Triethylamine → HCID 15951685, compound

HRID 1642261Notes

Reaction equation

HRID 1642261 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:19]=[CH:18][CH:17]=[CH:16][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)=[O:8].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:19]=[CH:18][CH:17]=[CH:16][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][N:13]([S:33]([CH3:32])(=[O:35])=[O:34])[CH2:12][CH2:11]1)=[O:8]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 575503182-(2,4-Dichlorophenoxy)-N-(piperidin-4-yl)benzamide

Product 1

HCID 15951685HCID 15951685, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of 4-[2-(2,4-dichlorophenoxy)-N-piperidin-4-ylbenzamide (AMR01077, 100 mg, 0.274 mmol) in dry DCM (5 mL) were added triethylamine (0.2 mL, 1.37 mmol) and methanesulphonyl chloride (0.125 mL, 1.6 mmol). The reaction mixture was stirred overnight at room temperature, and quenched with saturated NaHCO3. The resulting solution was extracted with DCM (3×20 mL), and the combined organic layers were washed with water and dried (MgSO4). The dessicant was filtered off and the resulting solution was treated with trisamine scavenger (100 mg) for 2 h. The scavenger was filtered off, and the solvent evaporated to dryness. Column chromatography of the crude product using DCM/MeOH 95:5 as eluent gave 2-(2,4-Dichloro-phenoxy)-N-(1-methanesulfonyl-piperidin-4-yl)-benzamide (86 mg, 72%) as a white solid. LC/MS (APCI) tr=4.56 min, m/z 445.32 (65), 443.31 (M++H, 100). HPLC tr=3.42 min (97.52%) 1H NMR (270 MHz, CDCl3) 1.56-1.69 (2H, m, CH2), 2.06 (2H, m, CH2), 2.75 (3H, s, CH3), 2.86 (2H, m, CH2), 3.68 (2H, m, CH2), 4.09 (1H, m, CH), 6.79 (1H, dd, J=8.2, 1.0 Hz, ArH), 6.88 (1H, d, J=8.9 Hz, ArH), 7.20-7.28 (2H, m, ArH), 7.38-7.42 (2H, m, ArH+NH), 7.51 (1H, d, J=2.5 Hz, ArH) and 8.15 (1H, dd, J=7.9, 2.0 Hz, ArH). 13C NMR (270 MHz, CDCl3) δ 31.47 (CH2), 34.83 (CH3), 44.96 (CH2), 46.28 (CH), 117.76, 120.77, 124.32, 124.83, 125.88, 128.59, 130.44, 130.88, 132.56, 133.04, 149.79, 153.56 (ArC), and 163.97 (C═O).

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
  4. dry with materialdried (MgSO4)
  5. filtrationThe dessicant was filtered off
  6. additionthe resulting solution was treated with trisamine scavenger (100 mg) for 2 h
  7. filtrationThe scavenger was filtered off
  8. customthe solvent evaporated to dryness

Sources & evidence

ORD record
ord-b63d9f76ae8d4d849fac57d65022e144
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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