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

HRID 655152Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 655152
[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([C@H:26]2[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27]2)[CH:25]=[CH:24][CH:23]=[N: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:31][C@H:28]2[CH2:29][CH2:30][C@H:26]([N:21]3[CH:25]=[CH:24][CH:23]=[N:22]3)[CH2:27]2)[C:3]=1[F:20]

Komponenten

5

Edukt 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 67135041trans-3-(1H-pyrazol-1-yl)cyclopentylamine

Produkt 1

HCID 67134964(3S)-8-amino-9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-[trans-3-(1H-pyrazol-1-yl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrileAusbeute 15 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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 (580 mg, 2.09 mmol), trans-3-(1H-pyrazol-1-yl)cyclopentylamine (380 mg, 2.51 mmol) and di-isopropylethylamine (0.80 mL, 4.59 mmol) in anhydrous DMSO (12 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-[trans-3-(1H-pyrazol-1-yl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile (125 mg, 15%) as a yellow powder.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-90e9c49157c949e39812d956ae993211
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071591B2

Notizen zur Reaktion

Wird geladen…