Boron tribromide → HCID 74220524, compound

HRID 718777Notes

Reaction equation

HRID 718777 reaction equation
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]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 86722364HCID 86722364, compound

Product 1

HCID 74220524HCID 74220524, compoundYield 67.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  1. customThe reaction was quenched by addition of MeOH (5 mL)
  2. temperaturewarmed to rt for about 90 min
  3. customSolvents were removed under reduced pressure
  4. dissolutionthe residue was dissolved in DCM (20 mL)
  5. concentrationconcentrated onto silica gel (1 g)
  6. customThe residue was purified on silica gel (12 g)
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in MeOH (5 mL)
  9. additiondiluted with water (3 mL)
  10. filtrationThe product was filtered off
  11. customdried under vacuum at about 50° C.

Sources & evidence

ORD record
ord-e05c94e0bb2c4406ae3a2049651bf83f
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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