Boron tribromide → HCID 86722366, 화합물

HRID 718779노트

반응식

HRID 718779 반응식
C([O:8][C@@:9]1([C:42]([F:45])([F:44])[F:43])[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][N:35]2[CH2:39][CH2:38][CH2:37][S:36]2(=[O:41])=[O:40])[CH2:11][CH2:10]1)C1C=CC=CC=1.B(Br)(Br)Br>C(Cl)Cl>[F:32][C:29]1[CH:28]=[CH:27][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:42]([F:45])([F:43])[F:44])[CH2:10][CH2:11][C@@:12]5([CH2:34][N:35]5[CH2:39][CH2:38][CH2:37][S:36]5(=[O:40])=[O:41])[C:18]4=[CH:19][C:20]=3[CH:21]=[N:22]2)=[CH:31][CH:30]=1

참가 물질

4

반응물 2

HCID 25134Boron tribromideHCID 86722365HCID 86722365, 화합물

생성물 1

HCID 86722366HCID 86722366, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of 2-(((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)isothiazolidine 1,1-dioxide (35, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rg=Benzyl) (63 mg, 0.10 mmol) in DCM (3 mL) was cooled to about 0° C. and treated with BBr3 (0.40 mL, 0.40 mmol). The mixture was stirred for about 30 min, then the reaction was quenched by dropwise addition of MeOH (5 mL) and warmed to rt. The reaction was concentrated under reduced pressure, then dissolved in MeOH (5 mL) and stirred at 35° C. for about 15 min. DCM (5 mL) was added and the mixture was concentrated onto silica gel (1 g). The residue was purified on silica gel column (4 g) using a gradient of 30-100% EtOAc in DCM. Product fractions were combined and concentrated. The residue was dissolved in MeOH (5 mL) and water (3 mL), then concentrate under reduced pressure to about (3 mL) volume. The product was filtered off and dried under reduced pressure to yield 2-(((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)isothiazolidine 1,1-dioxide (11, R1=4-Fluorophenyl, R2=1,1-dioxidoisothiazolidin-2-yl)methyl, R3=Trifluoromethyl) (22 mg, 41%) as an off-white solid; LC/MS, method 2, Rt=2.59 min, MS m/z 552 (M+H)+, 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H), 7.90 (s, 1H), 7.85-7.76 (m, 2H), 7.62 (s, 1H), 7.45-7.37 (m, 2H), 5.98 (s, 1H), 3.65 (q, J=14.6 Hz, 2H), 3.41-3.32 (m, 1H), 3.14-2.99 (m, 2H), 2.96-2.86 (m, 1H), 2.36-2.25 (m, 1H), 2.20-2.08 (m, 1H), 2.08-1.55 (m, 12H), 1.49-1.35 (m, 1H). (Example 75)

후처리

  1. customthe reaction was quenched by dropwise addition of MeOH (5 mL)
  2. concentrationThe reaction was concentrated under reduced pressure
  3. dissolutiondissolved in MeOH (5 mL)
  4. stirringstirred at 35° C. for about 15 min
  5. additionDCM (5 mL) was added
  6. concentrationthe mixture was concentrated onto silica gel (1 g)
  7. customThe residue was purified on silica gel column (4 g)
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in MeOH (5 mL)
  10. concentrationwater (3 mL), then concentrate under reduced pressure to about (3 mL) volume
  11. filtrationThe product was filtered off
  12. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-f98f7855a97c45fd8225371713e2028e
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193744B2

반응 노트

불러오는 중…