Hydrochloric Acid → 6-[(4R)-4-({[2-Hydroxy-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1847055Notes

Reaction equation

HRID 1847055 reaction equation
COC[O:4][CH:5]([CH2:26][N:27]1[C:32](=[O:33])[CH:31]=[N:30][C:29]2[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[N:37][C:28]1=2)[CH2:6][NH:7][CH2:8][C@@H:9]1[CH2:13][N:12]([C:14]2[CH:15]=[CH:16][C:17]3[O:18][CH2:19][C:20](=[O:24])[NH:21][C:22]=3[N:23]=2)[C:11](=[O:25])[CH2:10]1.Cl>CO.O1CCCC1>[OH:4][CH:5]([CH2:26][N:27]1[C:32](=[O:33])[CH:31]=[N:30][C:29]2[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[N:37][C:28]1=2)[CH2:6][NH:7][CH2:8][C@@H:9]1[CH2:13][N:12]([C:14]2[CH:15]=[CH:16][C:17]3[O:18][CH2:19][C:20](=[O:24])[NH:21][C:22]=3[N:23]=2)[C:11](=[O:25])[CH2:10]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867249806-[(4R)-4-({[2-(Methoxymethoxy)-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

Product 1

HCID 601617806-[(4R)-4-({[2-Hydroxy-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 18.3%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

In a mixed solution (2 ml) of methanol/tetrahydrofuran (1:1) was dissolved 6-[(4R)-4-({[2-(Methoxymethoxy)-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (41.3 mg, 0.077 mmol). To this solution was added a 4N hydrochloric acid aqueous solution (1 ml) under cooling on ice and the mixture was stirred at 60° C. for 4 hours. The reaction solution was cooled in the air, and the solvent was then removed under reduced pressure. The residue was dissolved in a lower layer solvent of the chloroform/methanol/water (7:3:1) and alkalized by adding saturated sodium bicarbonate water under cooling on ice. The mixture was extracted with 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 preparative layer chromatography (chloroform/methanol) to yield 7 mg (18%) of the title compound in the form of an orangish 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. dissolutionThe residue was dissolved in a lower layer solvent of the chloroform/methanol/water (7:3:1)
  5. additionby adding saturated sodium bicarbonate water
  6. temperatureunder cooling on ice
  7. extractionThe mixture was extracted with a lower layer solvent of chloroform/methanol/water (7:3:1)
  8. dry with materialthe extract was dried over anhydrous sodium sulfate
  9. customthe solvent was removed under reduced pressure
  10. customThe residue was purified by preparative layer chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-b4fb959e905a45b893121a7a776cf351
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

Loading…