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

HRID 655167노트

반응식

HRID 655167 반응식
[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[CH2:31][CH2:30][C@@H:29]([NH2:32])[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:32][C@H:29]2[CH2:30][CH2:31][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]

참가 물질

5

반응물 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 59486114(1R,3R)-3-(3-pyridyl)cyclopentylamine

생성물 1

HCID 67135152(3S)-8-amino-9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-[(1S,3S)-3-(3-pyridyl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile수율 16.3%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
91 °C

실험 절차

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 (1.00 g, 3.61 mmol), (1R,3R)-3-(3-pyridyl)cyclopentylamine (702 mg, 4.33 mmol) and diisopropylethylamine (1.38 mL, 7.94 mmol) in anhydrous DMSO (18 mL) was stirred at 91° 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-(3-pyridyl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile (247 mg, 16%) as a yellow powder.

후처리

  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)

출처 및 근거

ORD 기록
ord-28752afb544545fba91224d2fa3a7efb
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071591B2

반응 노트

불러오는 중…