Pyridine → Ethyl 3-[bis(methylsulfonyl)amino]-6-chloro-2-(3-chlorobenzoyl)-1H-indole-1-carboxylate

HRID 651027노트

반응식

HRID 651027 반응식
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[N:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:3]=1[C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1.N1C=CC=CC=1.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>ClCCl>[CH3:32][S:33]([N:1]([S:33]([CH3:32])(=[O:35])=[O:34])[C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[N:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:3]=1[C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1)(=[O:35])=[O:34]

참가 물질

5

반응물 3

HCID 1049Pyridine2회HCID 31297Methanesulfonyl chloride2회HCID 183678683-Amino-6-chloro-2-(3-chlorobenzoyl)-1-(ethoxycarbonyl)indole

생성물 1

HCID 21710894Ethyl 3-[bis(methylsulfonyl)amino]-6-chloro-2-(3-chlorobenzoyl)-1H-indole-1-carboxylate수율 98.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of ethyl 3-amino-6-chloro-2-(3-chlorobenzoyl)-]-1H-indole-1-carboxylate (step 1 of Example 4, 507 mg, 1.25 mmol) in dichloromethane (15 ml) was added pyridine (0.32 ml, 4.04 mmol) and methanesulfonyl chloride (0.16 ml, 2.02 mmol). After stirring for 19 h, additional pyridine (1.3 ml, 16.2 mmol) and methanesulfonyl chloride (0.32 ml, 4.04 mmol) were added and the mixture heated at reflux for 17 h and then cooled to room temperature. The mixture was concentrated, and partitioned between ethyl acetate (200 ml) and 2 M aqueous HCl (100 ml). The organic layer was separated and washed with 2 M aqueous HCl (100 ml×2), saturated aqueous sodium bicarbonate (100 ml×3), and dried (Na2SO4). After removal of solvent the residue was purified by flash chromatography eluting with ethyl acetate/hexane (1:4) to afford the title compound (532 mg, 74%) as an oil.

후처리

  1. temperaturethe mixture heated
  2. temperatureat reflux for 17 h
  3. concentrationThe mixture was concentrated
  4. custompartitioned between ethyl acetate (200 ml) and 2 M aqueous HCl (100 ml)
  5. customThe organic layer was separated
  6. washwashed with 2 M aqueous HCl (100 ml×2), saturated aqueous sodium bicarbonate (100 ml×3)
  7. dry with materialdried (Na2SO4)
  8. customAfter removal of solvent the residue
  9. customwas purified by flash chromatography
  10. washeluting with ethyl acetate/hexane (1:4)

출처 및 근거

ORD 기록
ord-9f5249de2f8249f881b9dd1a8550f1b2
출처 데이터셋
uspto-grants-2001_08
특허 번호
US06277878B1

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