2,4-Dichlorobenzoyl chloride → 2,4-dichloro-N-((4-(cyclopropylmethyl)-1-(ethylsulfonyl)piperidin-4-yl)methyl)benzamide

HRID 502894Notes

Reaction equation

HRID 502894 reaction equation
[CH:1]1([CH2:4][C:5]2([CH2:16][NH2:17])[CH2:10][CH2:9][N:8]([S:11]([CH2:14][CH3:15])(=[O:13])=[O:12])[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[Cl:27][C:28]1[CH:36]=[C:35]([Cl:37])[CH:34]=[CH:33][C:29]=1[C:30](Cl)=[O:31]>C(Cl)Cl>[Cl:27][C:28]1[CH:36]=[C:35]([Cl:37])[CH:34]=[CH:33][C:29]=1[C:30]([NH:17][CH2:16][C:5]1([CH2:4][CH:1]2[CH2:2][CH2:3]2)[CH2:6][CH2:7][N:8]([S:11]([CH2:14][CH3:15])(=[O:13])=[O:12])[CH2:9][CH2:10]1)=[O:31]

Participants

5

Reactant 3

HCID 666452,4-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 686201561-[4-(Cyclopropylmethyl)-1-(ethylsulfonyl)piperidin-4-yl]methanamine

Product 1

HCID 116044492,4-dichloro-N-((4-(cyclopropylmethyl)-1-(ethylsulfonyl)piperidin-4-yl)methyl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-[4-(cyclopropylmethyl)-1-(ethylsulfonyl)piperidin-4-yl]methanamine (I-5, 250 mg, 1.0 mmol) in CH2Cl2 (10 mL) at 0° C. was treated with i-Pr2NEt (1 mL, 5.7 mmol), 2,4-dichlorobenzoyl chloride (200 μL, 1.43 mmol), and stirred for 15 min before being warmed to room temperature. After 1 h, the reaction was quenched with the addition of 1 M aqueous NaOH (10 mL) and stirred 1 h before being extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried (Na2SO4), concentrated under reduced pressure, and purified by reverse phase HPLC to afford 2,4-dichloro-N-{[4-(cyclopropylmethyl)-1-(ethylsulfonyl)piperidin-4-yl]methyl}benzamide (I-6) as an off-white amorphous solid. Analytical LCMS: single peak (214 nm), 3.328 min. 1H NMR (CDCl3, 300 MHz) δ 7.64 (d, J=8.4 Hz, 1 H), 7.46 (s, 1H), 7.35 (d, J=8.4 Hz, 1H), 6.39 (t, J=8 Hz, 1H), 3.63 (d, J=6.3 Hz, 2H), 3.41 (m, 2H), 3.35 (m, 2H), 2.98 (q, J=7.2 Hz, 1H), 1.68 (m, 5H), 1.39 (m, 5H), 0.68 (m, 1H), 0.56 (d, J=8 Hz, 1H). HRMS m/z 433.1091 (C19H26Cl2N2O3S+H+ requires 433.1091).

Workup

  1. waitAfter 1 h
  2. customthe reaction was quenched with the addition of 1 M aqueous NaOH (10 mL)
  3. stirringstirred 1 h
  4. extractionbefore being extracted with CH2Cl2 (3×20 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-680b1b52af474e2ca0e902b66c922370
Source dataset
uspto-grants-2010_08
Patent number
US07776886B2

Reaction notes

Loading…