1,2-Dichloroethane → 4-Chloro-N-[[1-(dimethylamino)cyclopentyl](phenyl)methyl]-2-methyl-6-(methylthio)benzamide

HRID 20839Notes

Reaction equation

HRID 20839 reaction equation
[NH2:1][CH:2]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3]1([N:8]([CH3:10])[CH3:9])[CH2:7][CH2:6][CH2:5][CH2:4]1.[Cl:17][C:18]1[CH:26]=[C:25]([S:27][CH3:28])[C:21]([C:22](O)=[O:23])=[C:20]([CH3:29])[CH:19]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[Cl:17][C:18]1[CH:26]=[C:25]([S:27][CH3:28])[C:21]([C:22]([NH:1][CH:2]([C:3]2([N:8]([CH3:10])[CH3:9])[CH2:7][CH2:6][CH2:5][CH2:4]2)[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:23])=[C:20]([CH3:29])[CH:19]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 11521393{1-[Amino(phenyl)methyl]cyclopentyl}dimethylamineHCID 685404964-Chloro-2-methyl-6-(methylthio)benzoic acid

Product 1

HCID 593479134-Chloro-N-[[1-(dimethylamino)cyclopentyl](phenyl)methyl]-2-methyl-6-(methylthio)benzamideYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of {1-[amino(phenyl)methyl]cyclopentyl}dimethylamine D3 enantiomer 2 (203 mg; 0.93 mmol), 4-chloro-2-methyl-6-(methylthio)benzoic acid (obtainable as described in F. P. Doyle, J. H. C. Nayler, H. R. J. Waddington, J. C. Hanson and G. R. Thomas. J. Chem. Soc. 1963, 497) (202 mg; 0.93 mmol), EDC (178 mg; 0.93 mmol) and HOBt (143 mg; 0.93 mmol) in DCM (20 ml) was stirred at room temperature for 4 h and then stood at room temperature for 90 h. The resulting reaction mixture was washed with saturated aqueous sodium bicarbonate (50 ml) and the organic layer separated by passage through a phase separation cartridge. The organic layer was evaporated, the residue dissolved in a minimum of DCM and chromatographed on silica gel, eluting with 0-100% ethyl acetate-pentane. The fractions were combined and evaporated under reduced pressure to afford the title compound (200 mg; 52%). 1H NMR (CDCl3) δ: 0.90-1.10 (1H, m), 1.38-1.55 (3H, m), 1.60-1.76 (2H, m), 1.80-1.90 (2H, m), 2.21 (6H, s), 2.26 (3H, s), 2.47 (3H, s), 5.11 (1H, d, J=6 Hz), 6.94 (1H, d, J=5.2 Hz), 7.00 (1H, m), 7.09 (1H, m), 7.20-7.35 (3H, m), 7.40-7.50 (2H, m). Mass spectrum (Electrospray LC/MS), ES+: Found 417 (MH+). C23H2935ClN2OS requires 416. Ret. time 2.03 min. The title product was converted to its corresponding hydrochloride salt (210 mg).

Workup

  1. waitstood at room temperature for 90 h
  2. customThe resulting reaction mixture
  3. washwas washed with saturated aqueous sodium bicarbonate (50 ml)
  4. customthe organic layer separated by passage through a phase separation cartridge
  5. customThe organic layer was evaporated
  6. dissolutionthe residue dissolved in a minimum of DCM
  7. customchromatographed on silica gel
  8. washeluting with 0-100% ethyl acetate-pentane
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5622664207f84f86a4a2a034450df9bf
Source dataset
uspto-grants-2010_06
Patent number
US07745642B2

Reaction notes

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