Triethylamine → (3S)-8-amino-9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-[(1S,3S)-3-(2-pyridyl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile

HRID 655141ノート

反応式

HRID 655141 の反応式
[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]([C:17]#[N:18])=[CH:12][N:7]3[C@@H:8]([CH3:11])[CH2:9][O:10][C:5]([C:6]=23)=[C:4](F)[C:3]=1[F:20].[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C@H:27]1[CH2:31][CH2:30][C@H:29]([NH2:32])[CH2:28]1.C(N(CC)CC)C>CS(C)=O>[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]([C:17]#[N:18])=[CH:12][N:7]3[C@@H:8]([CH3:11])[CH2:9][O:10][C:5]([C:6]=23)=[C:4]([NH:32][C@H:29]2[CH2:30][CH2:31][C@H:27]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=3)[CH2:28]2)[C:3]=1[F:20]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 58346338(3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrileHCID 59486146trans-3-(2-Pyridyl)cyclopentylamine

生成物 1

HCID 46910836(3S)-8-amino-9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-[(1S,3S)-3-(2-pyridyl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile収率 19%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
100 °C

実験手順

A mixture of (3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile (1.30 g, 4.69 mmol), (1S,3S)-3-(2-pyridyl)cyclopentylamine (913 mg, 5.63 mmol) and triethylamine (1.30 mL, 9.33 mmol) in anhydrous DMSO (8 mL) was stirred at 100° C. for 7 h. After cooling, the reaction mixture was poured into ice-water and then extracted with CH2Cl2-MeOH. The organic layer was washed with water and brine, and dried over anhyd Na2SO4 followed by the removal of solvent. The crude product was purified by column chromatography (EtOAc) to yield (3S)-8-amino-9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-[(1S,3S)-3-(2-pyridyl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile (364 mg, 19%) as a yellow powder.

後処理

  1. temperatureAfter cooling
  2. extractionextracted with CH2Cl2-MeOH
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhyd Na2SO4
  5. customfollowed by the removal of solvent
  6. customThe crude product was purified by column chromatography (EtOAc)

出典と根拠

ORDレコード
ord-ae7f6aa8539f48318fa3ec99cd807d90
出典データセット
uspto-grants-2011_12
特許番号
US08071591B2

反応ノート

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