Trifluoroacetic acid → 1-[1-(Biphenyl-4-ylmethyl)-4-(cyanomethyl)piperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide

HRID 521227Notes

Reaction equation

HRID 521227 reaction equation
[C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][C:4]([CH:7]=O)=[CH:3][CH:2]=1.FC(F)(F)C([O-])=O.[C:22]([C:25]1[C:26]([NH:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[N:27][N:28]([C:30]2([CH2:36][C:37]#[N:38])[CH2:35][CH2:34][NH2+:33][CH2:32][CH2:31]2)[CH:29]=1)(=[O:24])[NH2:23].C(O)(C(F)(F)F)=O>CN(C=O)C>[C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:33]2[CH2:34][CH2:35][C:30]([N:28]3[CH:29]=[C:25]([C:22]([NH2:23])=[O:24])[C:26]([NH:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[N:27]3)([CH2:36][C:37]#[N:38])[CH2:31][CH2:32]2)=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 76689(1,1'-Biphenyl)-4-carboxaldehydeHCID 867293834-[4-Carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidinium trifluoroacetate

Product 1

HCID 867293941-[1-(Biphenyl-4-ylmethyl)-4-(cyanomethyl)piperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Biphenyl-4-carbaldehyde (12 mg, 0.070 mmol) was treated with a solution of 4-[4-carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-2) (20 mg, 0.050 mmol) and TFA (0.020 mL, 0.23 mmol) in DMF (0.65 mL). The resulting solution was then treated with MP-(OAc)3BH (80 mg, 0.16 mmol). The resulting mixture was shaken at ambient temperature for 16 hours on an orbital shaker. The mixture was then filtered through a 0.45 micron fit and the fit was washed with DMSO (1.0 mL). The filtrate was then purified directly by reverse-phase preparative HPLC (using a gradient elution of 5-95% MeCN/water, with 0.1% v/v NH4OH modifier). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound, Example #21-1.

Workup

  1. filtrationThe mixture was then filtered through a 0.45 micron fit
  2. washthe fit was washed with DMSO (1.0 mL)
  3. customThe filtrate was then purified directly by reverse-phase preparative HPLC (
  4. washa gradient elution of 5-95% MeCN/water
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc3b3be777c1421cbe5c052ed9161bef
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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