1-Hydroxybenzotriazole → Artelinate

HRID 553405Notes

Reaction equation

HRID 553405 reaction equation
C[C@H]1[C@@H]2CCC3(C)OO[C@]42[C@H]([C@@H](C)[C@@H](O)O[C@@H]4O3)CC1.[CH3:21][C@@H:22]1[C@H:31]2[CH2:32][CH2:33][C@@:34]3([CH3:38])[O:36][O:37][C@@:30]42[C@H:25]([C@H:26]([CH3:50])[C@H:27]([O:39][CH2:40][C:41]2[CH:42]=[CH:43][C:44]([C:47]([OH:49])=[O:48])=[CH:45][CH:46]=2)[O:28][C@@H:29]4[O:35]3)[CH2:24][CH2:23]1.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)(C)C)C>C(#N)C>[CH3:21][C@H:22]1[C@@H:31]2[CH2:32][CH2:33][C:34]3([CH3:38])[O:36][O:37][C@:30]42[C@H:25]([C@@H:26]([CH3:50])[C@@H:27]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]([OH:49])=[O:48])=[CH:43][CH:42]=2)[O:28][C@@H:29]4[O:35]3)[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 456410Npc182939HCID 45940091-tert-Butyl-3-ethylcarbodiimideHCID 717190354-[[(1R,4R,5S,8S,9S,10R,12R,13S)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]benzoic acid

Product 1

HCID 73156Artelinate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Attempts to prepare an hydrazide derivative of artesunate were unsuccessful and resulted in the formation of dihydroartemisinin due to the cyclization reaction. Artelinate was synthesized from dihydroartemisinin as previously described (Shrimali et al. (1998) Indian J. Chem. 37B:1161-1163). Artelinic acid (0.1 g, 0.24 mmol) was dissolved in anhydrous acetonitrile (0.48 mL). To this solution, 1-hydroxybenztriazole (HOBt) (0.038 g, 0.29 mmol) was added, followed by addition of ethyl dimethylethylcarbodiimide (0.055 g, 0.29 mmol). The reaction mixture was stirred at room temperature and monitored by thin-layer chromatography (TLC) until all the acid was converted to the HOBt ester.

Sources & evidence

ORD record
ord-c3defc15bea949658fc4a5ffc314abb0
Source dataset
uspto-grants-2011_11
Patent number
US08048850B2

Reaction notes

Loading…