Pyridine → 1-(2,5-Dichlorobenzenesulfonyl)piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)-phenyl]amide

HRID 1642236Notes

Reaction equation

HRID 1642236 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[O:13].N1C=CC=CC=1.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=1[S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([CH:14]1[CH2:19][CH2:18][N:17]([S:39]([C:33]2[CH:34]=[C:35]([Cl:38])[CH:36]=[CH:37][C:32]=2[Cl:31])(=[O:41])=[O:40])[CH2:16][CH2:15]1)=[O:13]

Participants

5

Reactant 3

HCID 1049PyridineHCID 794012,5-Dichlorobenzenesulfonyl chlorideHCID 57550293N-[2-(2,4-Dichlorophenoxy)phenyl]piperidine-4-carboxamide

Product 1

HCID 159516861-(2,5-Dichlorobenzenesulfonyl)piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)-phenyl]amideYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)-phenyl]amide (AMR01038, 80 mg, 0.219 mmol) in dry DCM (6 mL) were added pyridine (0.035 mL, 0.438 mmol) and 2,5-dichlorobenzenesulphonyl chloride (59.2 mg, 0.241 mmol). The reaction mixture was stirred at room temperature for 24 h, and then at reflux for 3 h. After quenching with saturated NaHCO3, the resulting solution was extracted with DCM (3×20 mL), and the combined organic layers were washed with water, 1M HCl (3×20 mL) and brine, dried (MgSO4), filtered and evaporated. Flash column chromatography on silica gel using hexane/EtOAc 8:2 as eluent gave 1-(2,5-dichlorobenzenesulfonyl)piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)-phenyl]amide (56 mg, 44%) as a white solid, mp 194-196° C. Rf: 0.81 (DCM/MeOH 9:1). 1H NMR (300 MHz, CDCl3) δ 1.74-1.96 (4H, m, 2CH2), 2.34 (1H, m, CH), 3.80 (2H, td, J=13.1, 3.4 Hz, CH2), 6.65 (1H, dd, J=8.1, 1.4 Hz, ArH), 6.87 (1H, d, J=8.8 Hz, ArH), 6.94 (1H, td, J=7.7, 1.7 Hz, ArH), 7.05 (1H, td, J=8.0, 1.4 Hz, ArH), 7.15 (1H, dd, J=8.8, 2.5 Hz, ArH), 7.37 (2H, d, J=1.4 Hz, ArH), 7.41 (1H, d, J=2.5 Hz, ArH), 7.68 (1H, br s, NH), 7.97 (1H, t, J=1.4 Hz, ArH) and 8.29 (1H, dd, J=8.0, 1.0 Hz, ArH). LC/MS (APCI) tr=5.62 min, m/z 577.21 (59), 575.26 (100), 573.24 (M++H, 90) HPLC tr=3.363 min (97.70%)

Workup

  1. temperatureat reflux for 3 h
  2. customAfter quenching with saturated NaHCO3
  3. extractionthe resulting solution was extracted with DCM (3×20 mL)
  4. washthe combined organic layers were washed with water, 1M HCl (3×20 mL) and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-35f4d2984f184b9792b5af37b2181830
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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