Iodine → 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

HRID 655759노트

반응식

HRID 655759 반응식
[Cl:1][C:2]1[C:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14](C(OCC)=O)[CH2:13][C@@H:12]2[O:22][CH2:23][CH:24]=[CH2:25])=[O:9])[NH:5][C:6]=1[CH3:7].II.C[Si](C)(C)[Si](C)(C)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]2[O:22][CH2:23][CH:24]=[CH2:25])=[O:9])[NH:5][C:6]=1[CH3:7]

참가 물질

6

반응물 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 74057HexamethyldisilaneHCID 59402444Ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate2회

생성물 1

HCID 594025964-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide수율 33.3%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

To as solution of ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate (Intermediate 21, 1.1 g, 2.79 mmol) in toluene (190 mL) was added iodine (2.9 g, 11.16 mmol) followed by hexamethyldisilane (4.65 mL, 22.33 mmol). The reaction mixture was heated to reflux for 30 h and then cooled to room temperature. The reaction mixture was treated 10% sodium thiosulphate (150 mL) and the layers were separated. The aqueous layer was extracted with toluene and the organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification by column chromatography (silica, 4% methanol in dichloromethane) afforded 300 mg (33%) of 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 30 h
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with toluene
  5. dry with materialthe organic layer was dried over anhydrous sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (silica, 4% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-51c0382585ff426ead7be86c68e881f1
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071605B2

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