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

HRID 1847026ノート

反応式

HRID 1847026 の反応式
[F:1][CH:2]([CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[N:9]=[CH:8][C:7]1=[O:18])[CH:3]=O.[NH2:19][CH:20]1[CH2:24][N:23]([C:25]2[CH:26]=[CH:27][C:28]3[O:33][CH2:32][C:31](=[O:34])[NH:30][C:29]=3[CH:35]=2)[C:22](=[O:36])[CH2:21]1.C(O)(=O)C.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN(C)C=O>[F:1][CH:2]([CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[N:9]=[CH:8][C:7]1=[O:18])[CH2:3][NH:19][CH:20]1[CH2:24][N:23]([C:25]2[CH:26]=[CH:27][C:28]3[O:33][CH2:32][C:31](=[O:34])[NH:30][C:29]=3[CH:35]=2)[C:22](=[O:36])[CH2:21]1

参加物

8

反応物 5

HCID 176Acetic AcidHCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 824984066-(4-Amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-oneHCID 902618892-Fluoro-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propanal

生成物 1

HCID 867249546-(4-{[2-Fluoro-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one収率 18%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

A crude product of 2-Fluoro-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propanal (196 mg) and 6-(4-amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (Reference Example 6; 147 mg, 0.595 mmol) were dissolved in a mixed solution of dichloromethane (20 ml) and N,N-dimethylformamide (2 ml). Acetic acid (0.068 ml, 1.190 mmol) and anhydrous sodium sulfate (300 mg) were added to the solution at room temperature and the mixture was stirred for 14 hours. Sodium triacetoxyborohydride (252 mg, 1.190 mmol) was added to the reaction solution, the mixture was stirred for 4 hours and then the solvent was removed under reduced pressure. A lower layer solvent of chloroform/methanol/water (7:3:1) was added to the residue and the resultant was 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 silica gel column chromatography (chloroform/methanol) and preparative thin layer chromatography (silica gel, chloroform/methanol=20:1) to yield 50 mg (18%) of the title compound in the form of a white solid.

後処理

  1. stirringthe mixture was stirred for 4 hours
  2. customthe solvent was removed under reduced pressure
  3. additionA lower layer solvent of chloroform/methanol/water (7:3:1) was added to the residue
  4. additionby adding saturated sodium bicarbonate water
  5. temperatureunder cooling on ice
  6. extractionThe mixture was extracted with a lower layer solvent of chloroform/methanol/water (7:3:1)
  7. dry with materialthe extract was dried over anhydrous sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (chloroform/methanol) and preparative thin layer chromatography (silica gel, chloroform/methanol=20:1)

出典と根拠

ORDレコード
ord-80c4d4f7c91c48b29fdb73c2876e2dfe
出典データセット
uspto-grants-2015_02
特許番号
US08952010B2

反応ノート

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