Methanesulfonic Acid → 8-{[(2S)-2-(Hydroxymethyl)pyrrolidin-1-yl]sulfonyl}-3,3-dimethyl-3,4-dihydropyrimido[1,2-a]indol-10(2H)-one

반응식

C([O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[S:15]([C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][C:28]([CH3:32])([CH3:31])[CH2:29][N:30]=[C:22]3[C:21]3(OCCC[O:33]3)[C:20]=2[CH:19]=1)(=[O:17])=[O:16])C1C=CC=CC=1.CS(O)(=O)=O.[NH4+].[OH-]>>[OH:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[S:15]([C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][C:28]([CH3:31])([CH3:32])[CH2:29][N:30]=[C:22]3[C:21](=[O:33])[C:20]=2[CH:19]=1)(=[O:16])=[O:17]

참가 물질

반응물 3

HCID 6395Methanesulfonic Acid

HCID 14923Ammonium Hydroxide

HCID 115989258'-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)-3',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indole]

생성물 1

HCID 115381048-{[(2S)-2-(Hydroxymethyl)pyrrolidin-1-yl]sulfonyl}-3,3-dimethyl-3,4-dihydropyrimido[1,2-a]indol-10(2H)-one수율 78%

실험 절차

To neat 8′-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)-3′,3′-dimethyl-3′,4′-dihydro-2′H-spiro[1,3-dioxane-2,10′-pyrimido[1,2-a]indole] (0.500 g, 0.951 mmol) was added methane sulfonic acid (24 mL) all at one time at room temperature. After 5 hr the reaction mixture was poured onto ice and basified to pH 11.2 by the drop-wise addition of concentrated NH4OH keeping the temperature below 5° C. The reaction was extracted with EtOAc (5×). The combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (94.75/3.5/1.75) to give the title compound as a bright orange solid (0.28 g, 68% yield). A 100 mg sample was dried at 63° C. in vacuo to give the analytically pure sample. Anal. Calc'd for; C18H23N3O4S: C, 57.28; H, 6.14; N, 11.13. Found: C, 57.05; H, 5.99; N, 10.79. NMR (400 MHz, DMSO-d6): consistent. MS: (ES+) m/z 378 [M+H]. m.p.: 91-96° C. dec.