4-Methoxybenzenesulfonyl chloride → N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-4-(methyloxy)benzenesulfonamide

HRID 1874988Notes

Reaction equation

HRID 1874988 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([Cl:19])=[C:7]([O:9][C:10]2[CH:11]=[C:12]([CH:15]=[C:16]([Cl:18])[CH:17]=2)[C:13]#[N:14])[CH:8]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:19][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:1][S:28]([C:25]2[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=2)(=[O:30])=[O:29])=[CH:8][C:7]=1[O:9][C:10]1[CH:11]=[C:12]([C:13]#[N:14])[CH:15]=[C:16]([Cl:18])[CH:17]=1

Participants

5

Reactant 3

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 594514053-{[5-(Aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 59451394N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-4-(methyloxy)benzenesulfonamideYield 76.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-{[5-(aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile (0.025 g, 0.085 mmol), 4-(methyloxy)benzenesulfonyl chloride, (0.025 g, 0.13 mmol) and DIPEA (0.05 mL, 0.25 mmol) in CH2Cl2 (2 mL) was stirred overnight. The solvent was concentrated and purification was accomplished by RP-HPLC (water/acetonitrile/0.1% TFA). The desired fractions were lyophilized and EtOAc (25 mL) and sat. NaHCO3 (10 mL) were added. The layers were separated and the aqueous layer extracted with EtOAc (2×10 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated to afford N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-4-(methyloxy)benzenesulfonamide (0.030 g, 75%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 8.03 (t, 1H), 7.80 (d, 1H), 7.66 (d, 2H), 7.51 (d, 1H), 7.38 (dd, 1H), 7.32 (t, 1H), 7.15 (dd, 1H), 6.99-7.10 (m, 3H), 3.96 (d, 2H), 3.78 (s, 3H). MS: m/z 485 (M+23).

Workup

  1. concentrationThe solvent was concentrated
  2. custompurification
  3. additionEtOAc (25 mL) and sat. NaHCO3 (10 mL) were added
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with EtOAc (2×10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f4bd17b6c9b3451abdff59248837ede5
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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