Methyl cyanoacetate → 1-[1-(Cyanoacetyl)-4-(cyanomethyl)piperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide
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].C1CCN2C(=NCCC2)CC1.[C:43]([CH2:45][C:46](OC)=[O:47])#[N:44].C([O-])(O)=O.[Na+]>>[C:43]([CH2:45][C:46]([N:19]1[CH2:20][CH2:21][C:16]([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)([CH2:22][C:23]#[N:24])[CH2:17][CH2:18]1)=[O:47])#[N:44]Participants
5
Reactant 4
Product 1
Procedure
To a suspension of 4-[4-carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl) piperidinium trifluoroacetate (60 mg, 0.14 mmol) in Me-THF (2.0 mL) was added DBU (0.065 mL, 0.43 mmol), followed by methyl cyanoacetate (28 mg, 0.29 mmol). The resulting mixture was allowed to stir for 1 hour before saturated aqueous NaHCO3 solution was added and the resulting mixture was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 50-100%, EtOAc/hexanes followed by elution with 10% MeOH/EtOAc) to afford the title compound, Example #36-1.
Workup
- additionwas added
- extractionthe resulting mixture was extracted with EtOAc (3×)
- dry with materialThe combined organic layers were dried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by MPLC on silica gel (
- washa gradient elution of 50-100%, EtOAc/hexanes
- washfollowed by elution with 10% MeOH/EtOAc)
Sources & evidence
- ORD record
- ord-7def7192c58d4dde8b4c6b3f320d8dbb
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328099B2
Reaction notes
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