Water → 3,4,5,6-Tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid {2-[2-(tetrahydropyran-2-yloxy)-ethoxy]-pyridin-3-yl}amide

HRID 481075ノート

反応式

HRID 481075 の反応式
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:16]([NH2:17])=[CH:15][CH:14]=[CH:13][N:12]=1.C[Al](C)C.C([O:24][C:25]([C:27]1[C:36]2[C:35]3[N:37]=[CH:38][CH:39]=[CH:40][C:34]=3[CH2:33][CH2:32][CH2:31][C:30]=2[NH:29][CH:28]=1)=O)C.O>C(Cl)Cl>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:16]([NH:17][C:25]([C:27]2[C:36]3[C:35]4[N:37]=[CH:38][CH:39]=[CH:40][C:34]=4[CH2:33][CH2:32][CH2:31][C:30]=3[NH:29][CH:28]=2)=[O:24])=[CH:15][CH:14]=[CH:13][N:12]=1

参加物

6

反応物 4

HCID 962WaterHCID 16682925TrimethylaluminumHCID 206056123,4,5,6-Tetrahydro-3,10-diazabenzo[e]azulene-1-carboxylic acid ethyl esterHCID 223188362-[2-(Tetrahydropyran-2-yloxy)-ethoxy]pyridin-3-ylamine

生成物 1

HCID 865883163,4,5,6-Tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid {2-[2-(tetrahydropyran-2-yloxy)-ethoxy]-pyridin-3-yl}amide収率 97.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 2-[2-(tetrahydropyran-2-yloxy)-ethoxy]pyridin-3-ylamine (2.3 g, 9.7 mmol) in DCM (8 mL) is added AlMe3 (2M in toluene, 4.9 mL) at rt. After stirring at room temperature for 1 h, a solution of 3,4,5,6-tetrahydro-3,10-diazabenzo[e]azulene-1-carboxylic acid ethyl ester (500 mg, 1.95 mmol) in DCM (10 mL) is added. The mixture is refluxed overnight. On cooling, water (5 mL) is added, and the resulting mixture is extracted with DCM. The combined DCM extracts are dried and solvent removed. The residue is separated by column chromatography on silica gel (5% methanol in DCM) to give 850 mg of 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid {2-[2-(tetrahydropyran-2-yloxy)-ethoxy]-pyridin-3-yl}amide as an oil.

後処理

  1. temperatureThe mixture is refluxed overnight
  2. temperatureOn cooling
  3. extractionthe resulting mixture is extracted with DCM
  4. dry with materialThe combined DCM extracts are dried
  5. customsolvent removed
  6. customThe residue is separated by column chromatography on silica gel (5% methanol in DCM)

出典と根拠

ORDレコード
ord-526baeee427b494ca58f6b1c9a4d97ff
出典データセット
uspto-grants-2003_11
特許番号
US06653471B2

反応ノート

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