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

HRID 1847085Notes

Reaction equation

HRID 1847085 reaction equation
C(O)(=O)C.[F:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[F:16])[N:12]([CH2:17][CH2:18][CH:19]=O)[C:11](=[O:21])[CH:10]=[N:9]2.[NH2:22][CH2:23][C@@H:24]1[CH2:28][N:27]([C:29]2[CH:30]=[CH:31][C:32]3[O:33][CH2:34][C:35](=[O:39])[NH:36][C:37]=3[N:38]=2)[C:26](=[O:40])[CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CO>[F:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[F:16])[N:12]([CH2:17][CH2:18][CH2:19][NH:22][CH2:23][C@@H:24]1[CH2:28][N:27]([C:29]3[CH:30]=[CH:31][C:32]4[O:33][CH2:34][C:35](=[O:39])[NH:36][C:37]=4[N:38]=3)[C:26](=[O:40])[CH2:25]1)[C:11](=[O:21])[CH:10]=[N:9]2

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 867249736-[(4R)-4-(Aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneHCID 867250073-(6,7-Difluoro-2-oxoquinoxalin-1(2H)-yl)propanal

Product 1

HCID 867250086-[(4R)-4-({[3-(6,7-Difluoro-2-oxoquinoxalin-1(2H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetic acid (32 mg, 0.58 mmol) was added to a mixture of 3-(6,7-difluoro-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), molecular sieve (4 A, 0.1 g) and methanol (4 ml). The obtained mixture was stirred for 20 minutes, cooled on ice and sodium triacetoxyborohydride (0.11 g, 0.58 mmol) was gradually added thereto. Then, the mixture was stirred at room temperature for 4 hours, an aqueous solution of sodium hydrogen carbonate was added thereto and the mixture was extracted with ethyl acetate. The obtained crude product was purified by silica gel column chromatography (dichloromethane/methanol) to yield 15 mg (7%) of the title compound.

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 silica gel column chromatography (dichloromethane/methanol)

Sources & evidence

ORD record
ord-3f33af627a7846b1871241ec3d4d3922
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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