[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C@H:12]([N:15]([CH3:45])[C@@H:16]2[CH2:23][N:22]3[C:24]4[CH:25]=[C:26]([C:37](OC)=[O:38])[CH:27]=[CH:28][C:29]=4[C:30]([CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[C:21]3[C:20]3[CH:41]=[CH:42][CH:43]=[CH:44][C:19]=3[O:18][CH2:17]2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl.C(Cl)CCl.[CH3:51][O:52][CH:53]([O:61][CH3:62])[CH2:54][N:55]([CH3:60])[S:56]([NH2:59])(=[O:58])=[O:57]>O1CCOCC1.C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:31]1([C:30]2[C:29]3[CH:28]=[CH:27][C:26]([C:37]([NH:59][S:56]([N:55]([CH2:54][CH:53]([O:52][CH3:51])[O:61][CH3:62])[CH3:60])(=[O:58])=[O:57])=[O:38])=[CH:25][C:24]=3[N:22]3[C:21]=2[C:20]2[CH:41]=[CH:42][CH:43]=[CH:44][C:19]=2[O:18][CH2:17][C@H:16]([N:15]([CH3:45])[C@H:12]2[CH2:13][CH2:14][N:10]([C:8]([O:7][C:3]([CH3:4])([CH3:6])[CH3:5])=[O:9])[CH2:11]2)[CH2:23]3)[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]11M KOH (3.5 eq) was added to a 0.3M solution of methyl (7R)-7-[[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (1 eq) in dioxane and the mixture was stirred at 75° C. for 12 h. The pH was adjusted at 0° C. by addition of 1N HCl (until pH=6), then all volatiles were evaporated, the solid residue was taken in CHCl3 and salt was filtered off. The filtrate was concentrated in vacuo to afford a residue that was taken in dry DCM (0.05M); DMAP (3.5 eq), EDC (1.5 eq) and N-(2,2-dimethoxyethyl)-N-methylsulfamide (1.5 eq; prepared as described in Example 1, step 1) were added and the mixture was stirred at 40° C. for 1 h. The residue obtained after evaporation was extracted with EtOAc. The combined organic phases were washed with 1M HCl, sat. aq. NaHCO3 and brine, dried over Na2SO4 and concentrated to afford the title compound which was used without further purification. (ES+) m/z 754 (M+H)+.
불러오는 중…