Acetic Acid → 6-[(4R)-4-({[3-(3-Methoxy-6-oxopyrido[2,3-b]pyrazin-5 (6H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1847098노트

반응식

HRID 1847098 반응식
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[N:9]([CH2:14][CH2:15][CH:16]=O)[C:10](=[O:13])[CH:11]=[CH:12][C:6]2=[N:5][CH:4]=1.[NH2:18][CH2:19][C@@H:20]1[CH2:24][N:23]([C:25]2[CH:26]=[CH:27][C:28]3[O:29][CH2:30][C:31](=[O:35])[NH:32][C:33]=3[N:34]=2)[C:22](=[O:36])[CH2:21]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[N:9]([CH2:14][CH2:15][CH2:16][NH:18][CH2:19][C@@H:20]3[CH2:24][N:23]([C:25]4[CH:26]=[CH:27][C:28]5[O:29][CH2:30][C:31](=[O:35])[NH:32][C:33]=5[N:34]=4)[C:22](=[O:36])[CH2:21]3)[C:10](=[O:13])[CH:11]=[CH:12][C:6]2=[N:5][CH:4]=1

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2회HCID 867249463-(3-Methoxy-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl)propanalHCID 867249736-[(4R)-4-(Aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

생성물 1

HCID 601620516-[(4R)-4-({[3-(3-Methoxy-6-oxopyrido[2,3-b]pyrazin-5 (6H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one수율 11%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 3-(3-methoxy-6-oxopyrido[2,3-b]pyrazin-5 (6H)-yl)propanal (Reference Example 24, 120 mg, 0.515 mmol) in N,N-dimethylformamide (1.6 ml) were added 6-[(4R)-4-(aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Reference Example 54, 175 mg, 0.66 mmol) and acetic acid (0.04 ml, 0.66 mmol), and the mixture was stirred at room temperature for 30 minutes. The reaction solution was cooled on ice, sodium triacetoxyborohydride (141 mg, 0.66 mmol) was added thereto and stirred overnight at room temperature. Two equivalents of sodium triacetoxyborohydride (282 mg, 1.32 mmol) were further added thereto and the reaction solution was stirred for 2 days. A sodium hydrogen carbonate aqueous solution was added to the reaction solution, which was then extracted with ethyl acetate and the obtained organic layer was washed with water and saturated sodium chloride solution. Subsequently, the organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The obtained crude product was purified by thin layer chromatography (dichloromethane/methanol) to yield 27 mg (11%) of the title compound.

후처리

  1. additionwas added
  2. stirringstirred overnight at room temperature
  3. stirringthe reaction solution was stirred for 2 days
  4. extractionwas then extracted with ethyl acetate
  5. washthe obtained organic layer was washed with water and saturated sodium chloride solution
  6. dry with materialSubsequently, the organic layer was dried over anhydrous sodium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customThe obtained crude product
  9. customwas purified by thin layer chromatography (dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-c7116a3843b0400d90d910421443f6be
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952010B2

반응 노트

불러오는 중…