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

HRID 1847087Notes

Reaction equation

HRID 1847087 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][CH2:13][CH:14]=O)[C:7](=[O:16])[CH:6]=[N:5]2.[NH2:17][CH2:18][C@@H:19]1[CH2:23][N:22]([C:24]2[CH:25]=[CH:26][C:27]3[O:28][CH2:29][C:30](=[O:34])[NH:31][C:32]=3[N:33]=2)[C:21](=[O:35])[CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][CH2:13][CH2:14][NH:17][CH2:18][C@@H:19]1[CH2:23][N:22]([C:24]3[CH:25]=[CH:26][C:27]4[O:28][CH2:29][C:30](=[O:34])[NH:31][C:32]=4[N:33]=3)[C:21](=[O:35])[CH2:20]1)[C:7](=[O:16])[CH:6]=[N:5]2

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 867249736-[(4R)-4-(Aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneHCID 867250113-(6-fluoro-2-oxoquinoxalin-1(2H)-yl)propanal

Product 1

HCID 867250106-[(4R)-4-({[3-(6-Fluoro-2-oxoquinoxalin-1(2H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(6-fluoro-2-oxoquinoxalin-1(2H)-yl)propanal (0.1 g, 0.45 mmol), 6-[(4R)-4-(aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Reference Examples 54, 0.11 g, 0.45 mmol) DMF (3 ml) and molecular sieve (4 A, 0.1 g) was stirred at room temperature for 20 minutes. The reaction mixture was cooled on ice and sodium triacetoxyborohydride (0.12 g, 0.54 mmol) was gradually added thereto. Then, the mixture was stirred at room temperature for 4 hours, a sodium hydrogen carbonate aqueous solution was added thereto and the mixture was extracted with ethyl acetate. The obtained crude product was purified by thin layer chromatography (dichloromethane/methanol) to yield the title compound. 8 mg (2%).

Workup

  1. additionwas gradually added
  2. stirringThen, the mixture was stirred at room temperature for 4 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. customThe obtained crude product
  5. customwas purified by thin layer chromatography (dichloromethane/methanol)

Sources & evidence

ORD record
ord-f2ba8547e75844bb92f6d29d7a0d555b
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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