Boron trifluoride → [3-Hydroxy-5-(1H-indol-4-yl)phenyl](6-methoxy-3-pyridinyl)methanone

HRID 1784833Notes

Reaction equation

HRID 1784833 reaction equation
COC1C=CC(C[O:8][C:9]2[CH:10]=[C:11]([C:34]([C:36]3[CH:37]=[N:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=3)=[O:35])[CH:12]=[C:13]([C:15]3[CH:23]=[CH:22][CH:21]=[C:20]4[C:16]=3[CH:17]=[CH:18][N:19]4[Si](C(C)C)(C(C)C)C(C)C)[CH:14]=2)=CC=1.B(F)(F)F.CCOC(C)=O.C([O-])(O)=O.[Na+]>CSC>[OH:8][C:9]1[CH:10]=[C:11]([C:34]([C:36]2[CH:37]=[N:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)=[O:35])[CH:12]=[C:13]([C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH:17]=[CH:18][NH:19]3)[CH:14]=1

Participants

6

Reactant 4

HCID 6356Boron trifluorideHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 68842123HCID 68842123, compound

Product 1

HCID 15602887[3-Hydroxy-5-(1H-indol-4-yl)phenyl](6-methoxy-3-pyridinyl)methanoneYield 75%

Reagents, catalysts & solvents 1

HCID 1068Dimethyl SulfideSolvent

Conditions

Temperature
0 °C

Procedure

To compound [3-(4-methoxy-benzyloxy)-5-(1-triisopropylsilanyl-1H-indol-4-yl)-phenyl]-(6-methoxy-pyridin-3-yl)-methanone in dimethylsulfide (2 mL) at 0° C. was added excess BF3 etherate. The resulting reaction mixture was stirred at 0° C. for 20 min. TLC indicated that the disappearance of the starting material. EtOAc was added to dilute the reaction mixture and sat. NaHCO3 was added to adjust the pH of the aqueous phase to 6-7. The aqueous phase was then extracted with EtOAc three times. The combined organic phases were dried over Na2SO4 and concentrated. The crude product was again dissolved in THF (1 mL) and treated with TBAF (1M in THF, 1 mL) at 0° C. The reaction mixture was allowed to warm up to room temperature. At the end of the reaction, the solvent was removed under reduced pressure. The residue was dissolved in EtOAc and washed with water three times. The organic phase was then dried and concentrated to afford the crude product which was further purified by preparative SFC to afford [3-hydroxy-5-(1H-indol-4-yl)-phenyl]-(6-methoxy-pyridin-3-yl)-methanone (29 mg, 75%). 1H NMR (400 MHz, CD3OD): δ 8.57 (d, J=2.3 Hz, 1H), 8.04 (dd, J=8.6, 2.3 Hz, 1H), 7.42 (d, J=1.2 Hz, 1H), 7.36-7.30 (m, 2H), 7.17 (d, J=3.1 Hz, 1H), 7.12-7.08 (m, 2H), 7.03 (d, J=7.2 Hz, 1H), 6.76 (d, J=8.6 Hz, 1H), 6.55 (d, J=2.5 Hz, 1H), 3.90 (s, 3H).

Workup

  1. customThe resulting reaction mixture
  2. additionwas added
  3. extractionThe aqueous phase was then extracted with EtOAc three times
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe crude product was again dissolved in THF (1 mL)
  7. additiontreated with TBAF (1M in THF, 1 mL) at 0° C
  8. temperatureto warm up to room temperature
  9. customAt the end of the reaction
  10. customthe solvent was removed under reduced pressure
  11. dissolutionThe residue was dissolved in EtOAc
  12. washwashed with water three times
  13. customThe organic phase was then dried
  14. concentrationconcentrated
  15. customto afford the crude product which
  16. customwas further purified by preparative SFC

Sources & evidence

ORD record
ord-bf7c1aa2d4904ff2b4fe22d102d65b39
Source dataset
uspto-grants-2009_03
Patent number
US07504401B2

Reaction notes

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