Hydrochloric Acid → 1-{5-[4-(2,2-Difluoro-cyclopropylmethyl)-piperazin-1-yl]-pyridin-2-yl}-1,2,3,4-tetrahydroquinoxaline

HRID 40545Notes

Reaction equation

HRID 40545 reaction equation
[F:1][C:2]1([F:31])[CH2:4][CH:3]1[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[CH:14][C:15]([N:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21](C(O)=O)[CH2:20][CH2:19]3)=[N:16][CH:17]=2)[CH2:8][CH2:7]1.Cl>O1CCOCC1>[F:31][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[CH:14][C:15]([N:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:21][CH2:20][CH2:19]3)=[N:16][CH:17]=2)[CH2:8][CH2:7]1

Participants

4

Reactant 2

HCID 313Hydrochloric Acid3×HCID 687373104-{5-[4-(2,2-difluoro-cyclopropylmethyl)-piperazin-1-yl]-pyridin-2-yl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid

Product 1

HCID 669259181-{5-[4-(2,2-Difluoro-cyclopropylmethyl)-piperazin-1-yl]-pyridin-2-yl}-1,2,3,4-tetrahydroquinoxaline

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent4×

Procedure

0.3 g of tert-butyl ester of 4-{5-[4-(2,2-difluoro-cyclopropylmethyl)-piperazin-1-yl]-pyridin-2-yl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid is put in 5 mL of dioxane, to which 2.32 ml of 4N HCl in dioxane is added. The reaction mixture is stirred at room temperature in a closed environment for 18 h. Once again, 2.32 mL of 4N HCl in dioxane is added, and the reaction mixture is stirred for a further 18 h at room temperature. 2.32 ml of 4N HCl in dioxane is added once again, and the reaction mixture is stirred for a further 18 h at room temperature. After concentration to dryness, the reaction mixture is diluted with a solution of 50 ml of 1N HCl in water and extracted with 100 ml of diethyl ether. The organic phase is washed again with 50 ml of 1N HCl in water. The aqueous phases are then combined, basified with K2CO3 in powder form to pH 10, and extracted 3 times with 50 ml of dichloromethane. The resultant organic phases are combined, washed with a saturated aqueous solution of sodium chloride, dried over MgSO4 and concentrated to dryness. 0.24 g of 1-{5-[4-(2,2-difluoro-cyclopropylmethyl)-piperazin-1-yl]-pyridin-2-yl}-1,2,3,4-tetrahydroquinoxaline is obtained.

Workup

  1. additionis added
  2. stirringthe reaction mixture is stirred for a further 18 h at room temperature
  3. stirringthe reaction mixture is stirred for a further 18 h at room temperature
  4. concentrationAfter concentration to dryness
  5. additionthe reaction mixture is diluted with a solution of 50 ml of 1N HCl in water
  6. extractionextracted with 100 ml of diethyl ether
  7. washThe organic phase is washed again with 50 ml of 1N HCl in water
  8. extractionextracted 3 times with 50 ml of dichloromethane
  9. washwashed with a saturated aqueous solution of sodium chloride
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-8628cf64972c427585a0e26e2f59ec9b
Source dataset
uspto-grants-2013_09
Patent number
US08530473B2

Reaction notes

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