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

HRID 1876759Notes

Reaction equation

HRID 1876759 reaction equation
[O-]CC.[Na+].Cl.[CH3:6][N:7]1[CH2:12][CH2:11][CH:10]([CH2:13][CH2:14][CH2:15][NH:16][C:17]([NH2:19])=[NH:18])[CH2:9][CH2:8]1.[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:19]=[C:17]([NH:16][CH2:15][CH2:14][CH2:13][CH:10]2[CH2:9][CH2:8][N:7]([CH3:6])[CH2:12][CH2:11]2)[N:18]=1

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 534170282-(Ethoxymethylidene)-3-oxobutanenitrileHCID 178480301HCID 178480301, 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-ea7894852baf497da35542dd662bb26f
Source dataset
uspto-grants-2012_11
Patent number
US08309720B2

Reaction notes

Loading…