5-cyanofuran-2-carboxylic Acid → 5-cyano-N-(6-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)pyridin-3-yl)furan-2-carboxamide
Reaction equation
[C:1]([C:3]1[O:7][C:6]([C:8]([OH:10])=O)=[CH:5][CH:4]=1)#[N:2].[CH3:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[C:23]([NH2:24])=[CH:22][CH:21]=[C:20]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)[N:19]=2)[CH2:14][CH2:13]1>>[CH3:11][CH:12]1[CH2:13][CH2:14][N:15]([C:18]2[C:23]([NH:24][C:8]([C:6]3[O:7][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)=[O:10])=[CH:22][CH:21]=[C:20]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)[N:19]=2)[CH2:16][CH2:17]1Participants
Procedure
The title compound was prepared according to the procedure from Example 4, step (c) using 2-cyano-5-furancarboxylic acid (as prepared in Example 1) and 4-methyl-6′-(4-methyl-piperazin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3′-ylamine (as prepared in the previous step). Purification of the resulting residue by silica gel preparative TLC eluting with 10% methanol in dichloromethane afforded the title compound in 50% as a yellow glass. 1H-NMR (400 MHz, CDCl3): δ 8.76 (br s, 1H), 8.410 (d, 1H, J=8.8 Hz), 7.24 (d, 1H, J=3.7 Hz), 7.21 (d, 1H, J=3.7 Hz), 6.37 (d, 1H, J=8.8 Hz), 3.53 (m, 4H), 3.21-3.18 (m, 2H), 2.85 (m, 2H), 2.52 (m, 4H), 2.34 (s, 3H), 1.82-1.79 (m, 2H), 1.57 (m, 1H), 1.47-1.37 (m, 2H) 1.05 (d, 3H, J=6.5 Hz). NOE 1H-NMR experiments confirmed the correct regiochemical assignment. LC-MS (ESI, m/z): Calcd. for C22H29N6O2, 409.2 (M+H); found: 409.2.
Workup
- customThe title compound was prepared
- customas prepared in the previous step)
- customPurification of the resulting residue by silica gel preparative TLC
- washeluting with 10% methanol in dichloromethane
Sources & evidence
- ORD record
- ord-7226c84f2c464cfe8310faa7184c59ca
- Source dataset
- uspto-grants-2010_04
- Patent number
- US07705042B2
Reaction notes
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