Oxalyl chloride → 5-Cyano-furan-2-carboxylic acid [2'fluoro-5-(4-methyl-piperazin-1-yl)-biphenyl-2-yl]-amide
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([N+:14]([O-])=O)=[CH:12][CH:11]=[C:10]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)[CH:9]=1.[C:24]([C:26]1[O:30][C:29]([C:31](O)=[O:32])=[CH:28][CH:27]=1)#[N:25].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>[Pd].CO.ClCCl.CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[C:10]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)[CH:11]=[CH:12][C:13]=1[NH:14][C:31]([C:29]1[O:30][C:26]([C:24]#[N:25])=[CH:27][CH:28]=1)=[O:32]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
The procedure of Example 9, step (c) was followed using 93.2 mg (0.225 mmol based on 76% purity) of 1-(2′-fluoro-6-nitro-biphenyl-3-yl)-4-methyl-piperazine (as prepared in the previous step), 46 mg of 10% palladium on carbon, 37.0 mg (0.270 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 35.3 μL (0.405 mmol) of oxalyl chloride, 5.0 μL of anh DMF, and 94.1 μL (0.540 mmol) of DIEA. Chromatography on a 5-g silica SPE column with 1-4% MeOH-dichloromethane afforded 69.8 mg (77%) of the title compound as a yellow resin. 1H-NMR (CDCl3; 400 MHz): δ 8.04 (d, 1H, J=9.0 Hz), 7.93 (br s, 1H), 7.434-7.48 (m, 1H), 7.37 (td, 1H, J=7.5, 1.8 Hz), 7.22-7.31 (m, 2H), 7.13, 7.18 (AB q, 2H, J=3.7 Hz), 7.02 (dd, 1H, J=9.0, 2.9 Hz), 6.88 (d, 1H, J=2.9 Hz), 3.24-3.27 (m, 4H), 2.57-2.60 (m, 4H), and 2.36 (s, 3H). Mass spectrum (ESI, m/z): Calcd. for C23H21FN4O2, 405.2 (M+H), found 405.2.
Sources & evidence
- ORD record
- ord-7f64e3695bb644dc93d3c422ff68749d
- Source dataset
- uspto-grants-2010_01
- Patent number
- US07645755B2
Reaction notes
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