Methanol → 4-Chloro-6-methyl-10,10-dioxo-2-[4-(2-piperazin-1-yl-ethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1172517노트

반응식

HRID 1172517 반응식
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.Cl[CH2:11][CH2:12][N:13]([CH2:36][CH2:37]Cl)[C:14]1[CH:34]=[C:33]([Cl:35])[C:17]2[O:18][C:19]3[C:28]([CH3:29])=[CH:27][C:26]([C:30]([OH:32])=[O:31])=[CH:25][C:20]=3[S:21](=[O:24])(=[O:23])[CH2:22][C:16]=2[CH:15]=1.[CH3:39]O>>[CH3:39][O:32][C:30]([C:26]1[CH:27]=[C:28]([CH3:29])[C:19]2[O:18][C:17]3[C:33]([Cl:35])=[CH:34][C:14]([N:13]4[CH2:12][CH2:11][N:1]([CH2:2][CH2:3][N:4]5[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]5)[CH2:37][CH2:36]4)=[CH:15][C:16]=3[CH2:22][S:21](=[O:23])(=[O:24])[C:20]=2[CH:25]=1)=[O:31]

참가 물질

4

반응물 3

HCID 887MethanolHCID 8795AminoethylpiperazineHCID 1317284742-[Bis-(2-chloroethyl)amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid

생성물 1

HCID 1317284874-Chloro-6-methyl-10,10-dioxo-2-[4-(2-piperazin-1-yl-ethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

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온도
70 °C

실험 절차

N-Aminoethyl piperazine (0.6 mL, 5.2 mmol) was added to a solution of Example 102j (0.5 g, 1.04 mmol) in methanol (5 mL), followed by the addition of n-tetrabutylammonium iodide (0.075 g, 0.20 mmol) in an atmosphere of nitrogen, in a pressure reactor vessel at 120° C. for 5 h. The reaction mixture was brought to room temperature, concentrated and treated with water. The solid that separated was washed with water, dried, treated with methanolic HCl solution, and refluxed at 70° C. for 2 h. The reaction mixture was concentrated, treated with aqueous sodium bicarbonate solution to neutral pH and extracted with n-butanol. The organic layer was washed with water, dried, concentrated and purified using flash chromatography (silica gel, 20% methanol/chloroform) to obtain the title compound. Yield: 0.075 g, (13%); 1H NMR (DMSO-d6): δ 2.50-2.60 (m, 4H, 2CH2), 2.70 (s, 3H, CH3), 3.00-3.40 (m, 14H, 7CH2), 3.70 (s, 1H, OH), 3.90 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 7.10 (s, 1H, Ar), 7.20 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.20 (s, 1H, Ar); MS: m/e (EI+) 459 (M+1).

후처리

  1. customwas brought to room temperature
  2. concentrationconcentrated
  3. additiontreated with water
  4. customThe solid that separated
  5. washwas washed with water
  6. customdried
  7. additiontreated with methanolic HCl solution
  8. concentrationThe reaction mixture was concentrated
  9. additiontreated with aqueous sodium bicarbonate solution to neutral pH
  10. extractionextracted with n-butanol
  11. washThe organic layer was washed with water
  12. customdried
  13. concentrationconcentrated
  14. custompurified

출처 및 근거

ORD 기록
ord-645334b0977142ecb8415fa378275f97
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834001B2

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