3-fluoro-5-(3-methoxybenzoyl)-6-methyl-5,6-dihydrophenanthridine N-[1-(2',4'-difluoro-1,1'-biphenyl-2-yl)ethyl]-3-methoxybenzamide → 3-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]phenol

HRID 731986Notes

Reaction equation

HRID 731986 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:11]([CH:12]([CH3:26])[N:13]([C:16](=[O:25])[C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23]C)[CH:18]=4)[C:14]=2[CH:15]=1)=[CH:10][CH:9]=[CH:8][CH:7]=3.FC1C=C(F)C=CC=1C1C=CC=CC=1C(NC(=O)C1C=CC=C(OC)C=1)C>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:11]([CH:12]([CH3:26])[N:13]([C:16]([C:17]4[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=4)=[O:25])[C:14]=2[CH:15]=1)=[CH:10][CH:9]=[CH:8][CH:7]=3

Participants

3

Reactant 1

HCID 688184173-fluoro-5-(3-methoxybenzoyl)-6-methyl-5,6-dihydrophenanthridine N-[1-(2',4'-difluoro-1,1'-biphenyl-2-yl)ethyl]-3-methoxybenzamide

Product 1

HCID 115009123-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]phenolYield 85.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

3-fluoro-5-(3-methoxybenzoyl)-6-methyl-5,6-dihydrophenanthridine—N-[1-(2′,4′-difluoro-1,1′-biphenyl-2-yl)ethyl]-3-methoxybenzamide (1.29 g, 3.5 mmol) was dissolved in anhydrous THF (10 mL) and the vial was capped and purged with an inert atmosphere. Lithium bis(trimethylsilyl)amide (4.0 mL, 1 M in THF) was added to the solution and the mixture heated (70° C). The reaction progress was monitored by LCMS and heating was discontinued upon the expense of the starting material. The THF was removed and 2N aqueous HCl was added. The product was extracted with ethyl acetate (3×) and the combined organic phases were dried (Na2SO4), filtered, and concentrated to provide a crude oil. The residue was purified by flash column chromatography (Biotage® 40 Mi, 30-50% methyl tert-butylether in hexane) affording 1.0 g (82%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (d, J=6.76 Hz, 3 H) 3.71 (s, 3 H) 5.67 (s, 1 H) 6.77 (d, J=7.28 Hz, 2 H) 6.93 (s, 1 H) 7.03 (ddd, J=8.32, 2.73, 0.91 Hz, 1 H) 7.10 (td, J=8.71, 2.60 Hz, 1 H) 7.26 (t, J=7.93 Hz, 1 H) 7.40 (m, 3 H) 7.97 (d, J=7.54 Hz, 1 H) 8.01 (dd, J=8.84, 6.24 Hz, 1H); MS (ESI) m/z 348 ([M+H]+); HRMS: calcd for C22H18FNO2, 347.1322 (M), 348.13944 ([M+H]+); found (ESI_FT), 348.13903; Anal. Calcd for C22H18FNO2: C, 76.07; H, 5.22; N, 4.03. Found: C, 76.02; H, 5.32; N, 3.97.

Workup

  1. customthe vial was capped
  2. custompurged with an inert atmosphere
  3. additionLithium bis(trimethylsilyl)amide (4.0 mL, 1 M in THF) was added to the solution
  4. temperatureheating
  5. customThe THF was removed
  6. addition2N aqueous HCl was added
  7. extractionThe product was extracted with ethyl acetate (3×)
  8. dry with materialthe combined organic phases were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto provide a crude oil
  12. customThe residue was purified by flash column chromatography (Biotage® 40 Mi, 30-50% methyl tert-butylether in hexane)

Sources & evidence

ORD record
ord-3f35626f73a1433598f281c8a71e8b3c
Source dataset
uspto-grants-2009_09
Patent number
US07585871B2

Reaction notes

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