Pyridine → Rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-urea

HRID 397196노트

반응식

HRID 397196 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([O:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.ClCCl.[CH3:31][NH:32][C:33]([NH2:35])=[O:34].N1C=CC=CC=1>FC1C=CC=CC=1.CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([O:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:35][C:33]([NH:32][CH3:31])=[O:34])=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

참가 물질

9

반응물 5

HCID 1049PyridineHCID 6344DichloromethaneHCID 11719MethylureaHCID 65578Oxalyl chlorideHCID 18172604Rac-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetic acid

생성물 1

HCID 10200321Rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-urea수율 67%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 10008Fluorobenzene용매

반응 조건

온도
25 °C

실험 절차

A cooled (0° C.) solution of rac-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetic acid (Example 6; 100 mg, 0.30 mmol) in fluorobenzene (2.5 mL) and N,N-dimethylformamide (1.8 μL). was treated with a 2.0 M solution of oxalyl chloride in dichloromethane (0.18 mL, 0.36 mmol). Immediately a vigorous gas evolution was observed, and the mixture was stirred at 25° C. for 1 h and became light yellow in color. Methyl urea (97 mg, 0.90 mmol) was then added and after the reaction was heated at 70° C. for 10 min, pyridine (0.048 mL, 0.60 mmol) was added and the reaction was maintained at 70° C. for 1 h. The cooled mixture was diluted with ethyl acetate (5 mL) then was filtered through Celite to remove insoluble materials and the filtrate concentrated in vacuo. The concentrate was washed with 3N hydrochloric acid (1×20 mL), saturated sodium bicarbonate (1×15 mL) and brine (1×15 mL), then was dried over sodium sulfate, filtered and evaporated under reduced pressure. The product was purified by chromatography (Biotage Flash 40S column, 50/50 hexanes/ethyl acetate) to provide rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-urea (78 mg, 67% yield) as a white foam: FAB-HRMS m/e calculated for C16H21N2O5SCl (M+H)+ 389.0938, found 389.0943.

후처리

  1. temperatureafter the reaction was heated at 70° C. for 10 min
  2. temperaturethe reaction was maintained at 70° C. for 1 h
  3. filtrationthen was filtered through Celite
  4. customto remove insoluble materials
  5. concentrationthe filtrate concentrated in vacuo
  6. washThe concentrate was washed with 3N hydrochloric acid (1×20 mL), saturated sodium bicarbonate (1×15 mL) and brine (1×15 mL)
  7. dry with materialwas dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe product was purified by chromatography (Biotage Flash 40S column, 50/50 hexanes/ethyl acetate)

출처 및 근거

ORD 기록
ord-6656c40ae0bc47fc9cc442e755907f4b
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06608218B2

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