rac-(1R,2S)-N1,N2-dimethylcyclohexane-1,2-diamine → tert-butyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 1468920Notes

Reaction equation

HRID 1468920 reaction equation
[CH:1]([CH:4]1[C:9](=O)[NH:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])([CH3:3])[CH3:2].Br[C:19]1[CH:25]=[C:24]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:23]=[CH:22][C:20]=1[NH2:21].CN[C@@H]1CCCC[C@@H]1NC>CN1C(=O)CCC1.O>[CH:1]([CH:4]1[N:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:7][N:8]2[C:19]3[CH:25]=[C:24]([S:26]([CH3:29])(=[O:27])=[O:28])[CH:23]=[CH:22][C:20]=3[N:21]=[C:9]12)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 7020757rac-(1R,2S)-N1,N2-dimethylcyclohexane-1,2-diamineHCID 201344022-Bromo-4-methanesulfonylanilineHCID 67492477HCID 67492477, compound

Product 1

HCID 89815614tert-butyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylateYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of tert-butyl 2-isopropyl-3-oxopiperazine-1-carboxylate (200 mg, 0.83 mmol) in NMP (3 mL) were added 2-bromo-4-(methylsulfonyl)aniline (207 mg, 0.83 mmol), (1R,2S)—N1,N2-dimethylcyclohexane-1,2-diamine (12.0 mg, 0.08 mmol), K3PO4.3H2O (660 mg, 2.48 mmol) and Cul (16 mg, 0.08 mmol). The mixture was stirred at 150° C. for 1 h in a microwave oven. 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 purified by preparative TLC with CH2Cl2/MeOH 35/1 to afford tert-butyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylate (110 mg, 34% yield) as a white solid. LC-MS m/z 394.1 [M+H]+. 1H NMR (CDCl3 400 MHz): δ 7.94 (s, 1H), 7.83-7.76 (m, 2H), 5.35-5.17 (m, 1H), 4.73-4.42 (m, 1H), 4.22-4.12 (m, 1H), 4.11-3.99 (m, 1H), 3.53-3.37 (m, 1H), 3.03 (s, 3H), 2.38-2.27 (m, 1H), 1.42 (s, 9H), 1.19 (d, J=6.8 Hz, 3H), 0.97 (d, J=6.8 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 TLC with CH2Cl2/MeOH 35/1

Sources & evidence

ORD record
ord-436d1f7009d04cde8a92b5bdf4c972f1
Source dataset
uspto-grants-2015_04
Patent number
US09006245B2

Reaction notes

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