Dimethylformamide → (R)-methyl 2-(4-bromo-3-(trifluoromethyl)phenyl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

HRID 1521538Notes

Reaction equation

HRID 1521538 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].[Br:25][C:26]1[C:27]([C:33]([F:36])([F:35])[F:34])=NC(Cl)=N[CH:31]=1.CCN(C(C)C)[CH:40]([CH3:42])[CH3:41].CN(C=O)C>O.CCOC(C)=O>[Br:25][C:26]1[CH:31]=[CH:42][C:40]([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])=[CH:41][C:27]=1[C:33]([F:36])([F:35])[F:34]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 114254905-Bromo-2-chloro-4-(trifluoromethyl)pyrimidineHCID 89815671(R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

Product 1

HCID 89816123(R)-methyl 2-(4-bromo-3-(trifluoromethyl)phenyl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylateYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of (R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (45 mg, 0.128 mmol), 5-bromo-2-chloro-4-(trifluoromethyl)pyrimidine (40 mg, 1.2 eq.), DIPEA (90 μL, 4 eq.) and DMF (1.5 mL) was put in Microwave Oven and heated 90 min. at 130° C. The mixture was participated between EtOAc and water. The aqueous layer was extracted twice by EtOAc. The combined organic layers were washed by brine, dried over Na2SO4. After filtration and concentration, the residue was purified by ISCO (12 g column, 10-40% EtOAc in Hexanes) to afford 34.4 mg (47% yield) of (R)-methyl 2-(4-bromo-3-(trifluoromethyl)phenyl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate.

Workup

  1. extractionThe aqueous layer was extracted twice by EtOAc
  2. washThe combined organic layers were washed by brine
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by ISCO (12 g column, 10-40% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-15ab3e0945f742e08a0160a1b4ecb4e0
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

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