Hydrochloric Acid → 6-(4-{[2-Hydroxy-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one

HRID 1847005Notes

Reaction equation

HRID 1847005 reaction equation
COC[O:4][CH:5]([CH2:25][N:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][C:27]1=[O:38])[CH2:6][NH:7][CH:8]1[CH2:12][N:11]([C:13]2[CH:14]=[CH:15][C:16]3[O:21][CH2:20][C:19](=[O:22])[NH:18][C:17]=3[CH:23]=2)[C:10](=[O:24])[CH2:9]1.Cl>CO.O1CCCC1>[OH:4][CH:5]([CH2:25][N:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][C:27]1=[O:38])[CH2:6][NH:7][CH:8]1[CH2:12][N:11]([C:13]2[CH:14]=[CH:15][C:16]3[O:21][CH2:20][C:19](=[O:22])[NH:18][C:17]=3[CH:23]=2)[C:10](=[O:24])[CH2:9]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867249356-(4-{[2-(Methoxymethoxy)-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 867249366-(4-{[2-Hydroxy-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-oneYield 61.6%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

6-(4-{[2-(Methoxymethoxy)-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (115 mg, 0.220 mmol) was dissolved in a mixed solvent of methanol/tetrahydrofuran (1:1,2 ml). To this solution was added 4N hydrochloric acid aqueous solution (1 ml) under cooling on ice and the mixture was stirred at 60° C. for 7 hours. The reaction solution was cooled in the air, and the solvent was then removed under reduced pressure. To the residue was added 1N aqueous sodium hydroxide solution under cooling on ice to neutralize the residue which was then extracted using a lower layer solvent of chloroform/methanol/water (7:3:1). The extract was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) to yield 65 mg (61%) of the title compound in the form of a yellowish solid.

Workup

  1. temperatureunder cooling on ice
  2. temperatureThe reaction solution was cooled in the air
  3. customthe solvent was then removed under reduced pressure
  4. additionTo the residue was added 1N aqueous sodium hydroxide solution
  5. temperatureunder cooling on ice
  6. extractionwas then extracted
  7. dry with materialThe extract was dried over anhydrous sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-b7234e47f1834ee7b2f220f8109716a7
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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