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

HRID 655176ノート

反応式

HRID 655176 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]=[C:23]([C@@H:27]2[CH2:32][CH2:31][CH2:30][C@H:29]([NH2:33])[CH2:28]2)[CH:22]=1.C(N(C(C)C)CC)(C)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:33][C@H:29]2[CH2:30][CH2:31][CH2:32][C@@H:27]([C:23]3[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=3)[CH2:28]2)[C:3]=1[F:20]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 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 67134050cis-3-(3-Pyridyl)cyclohexylamine

生成物 1

HCID 67134794(3S)-8-amino-9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-[cis-3-(3-pyridyl)cyclohexylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile収率 13.4%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
93 °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 (457 mg, 1.65 mmol), cis-3-(3-pyridyl)cyclohexylamine (348 mg, 1.97 mmol) and diisopropylethylamine (0.63 mL, 3.63 mmol) in anhydrous DMSO (8 mL) was stirred at 93° C. for 9 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-[cis-3-(3-pyridyl)cyclohexylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile (96.0 mg, 13%) 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-e3632e92fcb847128d58acf29f7b56af
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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