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

HRID 655147Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 80 °C

Procedure

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 (180 mg, 0.649 mmol), cis-3-(2-pyridyl)cyclopentylamine (158 mg, 0.973 mmol) and triethylamine (0.200 mL, 0.976 mmol) in anhydrous DMSO (3 mL) was stirred at 80° C. for 8 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 (Hexane/EtOAc=1/3) to yield (3S)-8-amino-9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-[cis-3-(2-pyridyl)cyclopentylamino]-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile (diastereomer mixture, 55.6 mg, 20%) as a yellow powder.

Workup

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

Sources & evidence

ORD record: ord-2c4d927b8a1540fd8382f8505d26a2ed
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071591B2

Reaction notes

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