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

HRID 1482984Notes

Reaction equation

HRID 1482984 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:7]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:8][C:9]2[N:13]3[CH2:14][CH2:15][NH:16][C@H:17]([CH:18]([CH3:20])[CH3:19])[C:12]3=[N:11][C:10]=2[CH:21]=1)(=[O:3])[CH3:2].Cl[C:27]1[N:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[C:30]([C:37](=[O:39])[CH3:38])=[CH:29][N:28]=1.CCN(C(C)C)C(C)C.O>CC(O)C.C(Cl)Cl>[C:1]([O:4][CH2:5][C:6]1[C:7]([S:22]([CH3:25])(=[O:23])=[O:24])=[CH:8][C:9]2[N:13]3[CH2:14][CH2:15][N:16]([C:27]4[N:32]=[C:31]([C:33]([F:34])([F:35])[F:36])[C:30]([C:37](=[O:39])[CH3:38])=[CH:29][N:28]=4)[C@H:17]([CH:18]([CH3:19])[CH3:20])[C:12]3=[N:11][C:10]=2[CH:21]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 220974501-(2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanoneHCID 89816096(R)-(1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetate

Product 1

HCID 89815881(R)-(2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetateYield 59.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-(1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetate (160 mg, 0.456 mmol) in iPrOH (4 mL) and DCM (2 mL) was added 1-(2-chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanone (306 mg, 1.37 mmol) and DIEA (353 mg, 2.74 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)-(2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetate (150 mg, 44.4% yield) as a yellow oil.

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-922ca8a2720f4f61ba5f7bc5d9a72107
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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