Pyrazine-2-Carboxylic Acid Hydrazide → (S)-tert-butyl 6-methyl-3-(pyrazin-2-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate

HRID 576727Notes

Reaction equation

HRID 576727 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][C:5](=S)[CH2:4][N:3]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[N:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[C:22]([NH:24][NH2:25])=O>C(O)CCC>[CH3:1][C@H:2]1[CH2:7][N:6]2[C:22]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][N:16]=3)=[N:24][N:25]=[C:5]2[CH2:4][N:3]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10]

Participants

4

Reactant 2

HCID 258796Pyrazine-2-Carboxylic Acid HydrazideHCID 90402252HCID 90402252, compound

Product 1

HCID 90402323(S)-tert-butyl 6-methyl-3-(pyrazin-2-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylateYield 43.5%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of (S)-tert-butyl 2-methyl-5-thioxopiperazine-1-carboxylate (2.5 g, 10.9 mmol) in n-butanol (10 mL) was added pyrazine-2-carbohydrazide (1.6 g, 11.9 mmol) and the reaction mixture was heated to 120° C. for 12 hours. The reaction mixture as cooled to room temperature, concentrated onto silica gel and purified by flash column chromatography (0-20% MeOH in EtOAc) to provide the desired compound (1.5 g, 43%). 1H NMR (400 MHz, DMSO) δ 9.36 (d, J=1.4 Hz, 1H), 8.78-8.74 (m, 2H), 5.02 (d, J=17.4 Hz, 1H), 4.72 (d, J=12.6 Hz, 2H), 4.53 (d, J=17.4 Hz, 1H), 4.36-4.28 (m, 1H), 1.48 (s, 9H), 1.10 (d, J=6.9 Hz, 3H).

Workup

  1. temperatureThe reaction mixture as cooled to room temperature
  2. concentrationconcentrated onto silica gel
  3. custompurified by flash column chromatography (0-20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-37789c9bfe8e4c61bf47a28ec130ae18
Source dataset
uspto-grants-2015_05
Patent number
US09040534B2

Reaction notes

Loading…