2-((Dimethylamino)methyl)prop-2-enoic acid → 2-[(dimethylamino)methyl]-N-[2-hydroxy-4-[[[(Z)-(6-iodo-1,3-dioxoisoquinolin-4-ylidene)methyl]amino]methyl]phenyl]prop-2-enamide
Reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9]/[CH:10]=[C:11]2\[C:12](=[O:23])[NH:13][C:14](=[O:22])[C:15]3[C:20]\2=[CH:19][C:18]([I:21])=[CH:17][CH:16]=3)[CH:5]=[CH:4][C:3]=1[NH:24][C:25](=[O:30])/[C:26](/[CH3:29])=[CH:27]/C.NC1C=CC([CH2:36][NH:37]/[CH:38]=C2\C(=O)NC(=O)C3C\2=CC(I)=CC=3)=CC=1O[Si](C(C)C)(C(C)C)C(C)C.CN(CC(=C)C(O)=O)C>>[CH3:36][N:37]([CH2:29][C:26](=[CH2:27])[C:25]([NH:24][C:3]1[CH:4]=[CH:5][C:6]([CH2:8][NH:9]/[CH:10]=[C:11]2\[C:12](=[O:23])[NH:13][C:14](=[O:22])[C:15]3[C:20]\2=[CH:19][C:18]([I:21])=[CH:17][CH:16]=3)=[CH:7][C:2]=1[OH:1])=[O:30])[CH3:38]Participants
Procedure
Following the acetylation and desilylation procedure employed for the preparation of (2E)-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2-methylbut-2-enamide, (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg, 0.11 mmol) is reacted with acid chloride derived from 2-dimethylaminomethyl acrylic acid (Wissner, A.; Overbeek, E.; Reich, M. F.; Floyd, M. B.; Johnson, B. D.; Mamuya, N.; Rosfjord, E. C.; Discafani, C.; Davis, R.; Shi, X.; Rabindran, S. K.; et al. J. Med. Chem. 46; 1; 2003; 49-63, 0.18 g, 1.1 mmol). Following desilylation and precipitation, 2-[(dimethylamino)methyl]-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide is obtained as a solid (19 mg, 32%).
Workup
- customdesilylation and precipitation
Sources & evidence
- ORD record
- ord-1329d681f40441db8d18696e15d54864
- Source dataset
- uspto-grants-2010_05
- Patent number
- US07713994B2
Reaction notes
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