Diisopropylethylamine → tert-Butyl [(3S)-1-(3-nitro-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yl)piperidin-3-yl]carbamate
Reaction equation
I[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][N:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][NH:7]2.[NH:15]1[CH2:20][CH2:19][CH2:18][C@H:17]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:16]1.CCN(C(C)C)C(C)C>C(O)CCC>[N+:12]([C:11]1[CH:10]=[N:9][C:8]2[NH:7][CH2:6][CH2:5][CH2:4][C:3]=2[C:2]=1[N:15]1[CH2:20][CH2:19][CH2:18][C@H:17]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[CH2:16]1)([O-:14])=[O:13]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 140 °C
Procedure
A mixture of 5-iodo-6-nitro-1,2,3,4-tetrahydro-1,8-naphthyridine (0.50 g, 1.6 mmol), tert-butyl (3S)-piperidin-3-ylcarbamate (0.39 g, 2.0 mmol), DIPEA (0.64 g, 5.0 mmol) and 1-butanol (6 mL) was heated at 140° C. for 14 h, then allowed to cool. The solvent was removed under reduced pressure, then the residue was diluted with EtOAc and washed with aq. Na2CO3 solution. The organic layer was washed with water and brine, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using CombiFlash® apparatus, eluting with 10 to 90% EtOAc in hexanes, to give the sub-title compound (0.55 g, 89%). LCMS calc. for C18H28N5O4 (M+H)+: m/z=378.2. Found: 378.1.
Workup
- temperatureto cool
- customThe solvent was removed under reduced pressure
- additionthe residue was diluted with EtOAc
- washwashed with aq. Na2CO3 solution
- washThe organic layer was washed with water and brine
- customdried
- concentrationconcentrated under reduced pressure
- customThe residue was purified by column chromatography on silica gel using CombiFlash® apparatus
- washeluting with 10 to 90% EtOAc in hexanes
Sources & evidence
- ORD record
- ord-7719aeeddc7e40c680c279a77c2b4317
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09200004B2
Reaction notes
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