Nicotinic Acid → 5,7-Dimethoxy-2-(4-(4-nicotinoylpiperazin-1-yl)phenyl)quinazolin-4(3H)-one
Reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(CC)CC.[CH3:39][O:40][C:41]1[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[C:47]2[C:42]=1[C:43](=[O:65])[NH:44][C:45]([C:53]1[CH:58]=[CH:57][C:56]([N:59]3[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]3)=[CH:55][CH:54]=1)=[N:46]2>C1COCC1>[CH3:39][O:40][C:41]1[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[C:47]2[C:42]=1[C:43](=[O:65])[NH:44][C:45]([C:53]1[CH:58]=[CH:57][C:56]([N:59]3[CH2:60][CH2:61][N:62]([C:1](=[O:9])[C:2]4[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=4)[CH2:63][CH2:64]3)=[CH:55][CH:54]=1)=[N:46]2Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of nicotinic acid (0.066 g, 0.54 mmol) in THF (20 mL) was added HOBt (0.079 g, 0.59 mmol), EDCl (0.113 g, 0.59 mmol), Et3N (0.08 mL, 0.59 mmol) and 5,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one (0.200 g, 0.54 mmol). The resulting solution was stirred overnight at room temperature. The solution was concentrated in vacuo and the resulting solid was purified by flash chromatography on silica gel, eluting with 10% to 60% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2, to afford the title compound (0.050 g, 19%): 1H NMR (300 MHz, DMSO-d6): δ 11.79 (s, 1H), 8.59-8.78 (m, 2H), 8.12 (d, J=8.8 Hz, 2H), 7.82-7.99 (m, 1H), 7.37-7.60 (m, 1H), 7.04 (d, J=9.1 Hz, 2H), 6.69 (s, 1H), 6.47 (s, 1H), 3.63-3.97 (m, 8H), 3.20-3.63 (m, 6H). APCI MS m/z 472 [M+H]+.
Workup
- concentrationThe solution was concentrated in vacuo
- customthe resulting solid was purified by flash chromatography on silica gel
- washeluting with 10% to 60% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2
Sources & evidence
- ORD record
- ord-59adb500ef044c888fb2267bb03cf32b
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09238640B2
Reaction notes
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