4-Chloro-3-(2-dimethylamino-ethoxy)aniline → 4,5-Dimethoxy-biphenyl-2-sulfonic acid [4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-amide

HRID 22764Notes

Reaction equation

HRID 22764 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[S:12]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH2:24][CH2:25][N:26]([CH3:28])[CH3:27])[CH:17]=1)(=[O:14])=[O:13].CN(CCO[C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][C:41]=1Cl)N)C.BrC1C(OC)=C(OC)C=CC=1S(Cl)(=O)=O>ClC(Cl)C>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][S:12]([C:3]2[C:2]([C:35]3[CH:36]=[CH:37][CH:39]=[CH:40][CH:41]=3)=[CH:7][C:6]([O:8][CH3:9])=[C:5]([O:10][CH3:11])[CH:4]=2)(=[O:14])=[O:13])=[CH:17][C:18]=1[O:23][CH2:24][CH2:25][N:26]([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 121354204-Chloro-3-(2-dimethylamino-ethoxy)anilineHCID 121354212-Bromo-N-[4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-4,5-dimethoxy-benzenesulfonamideHCID 22591670HCID 22591670, compound

Product 1

HCID 101172974,5-Dimethoxy-biphenyl-2-sulfonic acid [4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-amideYield 72%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

2-Bromo-4,5-dimethoxybenzenesulfonyl chloride To a cooled (0° C.) solution of 4-bromoveratrole (15 mL, 100 mmol) in dichloromethane (100 mL) was added dropwise chlorosufonic acid (26 mL, 400 mmol). The reaction was allowed to slowly warm to ambient temperature and maintained for 3 hours, at which time it was concentrated and diluted with ether (300 mL). The resultant solution was then washed with ice cold water (2×250 mL) and brine (100 mL), dried over magnesium sulfate, and concentrated to furnish a grayish powder (25 g, 78%). b) 2-Bromo-N-[4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-4,5-dimethoxy-benzenesulfonamide To a solution of 3-[2-(N,N-dimethylamino)ethoxy]-4-chloroaniline (1.9 g, 8.8 mmol) in dichloroethane (50 mL) was added 2-bromo-3,4-dimethoxybenzenesulfonyl chloride (2.8 g, 8.8 mmol). The resultant solution was maintained at ambient temperature for 3 days, then concentrated. Crystallization from ethanol gave the title compound (3.4 g, 72%). MS (ES+) m/e 493 [M+H]+ c) 4,5-Dimethoxy-biphenyl-2-sulfonic acid [4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-amide To a solution of 2-bromo-N-[4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-4,5-dimethoxy-benzenesulfonamide (50 mg, 0.1 mmol) in dimethoxyethane/water (25:3, 2 mL) was added phenylboronic acid (120 mg, 1.0 mmol), cesium carbonate (820 mg, 2.5 mmol), and tetrakispalladium triphenylphosphine (6 mg, 0.005 mmol). The resultant mixture was heated at 90° C. for 16 hours, at which time it was diluted with ethyl acetate (10 mL) and washed with 5% sodium hydroxide (2×10 mL) and brine (10 mL). The solution was then dried over magnesium sulfate and concentrated to give a yellow oil. Purification by HPLC (gradient; 10% acetonitrile/water to 90% acetonitrile/water) furnished the title compound (15 mg, 31%) as a white solid. MS (ES+) m/e 491 [M+H]+ Example 20 was prepared as outlined in Example 19, substituting the appropriate starting materials.

Workup

  1. concentrationconcentrated
  2. customCrystallization from ethanol

Sources & evidence

ORD record
ord-5ab06c79050d4bfcb332c54e999c09bb
Source dataset
uspto-grants-2005_02
Patent number
US06849635B2

Reaction notes

Loading…