Reaction #487575

Reaction equation

3-fluorophenyl isocyanate

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

triethyl amine

→

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

desired product

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

Solvents

methylene chloride

Conditions

Workup

1. 1
   Otherthe starting material was consumed
2. 2
   workup.ADDITION4 mL of hexanes was added
3. 3
   Filtrationthe product collected by vacuum filtration
4. 4
   Washwashed with 1N HCl

Procedure

3-(4-aminopiperidin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)benzonitrile was prepared following the procedure of Example 1. The final product was prepared by the addition of triethyl amine (0.42 mL) followed by 3-fluorophenyl isocyanate to a solution of 3-(4-aminopiperidin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)benzonitrile (102 mg) in methylene chloride (4.0 mL). After stirring for 3 hours, the starting material was consumed, as confirmed by TLC (50% EtOAc/hexanes). 4 mL of hexanes was added and the product collected by vacuum filtration and washed with 1N HCl. The desired product was obtained as a white powder (99 mg, 73.3%). 1H NMR (500 MHz, DMSO-d6) δ: 8.61 (s, 1H), 8.28 (d, J=2 Hz, 1H), 8.13 (dd, J1=9 Hz, J2=2 Hz, 1H), 7.55 (t, J=2 Hz, 2H), 7.42 (m, 1H), 7.37 (d, J=2 Hz, 2H), 7.34 (d, J=9 Hz, 1H), 7.22 (m, 1H), 6.99 (m, 1H), 6.68 (m, 1H), 6.33 (d, J=8 Hz, 1H), 3.61 (m, 3H), 2.96 (m, 2H), 1.88 (m, 2H), 1.40 (m, 2H). MS (ESI+ ion, m/z): 564.

Source