(4-fluorophenyl)methanesulfonyl Chloride → N-[5-(3-chloro-4-cyano-phenyl)-pyridin-3-yl]-1-(4-fluoro-phenyl)-methanesulfonamide

HRID 1897762Notes

Reaction equation

HRID 1897762 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([Cl:16])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][S:25](Cl)(=[O:27])=[O:26])=[CH:20][CH:19]=1>N1C=CC=CC=1>[Cl:16][C:10]1[CH:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][S:25]([CH2:24][C:21]3[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=3)(=[O:26])=[O:27])[CH:7]=[N:6][CH:5]=2)[CH:15]=[CH:14][C:11]=1[C:12]#[N:13]

Participants

4

Reactant 2

HCID 2759108(4-fluorophenyl)methanesulfonyl ChlorideHCID 595783904-(5-Amino-pyridin-3-yl)-2-chloro-benzonitrile

Product 1

HCID 49819668N-[5-(3-chloro-4-cyano-phenyl)-pyridin-3-yl]-1-(4-fluoro-phenyl)-methanesulfonamideYield 23.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

According to General Sulfonylation Procedure 2 in Example 1, to a solution of 4-(5-amino-pyridin-3-yl)-2-chloro-benzonitrile (20 mg, 87 μmol, 1 eq) in anhydrous pyridine (500 μl) was added (4-fluoro-phenyl)-methanesulfonyl chloride (20 mg, 96 μmol, 1.1 eq). The crude product was purified by Isco Cornbiflash® Companion™ flash chromatography system on normal phase (4 g SiO2, flow rate 18 mL/min), eluting with mixtures of dichloromethane/methanol, to give N-[5-(3-chloro-4-cyano-phenyl)-pyridin-3-yl]-1-(4-fluoro-phenyl)-methanesulfonamide (8.2 mg, >95% purity, yield: 23.4%). The isolated product was lyophilized and identified by LC-MS (system 1) and NMR (system 2): ESI-MS m/z: 402 [M+H]+, retention time=2.24 min, 1H NMR (400 MHz, DMSO-d6) δ ppm 4.67 (s, 2H) 7.09-7.16 (m, 2H) 7.29-7.37 (m, 2H) 7.66 (t, J=2.27 Hz, 1H) 7.78 (dd, J=8.15, 1.71 Hz, 1H) 8.02 (d, J=1.64 Hz, 1H) 8.09 (d, J=8.08 Hz, 1H) 8.34 (d, J=2.40 Hz, 1H) 8.61 (d, J=2.02 Hz, 1H) 10.24 (br. s., 1H).

Workup

  1. customThe crude product was purified by Isco Cornbiflash® Companion™ flash chromatography system on normal phase (4 g SiO2, flow rate 18 mL/min)
  2. washeluting with mixtures of dichloromethane/methanol

Sources & evidence

ORD record
ord-dc445ff8d22a4a8e897f17012f70695c
Source dataset
uspto-grants-2013_08
Patent number
US08519142B2

Reaction notes

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