Diisopropylethylamine → 2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)-4-nitrobenzamide
Reaction equation
[F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:16][CH:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O>[F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4]([NH:16][CH:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]1)=[O:6]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 2-fluoro-5-methoxy-4-nitro-benzoic acid (Intermediate 29; 861 mg, 4.00 mmol) in DMA (20 mL) was added 4-amino-1-methylpiperidine (Fluorochem; 503 mg, 4.40 mmol) followed by DIPEA (1.4 mL, 8.00 mmol) and HATU (1.68 g, 4.40 mmol) and the resulting yellow solution stirred at room temperature for 1 hr. The solvent was removed under reduced pressure and the residue taken up in methanol (approx 10 mL) and loaded onto a 20 g SCX-2 cartridge washing with methanol (50 mL) and eluting with 7 N methanolic ammonia (50 mL) to give a yellow solid, 1.47 g. This was purified by flash silica chromatography (Companion, 40 g, 0-5% ammonia in methanol/DCM) to give the desired product as a pale yellow solid (1.25 g, 4.00 mmol, 100%.)
Workup
- customThe solvent was removed under reduced pressure
- washwashing with methanol (50 mL)
- washeluting with 7 N methanolic ammonia (50 mL)
- customto give a yellow solid, 1.47 g
- customThis was purified by flash silica chromatography (Companion, 40 g, 0-5% ammonia in methanol/DCM)
Sources & evidence
- ORD record
- ord-a43d83e3fa8d446abfa3d2546dd0ba1d
- Source dataset
- uspto-grants-2010_05
- Patent number
- US07709471B2
Reaction notes
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