Boron tribromide → HCID 74220524, Verbindung
Reaktionsgleichung
C([O:8][C@@:9]1([C:40]([F:43])([F:42])[F:41])[CH2:33][C@H:13]2[CH2:14][CH2:15][CH2:16][C:17]3[C:18](=[CH:19][C:20]4[CH:21]=[N:22][N:23]([C:26]5[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=5)[C:24]=4[CH:25]=3)[C@:12]2([CH2:34][NH:35][S:36]([CH3:39])(=[O:38])=[O:37])[CH2:11][CH2:10]1)C1C=CC=CC=1.B(Br)(Br)Br>C(Cl)Cl>[F:32][C:29]1[CH:30]=[CH:31][C:26]([N:23]2[C:24]3[CH:25]=[C:17]4[CH2:16][CH2:15][CH2:14][C@@H:13]5[CH2:33][C@@:9]([OH:8])([C:40]([F:42])([F:41])[F:43])[CH2:10][CH2:11][C@@:12]5([CH2:34][NH:35][S:36]([CH3:39])(=[O:37])=[O:38])[C:18]4=[CH:19][C:20]=3[CH:21]=[N:22]2)=[CH:27][CH:28]=1Komponenten
4
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Versuchsvorschrift
A solution of N-(((3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)methanesulfonamide (35, R1=4-Fluorophenyl, R3=Trifluoromethyl, R4=Methanesulfonyl, Rx=Benzyl) (40 mg, 0.065 mmol) in DCM (3 mL) was cooled to about 0° C. and treated with BBr3 (1M in hexane, 0.23 mL, 0.23 mmol). The mixture was stirred for about 30 min at rt. The reaction was quenched by addition of MeOH (5 mL) and warmed to rt for about 90 min. Solvents were removed under reduced pressure and the residue was dissolved in DCM (20 mL) and concentrated onto silica gel (1 g). The residue was purified on silica gel (12 g) using a gradient of 30-100% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure. The residue was dissolved in MeOH (5 mL), diluted with water (3 mL) and reduced in volume to about 3 mL under reduced pressure. The product was filtered off and dried under vacuum at about 50° C. to yield N-(((3R,4aR,12bS)-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)methanesulfonamide (36, R1=4-Fluorophenyl, R3=Trifluoromethyl, R4=Methanesulfonyl) (23 mg, 67%) as an off-white solid. LC/MS, method 2, Rt=2.49 min, MS m/z 526 (M+H)+, 1H NMR (400 MHz, DMSO) δ 8.25 (d, J=0.6 Hz, 1H), 7.84 (s, 1H), 7.79-7.72 (m, 2H), 7.55 (s, 1H), 7.42-7.34 (m, 2H), 6.29 (t, J=6.7 Hz, 1H), 5.89 (s, 1H), 3.90-3.81 (m, 1H), 3.36-3.30 (m, 1H), 3.28-3.20 (m, 1H), 3.00-2.90 (m, 1H), 2.61 (s, 3H), 2.28-2.20 (m, 1H), 2.14-2.03 (m, 1H), 2.02-1.73 (m, 5H), 1.72-1.53 (m, 3H), 1.44-1.30 (m, 1H).