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

HRID 1172522ノート

反応式

HRID 1172522 の反応式
[CH:1]1([NH2:5])[CH2:4][CH2:3][CH2:2]1.Cl[CH2:7][CH2:8][N:9]([CH2:32][CH2:33]Cl)[C:10]1[CH:30]=[C:29]([Cl:31])[C:13]2[O:14][C:15]3[C:24]([CH3:25])=[CH:23][C:22]([C:26]([OH:28])=[O:27])=[CH:21][C:16]=3[S:17](=[O:20])(=[O:19])[CH2:18][C:12]=2[CH:11]=1.[CH3:35]O>>[CH3:35][O:28][C:26]([C:22]1[CH:23]=[C:24]([CH3:25])[C:15]2[O:14][C:13]3[C:29]([Cl:31])=[CH:30][C:10]([N:9]4[CH2:8][CH2:7][N:5]([CH:1]5[CH2:4][CH2:3][CH2:2]5)[CH2:33][CH2:32]4)=[CH:11][C:12]=3[CH2:18][S:17](=[O:20])(=[O:19])[C:16]=2[CH:21]=1)=[O:27]

参加物

4

反応物 3

HCID 887MethanolHCID 75645CyclobutylamineHCID 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

生成物 1

HCID 1317284924-Chloro-2-(4-cyclobutyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

反応条件

温度
70 °C

実験手順

Cyclobutylamine (1 mL, excess) was added to a solution of Example 102j (0.6 g, 1.25 mmol) in methanol (10 mL), followed by the addition of n-tetrabutylammonium iodide (0.01 g, 0.027 mmol) in an atmosphere of nitrogen and sealed in a pressure reactor vessel at 110° C. for 6 h. It was brought to room temperature, concentrated, treated with methanolic HCl solution, and refluxed at 70° C. for 6 h. The reaction mixture was concentrated, treated with water, aqueous sodium bicarbonate solution to neutral pH and the solid that separated was washed with water dried, and purified using flash chromatography (silica gel, methanol/chloroform) to obtain the title compound as a white solid. Yield: 0.410 g, (25%); 1H NMR (DMSO-d6): δ 1.60-2.10 (m, 6H, 3CH2), 2.40-2.50 (m, 4H, 2CH2), 2.80 (m, 1H, CH), 3.20-3.30 (m, 4H, 2CH2), 3.90 (s, 3H, OCH3), 4.70 (s, 2H, CH2), 6.80 (s, 1H, Ar), 6.90 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.50 (s, 1H, Ar); MS: m/e (CI+) 491 (M+1).

後処理

  1. customsealed in a pressure reactor vessel at 110° C. for 6 h
  2. customwas brought to room temperature
  3. concentrationconcentrated
  4. additiontreated with methanolic HCl solution
  5. concentrationThe reaction mixture was concentrated
  6. additiontreated with water, aqueous sodium bicarbonate solution to neutral pH
  7. customthe solid that separated
  8. washwas washed with water
  9. customdried
  10. custompurified

出典と根拠

ORDレコード
ord-643b17d2173a4e5e98844e647e9ab659
出典データセット
uspto-grants-2010_11
特許番号
US07834001B2

反応ノート

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