Ammonia → 4-Chloro-6-methyl-10,10-dioxo-2-piperazin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclo heptene-8-carboxylic acid methyl ester

HRID 1172505노트

반응식

HRID 1172505 반응식
[NH3:1].Cl[CH2:3][CH2:4][N:5]([CH2:28][CH2:29]Cl)[C:6]1[CH:26]=[C:25]([Cl:27])[C:9]2[O:10][C:11]3[C:20]([CH3:21])=[CH:19][C:18]([C:22]([OH:24])=[O:23])=[CH:17][C:12]=3[S:13](=[O:16])(=[O:15])[CH2:14][C:8]=2[CH:7]=1.[CH3:31]O>>[CH3:31][O:24][C:22]([C:18]1[CH:19]=[C:20]([CH3:21])[C:11]2[O:10][C:9]3[C:25]([Cl:27])=[CH:26][C:6]([N:5]4[CH2:4][CH2:3][NH:1][CH2:29][CH2:28]4)=[CH:7][C:8]=3[CH2:14][S:13](=[O:15])(=[O:16])[C:12]=2[CH:17]=1)=[O:23]

참가 물질

4

반응물 3

HCID 222AmmoniaHCID 887MethanolHCID 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 115410724-Chloro-6-methyl-10,10-dioxo-2-piperazin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclo heptene-8-carboxylic acid methyl ester

반응 조건

온도
110 °C

실험 절차

Aqueous ammonia solution (30%, 4 mL) was added to a solution of Example 102j (0.5 g, 1.04 mmol) in methanol (1 mL), in an atmosphere of nitrogen, sealed in a pressure reactor vessel and heated at 110° C. for 6 h. The reaction mixture was brought to room temperature, concentrated, treated with chilled water and dilute HCl to neutral pH. The solid that precipitated was filtered, washed with water and dried. It was treated with methanolic HCl solution and stirred at 70° C. for 2.5 h. The reaction mixture was cooled and the solid that separated was filtered, washed with methanol, dried and purified using flash chromatography (silica gel, MeOH/CHCl3) to obtain the title compound as an off white solid. Yield: 0.220 g (48.24%); 1H NMR (DMSO-d6): δ 2.30 (m, 4H, 2CH2), 2.70 (s, 3H, CH3), 3.10 (m, 4H, 2CH2), 3.95 (s, 3H, OCH3), 5.10 (s, 2H, CH2), 7.10 (s, 1H, Ar), 7.20 (s, 1H, Ar), 8.05 (s, 1H, Ar) 8.20 (s, 1H, Ar): MS: m/e (ES+) 422 (M+1).

후처리

  1. customsealed in a pressure reactor vessel
  2. customwas brought to room temperature
  3. concentrationconcentrated
  4. additiontreated with chilled water and dilute HCl to neutral pH
  5. customThe solid that precipitated
  6. filtrationwas filtered
  7. washwashed with water
  8. customdried
  9. additionIt was treated with methanolic HCl solution
  10. temperatureThe reaction mixture was cooled
  11. customthe solid that separated
  12. filtrationwas filtered
  13. washwashed with methanol
  14. customdried
  15. custompurified

출처 및 근거

ORD 기록
ord-a99dbbbcf49947198f28e46d00d97592
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834001B2

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