Boron tribromide → HCID 86722366, Verbindung

HRID 718779Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 718779
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

Komponenten

4

Edukt 2

HCID 25134Boron tribromideHCID 86722365HCID 86722365, Verbindung

Produkt 1

HCID 86722366HCID 86722366, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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)

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-f98f7855a97c45fd8225371713e2028e
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193744B2

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