Pyridine → 1-Benzoyl-N-[2-(4-chlorophenoxy)phenyl]piperidine-4-carboxamide

HRID 1642230노트

반응식

HRID 1642230 반응식
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][C:14]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[O:15])=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:30](Cl)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][C:14]([CH:16]2[CH2:17][CH2:18][N:19]([C:30](=[O:37])[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:20][CH2:21]2)=[O:15])=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 1049PyridineHCID 7412Benzoyl chlorideHCID 57550281N-[2-(4-Chlorophenoxy)phenyl]piperidine-4-carboxamide

생성물 1

HCID 159529411-Benzoyl-N-[2-(4-chlorophenoxy)phenyl]piperidine-4-carboxamide수율 83.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To an ice cooled solution of piperidine-4-carboxylic acid [2-(4-chlorophenoxy)phenyl]amide (AMR01033, 73 mg, 0.22 mmol) in dry DCM (6 mL) were added pyridine (0.036 mL, 0.44 mmol) and benzoyl chloride (0.038 mL, 0.33 mmol). The reaction mixture was stirred at room temperature until TLC showed consumption of starting material (1 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 of the crude product using hexane to EtOAc gradient as eluent gave 1-benzoylpiperidine-4-carboxylic acid [2-(4-chlorophenoxy)phenyl]amide (80 mg, 83%) as a white solid, mp 158-160° C. Rf: 0.48 (EtOAc) LC/MS (APCI) tr=1.05 min, m/z 437.33 (45), 435.38 (M++H, 100) HPLC tr=2.551 min (98.36%) 1H NMR (270 MHz, CDCl3) δ 1.82 (4H, m, 2CH2), 2.51 (1H, tt, CH), 2.98 (2H, n, CH2), 3.85 (1H, m, ½CH2), 4.71 (1H, m, ½CH2), 6.82 (1H, dd, J=8.2, 1.5 Hz, ArH), 6.93 (2H, AA′BB′, ArH), 7.02 (1H, td, ArH), 7.13 (1H, td, ArH), 7.31 (1H, AA′BB′, ArH), 7.39 (5H, s, ArH,), 7.70 (1H, br s, NH) and 8.39 (1H, dd, J=8.2, 1.5 Hz, ArH). Anal. Calcd. for C25H23ClN2O3: C, 69.04; H, 5.33; N, 6.44. Found: C, 68.9; H, 5.33; N, 6.37%.

후처리

  1. customconsumption of starting material (1 h)
  2. customquenched 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

출처 및 근거

ORD 기록
ord-b06dd98f88d3479389bb333d603b8b3b
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08119627B2

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