N-bromobutanimide → HCID 86722387, compound

HRID 718789Notes

Reaction equation

HRID 718789 reaction equation
C1C(=O)N([Br:8])C(=O)C1.[CH2:9]([C@:11]12[CH2:35][CH2:34][C@@:33]([C:37]([F:40])([F:39])[F:38])([OH:36])[CH2:32][C@H:12]1[CH2:13][CH2:14][CH2:15][C:16]1[C:17]2=[CH:18][C:19]2[CH:20]=[N:21][N:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:23]=2[CH:24]=1)[CH3:10]>CN(C=O)C>[Br:8][C:24]1[C:23]2[N:22]([C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[N:21]=[CH:20][C:19]=2[CH:18]=[C:17]2[C@@:11]3([CH2:9][CH3:10])[CH2:35][CH2:34][C@@:33]([C:37]([F:40])([F:39])[F:38])([OH:36])[CH2:32][C@H:12]3[CH2:13][CH2:14][CH2:15][C:16]=12

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 74221111HCID 74221111, compound

Product 1

HCID 86722387HCID 86722387, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NBS (0.011 g, 0.064 mmol) was added to a solution of (3R,4aR,12bS)-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (15, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.022 g, 0.049 mmol) in DMF (0.5 mL) and the mixture was heated to about 60° C. for about 3 h. After cooling to rt, the reaction was quenched with ice (5 g). Sat. Aq. Na2CO3 (10 mL) and EtOAc (20 mL) were added. The layers were separated and the organic layer was washed with water (10 mL) then dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (4 g) using a gradient of 0-27% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure. The residue was lyophilized to yield (3R,4aR,12bS)-8-bromo-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (46, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.013 g, 49% yield); LC/MS, method 2, Rt=3.13 min.; MS m/z: 525 and 527 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H), 7.90 (s, 1H), 7.57-7.50 (m, 2H), 7.38-7.30 (m, 2H), 5.56 (s, 1H), 3.56-3.44 (m, 1H), 3.03-2.88 (m, 1H), 2.43-2.18 (m, 2H), 2.16-1.66 (m, 7H), 1.64-1.38 (m, 4H), 0.68 (t, J=7.3 Hz, 3H).

Workup

  1. customthe reaction was quenched with ice (5 g)
  2. additionSat. Aq. Na2CO3 (10 mL) and EtOAc (20 mL) were added
  3. customThe layers were separated
  4. washthe organic layer was washed with water (10 mL)
  5. dry with materialthen dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on silica gel (4 g)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-077f82100e8348e5b2c830d6d7243aa8
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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