Hydrochloric Acid → 4-Methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbonitrile

HRID 2199564Notes

Reaction equation

HRID 2199564 reaction equation
[O-]CC.[Na+].[CH3:5][N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][CH2:13][CH2:14][NH:15][C:16]([NH2:18])=[NH:17])[CH2:8][CH2:7]1.Cl.[C:20]([C:23](=[CH:26]OCC)[C:24]#[N:25])(=O)[CH3:21]>C(O)C>[CH3:21][C:20]1[C:23]([C:24]#[N:25])=[CH:26][N:18]=[C:16]([NH:15][CH2:14][CH2:13][CH2:12][CH:9]2[CH2:8][CH2:7][N:6]([CH3:5])[CH2:11][CH2:10]2)[N:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 534170282-(Ethoxymethylidene)-3-oxobutanenitrileHCID 178480300HCID 178480300, compound

Product 1

HCID 445457774-Methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A flask containing sodium ethoxide (0.64 mL of a 21 wt % solution in ethanol, 1.7 mmol) and N-[3-(1-methyl-piperidin-4-yl)-propyl]-guanidine.HCl (200 mg, 0.85 mmol) in ethanol (2.45 mL) was aged for 15 minutes at room temperature. To the resultant mixture was then added 2-acetyl-3-ethoxy-acrylonitrile (148 mg, 1.06 mmol). The resultant mixture was warmed to 80° C. for 5 h, then cooled to room temperature and concentrated. The resultant residue was partitioned between 1 N NaOH and dichloromethane. After separation of the layers, the aqueous layer was extracted with additional dichloromethane (2×). The combined organic layers were dried over MgSO4, filtered, and concentrated to yield the title compound as a solid.

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was partitioned between 1 N NaOH and dichloromethane
  3. customAfter separation of the layers
  4. extractionthe aqueous layer was extracted with additional dichloromethane (2×)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1b355abb48634878a95549513f097d3b
Source dataset
uspto-grants-2016_06
Patent number
US09359327B2

Reaction notes

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