Water → 7-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-phenyl-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

HRID 1893421Notes

Reaction equation

HRID 1893421 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=3[Cl:23])=O)[CH2:10][C:5]2=[N:4][C:3]=1[C:24]([F:27])([F:26])[F:25].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.COCCOC.[OH2:43]>C(OCC)(=O)C.CCCC(C)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:23][C:14]1[C:15]([C:19]([F:22])([F:21])[F:20])=[CH:16][CH:17]=[CH:18][C:13]=1[C:11]([N:9]1[CH2:8][CH2:7][N:6]2[C:2]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:3]([C:24]([F:27])([F:26])[F:25])[N:4]=[C:5]2[CH2:10]1)=[O:43]

Participants

8

Reactant 4

HCID 962WaterHCID 80711,2-Dimethoxyethane2×HCID 66827Phenylboronic AcidHCID 497852033-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

Product 1

HCID 497852857-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-phenyl-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazineYield 51.3%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 78922-MethylpentaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.100 g, 0.210 mmol, Example 19), phenylboronic acid (0.0384 g, 0.315 mmol), bis(triphenylphosphine)palladium(II)chloride (0.0147 g, 0.021 mmol) and 1,2-dimethoxyethane (DME) (5 mL) were heated at 100° C. for 4 h in a 1,2-dimethoxyethane (DME) (5 mL)/water (5.00 mL) mixture. The reaction mixture was diluted with ethyl acetate (50 ml) and extracted with ethyl acetate (2×50 ml). The combined extracts were washed with brine and dried through a hydromatrix cartridge (Varian, 10 g). The filtrate was concentrated to an oil that was purified by mass-directed automated preparative HPLC to afford, after trituration in iso-hexane, 7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-phenyl-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.051 g, 0.108 mmol, 51.3% yield).

Workup

  1. extractionextracted with ethyl acetate (2×50 ml)
  2. washThe combined extracts were washed with brine
  3. customdried through a hydromatrix cartridge (Varian, 10 g)
  4. concentrationThe filtrate was concentrated to an oil that
  5. customwas purified
  6. customto afford

Sources & evidence

ORD record
ord-5bcbbc87aed24c2faeec9d64f745f212
Source dataset
uspto-grants-2013_08
Patent number
US08513248B2

Reaction notes

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