Hydrochloric Acid → HCID 178455649, compound

HRID 639428Notes

Reaction equation

HRID 639428 reaction equation
Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(S(NC1CCC(C(O)=O)CC1)(=O)=O)(C)(C)C.FC(F)(F)C1C=CC(N)=C(N)C=1.[NH2:52][C:53]1[CH:58]=[CH:57][C:56]([C:59]([F:62])([F:61])[F:60])=[CH:55][C:54]=1[NH:63][C:64]([C@H:66]1[CH2:71][CH2:70][C@H:69]([NH:72][S:73]([C:76]([CH3:79])([CH3:78])[CH3:77])(=[O:75])=[O:74])[CH2:68][CH2:67]1)=O.P(Cl)(Cl)(Cl)=O>C(OCC)(=O)C.CN(C=O)C>[C:76]([S:73]([NH:72][C@H:69]1[CH2:68][CH2:67][C@H:66]([C:64]2[NH:63][C:54]3[CH:55]=[C:56]([C:59]([F:61])([F:62])[F:60])[CH:57]=[CH:58][C:53]=3[N:52]=2)[CH2:71][CH2:70]1)(=[O:75])=[O:74])([CH3:79])([CH3:78])[CH3:77]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 24813Phosphorus oxychlorideHCID 757711-HydroxybenzotriazoleHCID 5208224-Trifluoromethyl-1,2-phenylenediamineHCID 118426424-[(2-Methylpropane-2-sulfonyl)amino]cyclohexane-1-carboxylic acidHCID 178455653HCID 178455653, compound

Product 1

HCID 178455649HCID 178455649, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodimide (87 mg) and 1-hydroxybenzotriazole (90 mg) were added to a DMF solution (4.0 mL) containing 4-tert-butylsulfonylaminocyclohexanecarboxylic acid (99 mg) as prepared by the above-described preparation method and 4-trifluoromethyl-1,2-phenylenediamine (66 mg), followed by stirring at room temperature for 16 hrs. The reaction solution was diluted with ethyl acetate, and the organic layer was washed with aqueous saturated sodium hydrogencarbonate and sodium chloride solutions, successively, dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give a crude amide containing trans-N-(2-amino-5-trifluoromethylphenyl)-4-tertbutylsulfonylaminocyclohexanecarboxamide. The crude amide was admixed with phosphorus oxychloride (1.0 mL), and the mixture was heated under stirring at 100° C. for 2 hrs. The excess phosphorus oxychloride was distilled off under reduced pressure, and the residue was diluted with ethyl acetate. The organic layer was washed with aqueous saturated sodium hydrogencarbonate and sodium chloride solutions successively, dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was crystallized from isopropyl ether to give the title compound (48.2 mg).

Workup

  1. washthe organic layer was washed with aqueous saturated sodium hydrogencarbonate and sodium chloride solutions
  2. dry with materialsuccessively, dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give a crude amide
  5. temperaturethe mixture was heated
  6. stirringunder stirring at 100° C. for 2 hrs
  7. distillationThe excess phosphorus oxychloride was distilled off under reduced pressure
  8. additionthe residue was diluted with ethyl acetate
  9. washThe organic layer was washed with aqueous saturated sodium hydrogencarbonate and sodium chloride solutions successively
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customthe residue was crystallized from isopropyl ether

Sources & evidence

ORD record
ord-1c39515e3904481ba2565133325c9663
Source dataset
uspto-grants-2010_04
Patent number
US07691860B2

Reaction notes

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