Acetic Acid → HCID 86729398, compound

HRID 521229Notes

Reaction equation

HRID 521229 reaction equation
[C:1]([CH2:3][C:4]1([N:10]2[CH:14]=[C:13]([C:15]([NH2:17])=[O:16])[C:12]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[N:11]2)[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)#[N:2].[C:26]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)(=O)[CH3:27].C(O)(=O)C.C([BH3-])#N.[Na+]>CO.CN(C=O)C>[C:1]([CH2:3][C:4]1([N:10]2[CH:14]=[C:13]([C:15]([NH2:17])=[O:16])[C:12]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)=[N:11]2)[CH2:9][CH2:8][N:7]([CH:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH3:27])[CH2:6][CH2:5]1)#[N:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 7410AcetophenoneHCID 5003444Sodium cyanoborohydrideHCID 86729399HCID 86729399, compound2×

Product 1

HCID 86729398HCID 86729398, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-(cyanomethyl)piperidin-4-yl)-3-((4-fluorophenyl)amino)-1H-pyrazole-4-carboxamide (Intermediate #38-5) (50 mg, 0.11 mmol) in MeOH (0.32 mL) and DMF (0.063 mL) was added acetophenone (41 mg, 0.34 mmol) and acetic acid (0.065 mL, 1.1 mmol). The reaction mixture was allowed to stir at room temperature for 15 minutes. Sodium cyanoborohydride (7 mg, 0.1 mmol) was added and the reaction mixture was allowed to stir for 24 hours at ambient temperature. The mixture was then purified directly by mass-triggered reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and concentrated in vacuo. The residue was dissolved in MeOH and passed through a Si-Carbonate cartridge to afford the title compound as a free base.

Workup

  1. stirringto stir for 24 hours at ambient temperature
  2. customThe mixture was then purified directly by mass-triggered reverse-phase preparative HPLC (MeCN/water
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in MeOH

Sources & evidence

ORD record
ord-e0be047da1e5459796cd2224ddf10a50
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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