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

HRID 20838노트

반응식

HRID 20838 반응식
[CH3:1][C:2]([N:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:11])[CH:3]([NH2:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=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.O.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>C(Cl)Cl>[Cl:17][C:18]1[CH:26]=[C:25]([S:27][CH3:28])[C:21]([C:22]([NH:10][CH:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:2]([CH3:1])([N:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[CH3:11])=[O:23])=[C:20]([CH3:29])[CH:19]=1

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 27960291-Hydroxybenzotriazole hydrateHCID 25158607[2-Methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]amineHCID 685404964-Chloro-2-methyl-6-(methylthio)benzoic acid

생성물 1

HCID 593478944-Chloro-2-methyl-N-[2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]-6-(methylthio)benzamide수율 66.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of (+)-[2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]amine D6 (262 mg; 1.2 mmol), 4-chloro-2-methyl-6-(methylthio)benzoic acid (388 mg; 1.8 mmol), 1-hydroxybenzotriazole hydrate (276 mg; 1.8 mmol) and EDC (345 mg; 1.8 mmol) in DCM (16 ml) was stirred for 16 h. The reaction mixture was then partitioned between DCM and saturated aqueous sodium hydrogen carbonate and the organic layer separated, washed with brine, dried and evaporated. The residue was chromatographed on silica gel eluting with an ethyl acetate-hexane 0 to 100% gradient to give the title compound as a colourless oil (332 mg; 66%). 1H NMR (CDCl3) δ: 0.90 (3H, s), 0.98 (3H, s), 1.66-1.75 (4H, m), 2.31 (3H, s), 2.44 (3H, s), 2.60-2.65 (2H, m), 2.69-2.74 (2H, m), 4.82 (1H, d J=3 Hz), 7.00 (1H, m), 7.09 (1H, m), 7.11 (1H, br s), 7.23-7.33 (3H, m), 7.41-7.43 (2H, m). Mass Spectrum (Electrospray LC/MS): Found 417 (MH+). C23H2935ClN2OS requires 416. Ret. time 2.08 min. The product was dissolved in methanol and 1M HCl/diethylether solution was added dropwise to the stirred solution. After stirring at room temperature for 5 minutes, the mixture was evaporated at reduced pressure. It was redissolved in DCM and evaporated again at reduced pressure to yield the hydrochloride salt as a white foam (320 mg).

후처리

  1. customThe reaction mixture was then partitioned between DCM and saturated aqueous sodium hydrogen carbonate
  2. customthe organic layer separated
  3. washwashed with brine
  4. customdried
  5. customevaporated
  6. customThe residue was chromatographed on silica gel eluting with an ethyl acetate-hexane 0 to 100% gradient

출처 및 근거

ORD 기록
ord-52225a70b5854f56ba6809b95ca1d2de
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745642B2

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