Water → (R)-methyl 2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

HRID 1482989Notes

Reaction equation

HRID 1482989 reaction equation
[CH:1]([C@H:4]1[NH:9][CH2:8][CH2:7][N:6]2[C:10]3[CH:16]=[C:15]([S:17]([CH3:20])(=[O:19])=[O:18])[C:14]([C:21]([O:23][CH3:24])=[O:22])=[CH:13][C:11]=3[N:12]=[C:5]12)([CH3:3])[CH3:2].Cl[C:26]1[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([C:36](=[O:38])[CH3:37])=[CH:28][N:27]=1.CCN(C(C)C)C(C)C.O>CC(O)C.C(Cl)Cl>[C:36]([C:29]1[C:30]([C:32]([F:34])([F:35])[F:33])=[N:31][C:26]([N:9]2[CH2:8][CH2:7][N:6]3[C:10]4[CH:16]=[C:15]([S:17]([CH3:20])(=[O:19])=[O:18])[C:14]([C:21]([O:23][CH3:24])=[O:22])=[CH:13][C:11]=4[N:12]=[C:5]3[C@H:4]2[CH:1]([CH3:3])[CH3:2])=[N:27][CH:28]=1)(=[O:38])[CH3:37]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 220974501-(2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanoneHCID 89815671(R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

Product 1

HCID 89815953(R)-methyl 2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylateYield 44.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (220 mg, 0.627 mmol) in iPrOH (4 mL) and DCM (2 mL) was added 1-(2-chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanone (421 mg, 1.88 mmol) and DIEA (485 mg, 3.76 mmol). The mixture was stirred at 60° C. overnight. Water (5 mL) was added to the mixture and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were washed with water (2×10 mL) and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative TLC to afford (R)-methyl 2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (150 mg, 44.4% yield) as a yellow solid.

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (2×10 mL)
  2. washThe combined organic layers were washed with water (2×10 mL) and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-62be5601954a4ad2b06c4d8197548ac2
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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