Reaction #487578

Reaction equation

carbonyldiimidazole

4-(2-aminoethyl)morpholine

3-(4-aminopiperidin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)-benzonitrile

→

isopropyl ether

1-(1-(5-cyano-2-(3,5-dichlorophenoxy)phenylsulfonyl)-piperidin-4-yl)-3-(2-morpholinoethyl)urea

1-(1-(5-cyano-2-(3,5-dichlorophenoxy)phenylsulfonyl)piperidin-4-yl)-3-(2-morpholinoethyl)urea

Solvents

THF

dichlormethane

Conditions

Workup

1. 1
   Otherwas consumed (confirmed by HPLC)
2. 2
   workup.STIRRINGthe mixture was stirred 19 hours
3. 3
   ConcentrationConcentration in vacuo
4. 4
   Otherprovided a white solid, which
5. 5
   Otherpartitioned with water
6. 6
   Extractionthe aqueous layer extracted three times with dichloromethane
7. 7
   WashThe combined organic layers were washed with brine
8. 8
   Dryingdried over anhydrous magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated in vacuo
11. 11
    Otherto yield a white solid

Procedure

1-(1-(5-cyano-2-(3,5-dichlorophenoxy)phenylsulfonyl)-piperidin-4-yl)-3-(2-morpholinoethyl)urea (22) is prepared according to the following method as an alternative to the method of Example 32. 3-(4-aminopiperidin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)-benzonitrile (1.002 g), prepared according to Example 1, and carbonyldiimidazole (420 mg, 1.1 eq.) were combined in THF (15 mL) and stirred at room temperature. After 5 hours, starting material was consumed (confirmed by HPLC). 4-(2-aminoethyl)morpholine (512 mg, 2.0 eq.) was added and the mixture was stirred 19 hours. Concentration in vacuo provided a white solid, which was resuspended in dichlormethane, partitioned with water, and the aqueous layer extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield a white solid. Trituration with isopropyl ether yielded a 96% pure product according to HPLC. The powder was suspended in minimal amounts of hot methanol, stirred at 60° C. for 30 minutes, cooled in an ice bath and vacuum filtered to obtain the product as a white powder (831 mg, 60.7% yield, 98% purity).

Source