:25][C:24]=1[C:29]([NH:31][NH2:32])=O>C(O)CCC>[Cl:1][C:2]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][N:5]1[C@@H:10]([CH2:11][CH3:12])[CH2:9][N:8]2[C:29]([C:24]3[CH:25]=[N:26][CH:27]=[CH:28][N:23]=3)=[N:31][N:32]=[C:7]2[C:6]1=[O:14]

Participants

4

Reactant 2

HCID 258796Pyrazine-2-Carboxylic Acid HydrazideHCID 90402575(6S)-1-(2-chloro-3-(trifluoromethyl)benzyl)-6-ethyl-3-thioxopiperazin-2-one

Product 1

HCID 86278949(6S)-7-[2-Chloro-3-(trifluoromethyl)benzyl]-6-ethyl-3-pyrazin-2-yl-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-oneYield 75%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of Intermediate 6 (100 mg, 0.29 mmol) and pyrazine-2-carbohydrazide (39 mg, 0.29 mmol) in 1-butanol (3 mL) was heated to 130° C. for 16 h. After cooling to rt, the reaction was concentrated to give a brown oil. Purification by chromatography (SiO2; hexanes—100% EtOAc) afforded the desired product as a white solid (94 mg, 75%). MS (ESI): mass calcd. for C19H16ClF3N6O, 436.1; m/z found, 437.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 9.62 (d, J=1.5 Hz, 1H), 8.69 (d, J=2.5 Hz, 1H), 8.62 (dd, J=2.5, 1.6 Hz, 1H), 7.77 (d, J=7.7 Hz, 1H), 7.69 (dd, J=7.8, 1.1 Hz, 1H), 7.42 (t, J=7.8 Hz, 1H), 5.56-5.42 (m, 2H), 4.54 (d, J=15.5 Hz, 1H), 4.46 (dd, J=14.1, 4.4 Hz, 1H), 3.77 (ddd, J=9.4, 4.6, 3.5 Hz, 1H), 1.87-1.78 (m, 1H), 1.63-1.53 (m, 1H), 0.97 (t, J=7.4 Hz, 3H).

Workup

  1. concentrationthe reaction was concentrated
  2. customto give a brown oil
  3. customPurification by chromatography (SiO2; hexanes—100% EtOAc)

Sources & evidence

ORD record
ord-145fa5aefd9e421a9406b1942e1a20b2
Source dataset
uspto-grants-2015_05
Patent number
US09040534B2

Reaction notes

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