Acetic Acid → 6-[(4R)-4-{[3-(7-Fluoro-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1847090Notes

Reaction equation

HRID 1847090 reaction equation
C(O)(=O)C.[F:5][C:6]1[CH:15]=[C:14]2[C:9]([N:10]=[CH:11][C:12](=[O:20])[N:13]2[CH2:16][CH2:17][CH:18]=O)=[CH:8][CH:7]=1.[NH2:21][C@H:22]1[CH2:26][N:25]([C:27]2[CH:28]=[CH:29][C:30]3[O:31][CH2:32][C:33](=[O:37])[NH:34][C:35]=3[N:36]=2)[C:24](=[O:38])[CH2:23]1.C(OC(=O)N[C@@H]1CC(=O)NC1)(C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN(C)C=O>[F:5][C:6]1[CH:15]=[C:14]2[C:9]([N:10]=[CH:11][C:12](=[O:20])[N:13]2[CH2:16][CH2:17][CH2:18][NH:21][C@H:22]2[CH2:26][N:25]([C:27]3[CH:28]=[CH:29][C:30]4[O:31][CH2:32][C:33](=[O:37])[NH:34][C:35]=4[N:36]=3)[C:24](=[O:38])[CH2:23]2)=[CH:8][CH:7]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 71301758tert-Butyl [(3R)-5-oxopyrrolidin-3-yl]carbamateHCID 867249916-[(4R)-4-amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneHCID 867250133-(7-Fluoro-2-oxoquinoxalin-1(2H)-yl)propanal

Product 1

HCID 867250146-[(4R)-4-{[3-(7-Fluoro-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Acetic acid (0.042 ml, 0.70 mmol) was added to a mixture of 3-(7-fluoro-2-oxoquinoxalin-1(2H)-yl)propanal (0.120 g, 0.54 mmol), 6-[(4R)-4-amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (synthesized using [(3R)-5-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester synthesized with reference to WO2004/22536 in the same manner as in Reference Examples 20, 21 and 22; 0.185 g, 0.70 mmol) and N,N-dimethylformamide (1.6 ml). The mixture was stirred for 0.5 hours, to which sodium triacetoxyborohydride (0.15 g, 0.70 mmol) was gradually added and stirred for 12 hours. An aqueous solution of sodium hydrogen carbonate was added to the reaction mixture under cooling on ice and the mixture was extracted with ethyl acetate. The obtained crude product was purified by thin layer chromatography (dichloromethane/methanol) to yield 70 mg (29%) of the title compound.

Workup

  1. customsynthesized
  2. customsynthesized with reference to WO2004/22536 in the same manner as in Reference Examples 20, 21 and 22
  3. additionwas gradually added
  4. temperatureunder cooling on ice
  5. extractionthe mixture was extracted with ethyl acetate
  6. customThe obtained crude product
  7. customwas purified by thin layer chromatography (dichloromethane/methanol)

Sources & evidence

ORD record
ord-293ae2fb844341899a990d057b13e099
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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