Triethylamine → HCID 178519654, compound

HRID 1013842Notes

Reaction equation

HRID 1013842 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([Cl:31])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C@H:14]2[CH2:22][CH2:21][C:20]3[C:16](=[CH:17][N:18](S(C(F)(F)F)(=O)=O)[N:19]=3)[CH2:15]2)[C:10]1=[O:30].Cl.[F:41][C:42]([F:50])([F:49])[CH:43]1CCNCC1.[CH2:51]([N:53]([CH2:56][CH3:57])[CH2:54][CH3:55])C.[C]=[O:59]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C)C=O>[Cl:31][C:6]1[CH:5]=[C:4]([C:51]([N:53]2[CH2:56][CH2:57][CH:43]([C:42]([F:50])([F:49])[F:41])[CH2:55][CH2:54]2)=[O:59])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C@H:14]2[CH2:22][CH2:21][C:20]3[C:16](=[CH:17][NH:18][N:19]=3)[CH2:15]2)[C:10]1=[O:30]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 87354083HCID 87354083, compoundHCID 178418416HCID 178418416, compound2×

Product 1

HCID 178519654HCID 178519654, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

Dissolve (3R,5S)-Trifluoro-methanesulfonic acid 3,5-dichloro-4-[2-oxo-1-(2-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (Preparation 43) (0.307 g, 0.48 mmol) in 5 ml of argon-sparged toluene. Treat with 4-trifluoromethylpiperidine-HCl salt (0.27 g, 1.43 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (0.02 g, 0.024 mmol) and triethylamine (0.21 ml, 1.48 mmol). Stir under 48 psi carbon monoxide pressure at 80° C. for 4 hr. Add 3 ml of argon-sparged dimethyl formamide and more triethylamine (0.25 ml, 1.76 mmol). Heat at 80° C. for 5 hrs under 50 psi carbon monoxide pressure. LCMS shows consumption of starting material. Cool to ambient temperature and add ethyl acetate (50 ml) and water (10 ml). Extract the aqueous phase with ethyl acetate (50 ml). Wash the organic phases with water (10 ml) and brine (10 ml). Combine the organic phases, dry over sodium sulfate and concentrate under reduced pressure. Dissolve the crude product in 5 ml of dimethoxyethane and treat with 2 M aqueous lithium hydroxide solution (1 ml). Stir for 2 hrs at ambient temperature. Dilute with ethyl acetate (50 ml) and water (10 ml) and extract the aqueous phase with ethyl acetate (50 ml). Wash the organic phases with water (10 ml) and brine (10 ml). Combine the organic phases, dry over sodium sulfate and concentrate under reduced pressure. Chromatography (silica, 97:3 CH2Cl2/2M NH3 in MeOH) yields 0.080 g as a white solid MS (m/z): 543 (M+1).

Workup

  1. customsparged toluene
  2. additionAdd 3 ml of argon-
  3. customconsumption of starting material
  4. additionadd ethyl acetate (50 ml) and water (10 ml)
  5. extractionExtract the aqueous phase with ethyl acetate (50 ml)
  6. washWash the organic phases with water (10 ml) and brine (10 ml)
  7. dry with materialCombine the organic phases, dry over sodium sulfate
  8. concentrationconcentrate under reduced pressure
  9. dissolutionDissolve the crude product in 5 ml of dimethoxyethane
  10. additiontreat with 2 M aqueous lithium hydroxide solution (1 ml)
  11. additionDilute with ethyl acetate (50 ml) and water (10 ml)
  12. extractionextract the aqueous phase with ethyl acetate (50 ml)
  13. washWash the organic phases with water (10 ml) and brine (10 ml)
  14. dry with materialCombine the organic phases, dry over sodium sulfate
  15. concentrationconcentrate under reduced pressure
  16. customChromatography (silica, 97:3 CH2Cl2/2M NH3 in MeOH) yields 0.080 g as a white solid MS (m/z)

Sources & evidence

ORD record
ord-cdc21a29b1214a58a56b013ad83ca458
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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