Hydrochloric Acid → HCID 178447013, 화합물

반응식

[CH3:1][O:2][CH2:3][C:4]([C:7]1[CH:44]=[CH:43][C:10]2[NH:11][C:12]([CH2:14][CH2:15][CH:16]3[CH2:19][CH:18]([N:20]([CH2:22][C@@H:23]4[C@H:27]5[O:28]C(C)(C)[O:30][C@H:26]5[C@H:25]([N:33]5[CH:41]=[N:40][C:39]6[C:34]5=[N:35][CH:36]=[N:37][C:38]=6[NH2:42])[O:24]4)[CH3:21])[CH2:17]3)=[N:13][C:9]=2[CH:8]=1)([CH3:6])[CH3:5].Cl.[CH3:46]O>>[NH2:42][C:38]1[N:37]=[CH:36][N:35]=[C:34]2[C:39]=1[N:40]=[CH:41][N:33]2[C@H:25]1[C@H:26]([OH:30])[C@H:27]([OH:28])[C@@H:23]([CH2:22][N:20]([CH:18]2[CH2:19][CH:16]([CH2:15][CH2:14][C:12]3[NH:11][C:10]4[CH:43]=[CH:44][C:7]([C:4]([CH2:5][CH3:46])([CH3:6])[CH2:3][O:2][CH3:1])=[CH:8][C:9]=4[N:13]=3)[CH2:17]2)[CH3:21])[O:24]1

참가 물질

반응물 3

HCID 313Hydrochloric Acid

HCID 887Methanol

HCID 178494914HCID 178494914, 화합물

생성물 1

HCID 178447013HCID 178447013, 화합물수율 53%

실험 절차

9-[(3aR,4R,6R,6aR)-6-{[(3-{2-[5-(1-Methoxy-2-methylpropan-2-yl)-1H-1,3-benzodiazol-2-yl]ethyl}cyclobutyl)(methyl)amino]methyl}-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-amine (0.485 g, 0.706 mmol, 88% pure) was dissolved in MeOH (20 ml) and cone. HCl (4.9 ml, 10 vol) was added at r.t. and the reaction left for 2.5 h. The reaction was concentrated in vacuo and the residue dissolved in the minimum amount of MeOH (˜2 ml). The reaction was quenched by addition of sat. NaHCO3 solution (10 ml) and EtOAc (30 ml). The layers were separated and the aqueous layer was extracted with EtOAc (2×30 ml). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give the crude product. The product was purified by silica flash column chromatography using between 100% DCM and 20% 2M NH3 in MeOH:80% DCM as eluent to give the product as a white foam (0.213 g, 53%): MS (ESI+) for C29H40N8O4 m/z 565.4[M+H]+; LC purity 100% (ret. time, 2.11 min) (7 min); 1H NMR (500 MHz, d4-MeOD) δH 8.28 (d, J=4.1 Hz, 1H), 8.22 (d, J=3.2 Hz, 1H), 7.51 (s, 1H), 7.42 (dd, J=8.5, 2.1 Hz, 1H), 7.29 (dd, J=8.5, 1.5 Hz, 1H), 6.01 (t, J=3.9 Hz, 1H), 4.84-4.74 (m, 1H), 4.41-4.29 (m, 1H), 4.29-4.19 (m, 1H), 3.48 (s, 2H), 3.30 (s, 3H), 3.14-2.98 (m, 1H), 2.99-2.89 (m, 1H), 2.90-2.73 (m, 2H), 2.39 (s, 3H), 2.37-2.30 (m, 1H), 2.28-2.10 (m, 2H), 2.08-1.86 (m, 4H), 1.70-1.51 (m, 1H), 1.38 (s, 6H).