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

HRID 1893422Notes

Reaction equation

HRID 1893422 reaction equation
Br[C:2]1N2CCN(C(C3C=CC=C(C(F)(F)F)C=3[Cl:23])=O)CC2=NC=1.Cl.Br[C:26]1[N:30]2[CH2:31][CH2:32][N:33]([C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[C:38]=3[Cl:47])=[O:36])[CH2:34][C:29]2=[N:28][CH:27]=1.CB1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.ClCCl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[ClH:23].[Cl:47][C:38]1[C:39]([C:43]([F:46])([F:45])[F:44])=[CH:40][CH:41]=[CH:42][C:37]=1[C:35]([N:33]1[CH2:32][CH2:31][N:30]2[C:26]([CH3:2])=[CH:27][N:28]=[C:29]2[CH2:34]1)=[O:36]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 497852013-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hydrochlorideHCID 497852023-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

Product 1

HCID 497852867-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hydrochlorideYield 26.3%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
110 °C

Procedure

3-bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.204 g, 0.5 mmol, the free base of Example 18) was dissolved in 1,4-dioxane (3 mL), trimethylboroxine (0.084 mL, 0.600 mmol), potassium carbonate (0.104 g, 0.750 mmol) and tetrakis(triphenylphosphine) palladium (0) (0.058 g, 0.050 mmol) were added. The mixture was heated at 110° C. for 16 h. The mixture was poured on to water (100 ml) and extracted in to ethyl acetate (3×50 ml). Combined extracts were washed with water (3×50 ml), brine (50 ml), dried over anhydrous sodium sulfate and concentrated to a dark oil, (0.336 g). The oil was purified by MDAP to afford a glass, which was dissolved in dichloromethane (5 ml) and treated with 4N HCl in dioxane (1 mL). The solvents were removed in vacuo and the resulting solid triturated in diethyl ether to afford 7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hydrochloride (0.050 g, 0.132 mmol, 26.3% yield).

Workup

  1. extractionextracted in to ethyl acetate (3×50 ml)
  2. washCombined extracts were washed with water (3×50 ml), brine (50 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated to a dark oil, (0.336 g)
  5. customThe oil was purified by MDAP
  6. customto afford a glass, which
  7. customThe solvents were removed in vacuo
  8. customthe resulting solid triturated in diethyl ether

Sources & evidence

ORD record
ord-8d1e11f2113f45ba98b645431de6822e
Source dataset
uspto-grants-2013_08
Patent number
US08513248B2

Reaction notes

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