Triphenylphosphine → HCID 131726525, compound

HRID 1295686Notes

Reaction equation

HRID 1295686 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([F:9])=[C:4]([F:10])[C:3]=1[OH:11].C(OC([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[C:26]([O:31]CCO)=[N:27][CH:28]=[CH:29][N:30]=2)[CH2:21][CH2:20]1)=O)(C)(C)C.[C:35]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:36]=1.CN(C(/N=N/C(N(C)C)=O)=O)C.C(O)(C(F)(F)F)=O.[Cl:73]CCl.O>C1COCC1>[ClH:73].[N:22]1([C:25]2[C:26](=[O:31])[N:27]([CH2:35][CH2:36][O:11][C:3]3[C:2]([F:1])=[C:7]([F:8])[CH:6]=[C:5]([F:9])[C:4]=3[F:10])[CH:28]=[CH:29][N:30]=2)[CH2:21][CH2:20][NH:19][CH2:24][CH2:23]1

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 698582,3,5,6-TetrafluorophenolHCID 5353800DiamideHCID 114160742-[3-(4-Tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanolHCID 18672661HCID 18672661, compound

Product 1

HCID 131726525HCID 131726525, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,3,5,6-Tetrafluorophenol (556 mg, 3.35 mmol), 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-pyrazinyloxy]ethanol (1.01 g, 3.10 mmol) and triphenylphosphine (813 mg, 3.10 mmol) were dissolved in THF (10 mL) and TMAD (533 mg, 3.10 mmol) was added in three portions over 50 min. The reaction mixture was stirred at room temperature overnight. A small amount of a white precipitate was filtered off. The filtrate was evaporated, redissolved in ether and filtered again. The filtrate was washed with 5% NaHCO3 and brine, concentrated in vacuo, and the residue purified by flash chromatography using EtOAc/toluene (3:7 followed by 1:4) as eluent. This gave 584 mg (40%) of the title compound as its N-t-BOC derivative. The N-t-BOC intermediate (568 mg, 1.20 mmol) was treated with TFA/dichloromethane/H2O (42:53:5; 3.1 mL) at room temperature for 50 min with stirring. The solution was evaporated and the residue precipitated with MeOH-ether. This product was dissolved in 50% aqueous MeOH and passed through an anion exchange resin (Dowex-1 X8, Cl−, 4 g) eluting with 50% aqueous MeOH. Evaporation of the solvent in vacuum gave the title compound. Yield: 453 mg (92%); mp 196-198° C. (dec.); MS-EI m/z 372 (M)+; HRMS m/z calcd for C16H16F4N4O2 (M)+ 372.1209, found 372.1196. Anal. (C16H16F4N4O2.HCl) C, H, N.

Workup

  1. filtrationA small amount of a white precipitate was filtered off
  2. customThe filtrate was evaporated
  3. dissolutionredissolved in ether
  4. filtrationfiltered again
  5. washThe filtrate was washed with 5% NaHCO3 and brine
  6. concentrationconcentrated in vacuo
  7. customthe residue purified by flash chromatography
  8. stirringwith stirring
  9. customThe solution was evaporated
  10. customthe residue precipitated with MeOH-ether
  11. dissolutionThis product was dissolved in 50% aqueous MeOH
  12. washeluting with 50% aqueous MeOH
  13. customEvaporation of the solvent in vacuum

Sources & evidence

ORD record
ord-110efee81ef34ddc83aca78b943dee2d
Source dataset
uspto-grants-2007_07
Patent number
US07244722B2

Reaction notes

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