Oxalyl chloride → HCID 178480681, compound

HRID 1526041Notes

Reaction equation

HRID 1526041 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[C:11]([N:18]([C@H:25]3[CH2:30][CH2:29][C@@H:28]([O:31]C(C4C=CC=CC=4)=O)[CH2:27][CH2:26]3)C(=O)C(F)(F)F)[CH:10]=2)[CH2:5][CH2:4]1.C(Cl)(=O)C(Cl)=O.[F:46][C:47]1[CH:48]=[C:49]([CH:61]=[C:62]([F:64])[CH:63]=1)[CH2:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][CH:59]=1)[NH:56][N:55]=[C:54]2[NH2:60].O[Li].O>C(Cl)Cl.N1C=CC=CC=1.CO.O>[F:46][C:47]1[CH:48]=[C:49]([CH:61]=[C:62]([F:64])[CH:63]=1)[CH2:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][CH:59]=1)[NH:56][N:55]=[C:54]2[NH:60][C:13](=[O:14])[C:12]1[CH:16]=[CH:17][C:9]([N:6]2[CH2:7][CH2:8][N:3]([CH3:2])[CH2:4][CH2:5]2)=[CH:10][C:11]=1[NH:18][C@H:25]1[CH2:30][CH2:29][C@@H:28]([OH:31])[CH2:27][CH2:26]1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amineHCID 178480699HCID 178480699, compound

Product 1

HCID 178480681HCID 178480681, compoundYield 27.2%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

4-(4-methylpiperazin-1-yl)-2-[{cis-4-[(phenylcarbonyl)oxy]cyclohexyl}(trifluoroacetyl)amino]benzoic acid hydrochloride (1.03 gr, 1.94 mmol) and oxalyl chloride (3.88 mmol) were stirred in DCM dry (20 mL) and a few drops of dry DMF at 0° C., temperature was allowed to reach room temperature in 2 hours. Volatiles were evaporated and the residue dissolved in dry pyridine (25 mL) at 0° C. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (387 mg, 1.49 mmol) in dry pyridine (6 mL) was added to the cooled reaction mixture. Temperature was allowed to reach room temperature overnight. Reaction was quenched with NaHCO3 sat. sol and extracted with ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/AcOEt/EtOH=100/10/15). The so obtained derivative, was dissolved in MeOH (200 mL) and water (20 mL) and treated at 60° C. with LiOH hydrate (160 mg, 3.8 mmol) for 4 hours. MeOH was evaporated and the resulting aqueous phase was extracted with EtOAc. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=100/10/2) affording 233 mg of title compound.

Workup

  1. dry with materialdry (20 mL) and a few drops of dry DMF at 0° C.
  2. customVolatiles were evaporated
  3. dissolutionthe residue dissolved in dry pyridine (25 mL) at 0° C
  4. waitto reach room temperature overnight
  5. customReaction
  6. customwas quenched with NaHCO3 sat. sol
  7. extractionextracted with ethyl acetate
  8. dry with materialCollected organic phases were dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customResidue was purified by column chromatography over silica gel (DCM/AcOEt/EtOH=100/10/15)
  12. customThe so obtained derivative
  13. customMeOH was evaporated
  14. extractionthe resulting aqueous phase was extracted with EtOAc
  15. dry with materialCollected organic phases were dried over Na2SO4
  16. filtrationfiltered
  17. customevaporated to dryness
  18. customResidue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=100/10/2)

Sources & evidence

ORD record
ord-52f65d6756694932b28fcc720f8c9f3d
Source dataset
uspto-grants-2015_07
Patent number
US09085558B2

Reaction notes

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