Toluene → 1-(6-Fluoro-3,4-dihydro-5-oxa-1,2a-diazaacenaphthylen-2-yl)ethylamine
Reaction equation
C(OC(=O)[NH:7][CH:8]([C:10]1[N:20]2[C:21]3[C:16]([O:17][CH2:18][CH2:19]2)=[C:15]([F:22])[CH:14]=[CH:13][C:12]=3[N:11]=1)[CH3:9])(C)(C)C.FC1C=CC2=C3C=1OCCN3C(C(NC(=O)C)C)=N2.C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[F:22][C:15]1[CH:14]=[CH:13][C:12]2=[C:21]3[C:16]=1[O:17][CH2:18][CH2:19][N:20]3[C:10]([CH:8]([NH2:7])[CH3:9])=[N:11]2Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To an ice-cooled solution of the mixture of [1-(6-fluoro-3,4-dihydro-5-oxa-1,2a-diaza-acenaphthylen-2-yl)ethyl]carbamic acid tert-butyl ester and N-[1-(6-fluoro-3,4-dihydro-5-oxa-1,2a-diaza-acenaphthylen-2-yl)ethyl]acetamide from the previous step in DCM (15 mL) was added TFA (3 mL) and the mixture was stirred at RT for 2 h. Toluene was added and volatiles were removed under reduced pressure, the resulting residue was dissolved in MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product was eluted with 0.5M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo. Purification by column chromatography (Si—PCC, gradient 2-8% 2M NH3/MeOH in DCM) afforded the title compound as a light brown gum (185.6 mg, 65%, 2 steps). LCMS (Method B): RT 1.54 min [M+H]+ 222
Workup
- customvolatiles were removed under reduced pressure
- dissolutionthe resulting residue was dissolved in MeOH
- washThe cartridge was washed with MeOH
- washthe product was eluted with 0.5M NH3/MeOH
- additionThe product containing fractions
- concentrationconcentrated in vacuo
- customPurification by column chromatography (Si—PCC, gradient 2-8% 2M NH3/MeOH in DCM)
Sources & evidence
- ORD record
- ord-d6f4cd8f18964beeb1e9dcaf850624cf
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08653089B2
Reaction notes
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