2,4-Difluorobenzoic acid hydrazide → 7-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(2,4-difluorophenyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HRID 1889070Notes

Reaction equation

HRID 1889070 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][C:18](OCC)=[N:17][CH2:16][CH2:15]1)=[O:13].[F:23][C:24]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:25]=1[C:26]([NH:28][NH2:29])=O>C(O)CCC>[Cl:1][C:2]1[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:15][CH2:16][N:17]2[C:26]([C:25]3[CH:30]=[CH:31][C:32]([F:34])=[CH:33][C:24]=3[F:23])=[N:28][N:29]=[C:18]2[CH2:19]1)=[O:13]

Participants

4

Reactant 2

HCID 27369222,4-Difluorobenzoic acid hydrazideHCID 665993991-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-5-(ethyloxy)-1,2,3,6-tetrahydropyrazine

Product 1

HCID 714598627-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(2,4-difluorophenyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 1-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5-(ethyloxy)-1,2,3,6-tetrahydropyrazine (0.167 g, 0.5 mmol, e.g. see preparation below) and 2,4-difluorobenzohydrazide (0.086 g, 0.500 mmol, CAS [118737-62-5], commercially available e.g. from Matrix Scientific or ABCR) in 1-butanol (1 ml) was heated at reflux for 1 hour. After cooling to room temperature the solvent was evaporated and the residue was purified by mass-directed automated (preparative) HPLC (MDAP). The residue was triturated with diethyl ether/isohexane and the solid was collected and dried to give 7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(2,4-difluorophenyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (0.032 g) as a white solid. The solid was dried at 50° C. under high vacuum for 1 day.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hour
  3. customwas evaporated
  4. customthe residue was purified
  5. customThe residue was triturated with diethyl ether/isohexane
  6. customthe solid was collected
  7. customdried

Sources & evidence

ORD record
ord-d6a5ed9c23ed494685f52d2e5690e1a4
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

Loading…