Propionyl chloride → 1-[4-(Cyanomethyl)-1-propanoylpiperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide

HRID 521239Notes

Reaction equation

HRID 521239 reaction equation
FC(F)(F)C([O-])=O.[C:8]([C:11]1[C:12]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:13][N:14]([C:16]2([CH2:22][C:23]#[N:24])[CH2:21][CH2:20][NH2+:19][CH2:18][CH2:17]2)[CH:15]=1)(=[O:10])[NH2:9].CCN(C(C)C)C(C)C.[C:41](Cl)(=[O:44])[CH2:42][CH3:43]>C1COCC1.CS(C)=O>[C:23]([CH2:22][C:16]1([N:14]2[CH:15]=[C:11]([C:8]([NH2:9])=[O:10])[C:12]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:13]2)[CH2:21][CH2:20][N:19]([C:41](=[O:44])[CH2:42][CH3:43])[CH2:18][CH2:17]1)#[N:24]

Participants

6

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 867293834-[4-Carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidinium trifluoroacetate

Product 1

HCID 867294141-[4-(Cyanomethyl)-1-propanoylpiperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-[4-carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-1) (50 mg, 0.11 mmol) in THF (1 mL) was added DIPEA (0.060 mL, 0.34 mmol), followed by propanoyl chloride (0.020 mL, 0.18 mmol). The resulting mixture was allowed to stir for 18 hours before the reaction mixture was concentrated in vacuo to afford an orange oil. The residue was dissolved in DMSO (2 mL) and purified by mass-triggered reverse phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, diluted with saturated aqueous NaHCO3 and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the title compound, Example #33-1, as a colorless solid.

Workup

  1. concentrationwas concentrated in vacuo
  2. customto afford an orange oil
  3. custompurified by mass-triggered reverse phase preparative HPLC (MeCN/water
  4. additiondiluted with saturated aqueous NaHCO3
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0466931882984dba9c29ae4e3fd53335
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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