Triethylamine → 1-Methanesulfonyl-piperidine-4-carboxylic acid [2-(2,4-dichloro-phenoxy)-phenyl]-amide

HRID 1642235Notes

Reaction equation

HRID 1642235 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].C(N(CC)CC)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>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:33]([CH3:32])(=[O:35])=[O:34])[CH2:16][CH2:15]1)=[O:13]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 57550293N-[2-(2,4-Dichlorophenoxy)phenyl]piperidine-4-carboxamide

Product 1

HCID 159530461-Methanesulfonyl-piperidine-4-carboxylic acid [2-(2,4-dichloro-phenoxy)-phenyl]-amideYield 49%

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 triethylamine (0.3 mL, 2.19 mmol) and methanesulphonyl chloride (0.034 mL, 0.438 mmol). The reaction mixture was stirred at room temperature for 24 h, and quenched 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 chromatography on silica gel using DCM to DCM/MeOH 95:5 gradient as eluent gave 1-methanesulfonyl-piperidine-4-carboxylic acid [2-(2,4-dichloro-phenoxy)-phenyl]-amide (47.6 mg, 49%) as an oil. Rf: 0.25 (hexane/EtOAc 4:6). 1H NMR (300 MHz, CDCl3) δ 1.88 (2H, m, CH2), 2.37 (1H, m, CH), 2.72 (3H, s, CH3), 2.78 (2H, m, CH2), 3.71 (2H, td, J=12.5, 3.6 Hz, CH2), 6.67 (1H, dd, J=8.1, 1.3 Hz, ArH), 6.89 (1H, d, J=8.8 Hz, ArH), 6.95 (1H, td, J=8.1, 1.6 Hz, ArH), 7.07 (1H, td, J=8.0, 1.3 Hz, ArH), 7.16 (1H, dd, J=8.8, 2.5 Hz, ArH), 7.43 (1H, d, J=2.5 Hz, ArH), 7.72 (1H, br s, NH) and 8.31 (1H, br d, J=8.1 Hz, ArH). Further purification by flash chromatography on silica gel using hexane/EtOAc 4:6 as eluent gave AMR01051 as a white solid, mp 150-151° C. LC/MS (APCI) tr=4.63 min, m/z 443.37 (M++H, 100), 445.39 (55). HPLC tr=2.52 min (100%)

Workup

  1. customquenched with saturated NaHCO3
  2. extractionThe resulting solution was extracted with DCM (3×20 mL)
  3. washthe combined organic layers were washed with water, 1M HCl (3×20 mL) and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-bde66764945748e08e3283e20817487a
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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