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

HRID 20839ノート

反応式

HRID 20839 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-5622664207f84f86a4a2a034450df9bf
出典データセット
uspto-grants-2010_06
特許番号
US07745642B2

反応ノート

読み込み中…