Hydrochloric Acid → 1-(2-(6-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)-7-oxo-2,6-diazabicyclo(3.2.1)oct-2-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one

HRID 2193386Notes

Reaction equation

HRID 2193386 reaction equation
CO.[O:3]1[C:12]2[CH:11]=[C:10]([CH2:13][NH:14][CH:15]3[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][N:23]4[C:32]5[C:27](=[CH:28][CH:29]=[C:30]([O:33][CH3:34])[CH:31]=5)[N:26]=[CH:25][C:24]4=[O:35])[CH:17]([C:36]([O:38]C)=O)[CH2:16]3)[N:9]=[CH:8][C:7]=2[O:6][CH2:5][CH2:4]1.[OH-].[Na+].Cl>C(OCC)C.CCCCCC.C(OCC)(=O)C.O>[O:3]1[C:12]2[CH:11]=[C:10]([CH2:13][N:14]3[C:36](=[O:38])[CH:17]4[CH2:16][CH:15]3[CH2:20][CH2:19][N:18]4[CH2:21][CH2:22][N:23]3[C:32]4[C:27](=[CH:28][CH:29]=[C:30]([O:33][CH3:34])[CH:31]=4)[N:26]=[CH:25][C:24]3=[O:35])[N:9]=[CH:8][C:7]=2[O:6][CH2:5][CH2:4]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium Hydroxide2×HCID 59398301HCID 59398301, compound

Product 1

HCID 675395261-(2-(6-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)-7-oxo-2,6-diazabicyclo(3.2.1)oct-2-yl)ethyl)-7-methoxyquinoxalin-2(1H)-oneYield 16%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 5 mL of a methanol solution containing 60 mg of methyl 4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)-1-(2-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)ethyl)piperidine-2-carboxylate, 0.2 mL of 20% aqueous sodium hydroxide solution was added at room temperature, and stirred for 1 hour and 10 min. Further, 0.5 mL of 20% aqueous sodium hydroxide solution was added at room temperature, and stirred at the sane temperature for 1 hour and 50 min. The reaction mixture was adjusted to pH 6.2 with 2 mol/L hydrochloric acid under water-cooling, the solvent was removed under reduced pressure, water, ethyl acetate and diethyl ether were added, and the resulting solid (A′) was filtered. Also, the solvent of the filtrate (B′) was removed under reduced pressure. To the residue thus obtained, water, ethyl acetate and diethyl ether were added, the organic layer was separated, and the solvent was removed under reduced pressure. To the residue thus obtained, hexane and diethyl ether were added, and the resulting solid (B) was filtered to give 9 mg of 1-(2-(6-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)-7-oxo-2,6-diazabicyclo(3.2.1)oct-2-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one as a pale yellow solid.

Workup

  1. additionwas added at room temperature
  2. stirringstirred at the sane temperature for 1 hour and 50 min
  3. temperaturecooling
  4. customthe solvent was removed under reduced pressure, water, ethyl acetate and diethyl ether
  5. additionwere added
  6. filtrationthe resulting solid (A′) was filtered
  7. customAlso, the solvent of the filtrate (B′) was removed under reduced pressure
  8. customTo the residue thus obtained
  9. customthe organic layer was separated
  10. customthe solvent was removed under reduced pressure
  11. customTo the residue thus obtained
  12. filtrationthe resulting solid (B) was filtered

Sources & evidence

ORD record
ord-ec37b7c6fa2f404b9a62e7f3bf88821c
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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