Diisopropylethylamine → 1-(2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)ethanone

HRID 1521508Notes

Reaction equation

HRID 1521508 reaction equation
[CH:1]([CH: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])[CH:14]=[CH:13][C:11]=3[N:12]=[C:5]12)([CH3:3])[CH3:2].Cl[C:22]1[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[C:25]([C:32](=[O:34])[CH3:33])=[CH:24][N:23]=1.CCN(C(C)C)C(C)C>CS(C)=O.O>[CH:1]([CH:4]1[N:9]([C:22]2[N:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[C:25]([C:32](=[O:34])[CH3:33])=[CH:24][N:23]=2)[CH2:8][CH2:7][N:6]2[C:10]3[CH:16]=[C:15]([S:17]([CH3:20])(=[O:18])=[O:19])[CH:14]=[CH:13][C:11]=3[N:12]=[C:5]12)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 220974501-(2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanoneHCID 898159691-Isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine

Product 1

HCID 717359861-(2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)ethanoneYield 20%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine (7.50 mg, 0.03 mmol) in DMSO (1 mL) were added 1-(2-chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanone (11.5 mg, 0.05 mmol) and DIEA (9.90 mg, 0.08 mmol) under N2. The mixture was stirred at 100° C. for 2 h. The mixture was diluted with water (10 mL) and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered, concentrated and then purified by preparative HPLC to afford a racemic mixture of 1-(2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)ethanone (2.40 mg, 20% yield) as a white solid. LC-MS m/z 482.1 [M+H]+. 1H NMR (CD3OD 400 MHz): δ 8.76 (s, 1H), 8.02 (s, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.84-7.83 (m, 1H), 6.15 (d, J=8.0 Hz, 1H), 5.45 (d, J=13.6 Hz, 1H), 4.42-4.36 (m, 1H), 4.20 (brs, 1H), 3.91-3.80 (m, 1H), 3.09 (s, 3H), 2.60-2.46 (m, 4H), 1.34 (d, J=6.8 Hz, 3H), 1.09 (d, J=6.0 Hz, 3H).

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. washThe combined organic layers were washed with brine (10 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by preparative HPLC
  7. customto afford

Sources & evidence

ORD record
ord-ba0853e1be50478a8f931d87197bd64a
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

Loading…