Cesium carbonate → (6S)-7-(2-Chloro-4-fluorobenzyl)-6-methyl-3-pyrazin-2-yl-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one

HRID 576730Notes

Reaction equation

HRID 576730 reaction equation
[CH3:1][C@H:2]1[CH2:7][N:6]2[C:8]([C:11]3[CH:16]=[N:15][CH:14]=[CH:13][N:12]=3)=[N:9][N:10]=[C:5]2[C:4](=[O:17])[NH:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:24][C:25]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:26]=1[CH2:27]Br>CN(C=O)C.O>[Cl:24][C:25]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:26]=1[CH2:27][N:3]1[C@@H:2]([CH3:1])[CH2:7][N:6]2[C:8]([C:11]3[CH:16]=[N:15][CH:14]=[CH:13][N:12]=3)=[N:9][N:10]=[C:5]2[C:4]1=[O:17]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27250621-(Bromomethyl)-2-chloro-4-fluorobenzeneHCID 86279012(S)-6-methyl-3-(pyrazin-2-yl)-6,7-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one

Product 1

HCID 86279013(6S)-7-(2-Chloro-4-fluorobenzyl)-6-methyl-3-pyrazin-2-yl-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-oneYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of Example 77 (40 mg, 0.17 mmol) in DMF (1.7 mL) was added cesium carbonate (226 mg, 0.70 mmol) and 2-chloro-4-fluorobenzyl bromide (58 mg, 0.26 mmol) and the reaction mixture was stirred for 18 hours. The reaction mixture was diluted with water and extracted with EtOAc. The organic layers were combined, washed with brine, dried with Na2SO4, filtered, concentrated and purified by flash column chromatography (0-20% iPrOH in EtOAc) to provide the desired compound (41 mg, 65%). MS (ESI): mass calcd. for C17H14ClFN6O, 372.8; m/z found, 373.1 [M+H]+. 1H NMR (400 MHz, DMSO) δ 9.47 (d, J=1.3 Hz, 1H), 8.84-8.80 (m, 2H), 7.61-7.55 (m, 1H), 7.55-7.50 (m, 1H), 7.26-7.19 (m, 1H), 5.10 (d, J=15.9 Hz, 1H), 5.01-4.89 (m, 1H), 4.70 (dd, J=13.9, 4.6 Hz, 1H), 4.48 (d, J=16.0 Hz, 1H), 4.13-4.03 (m, 1H), 1.18 (d, J=6.7 Hz, 3H).

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash column chromatography (0-20% iPrOH in EtOAc)

Sources & evidence

ORD record
ord-893317c0915748b69f2cdc0e219e19d9
Source dataset
uspto-grants-2015_05
Patent number
US09040534B2

Reaction notes

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