Toluene → 6-oxo-N-(quinolin-3-yl)-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamide

HRID 1521764ノート

反応式

HRID 1521764 の反応式
C[C:2]1(C)[CH2:8][N:7]2[C:9]3[N:15]=[C:14]([C:16]([OH:18])=O)[CH:13]=[CH:12][C:10]=3[CH:11]=[C:6]2[C:5](=[O:19])[NH:4][CH2:3]1.S(Cl)(Cl)=O.[C:25]([C:29]1ON=[C:31]([NH2:34])[CH:30]=1)([CH3:28])([CH3:27])C.C([N:38](CC)C(C)C)(C)C.[C:44]1([CH3:50])C=CC=C[CH:45]=1>>[O:19]=[C:5]1[NH:4][CH2:3][CH2:2][CH2:8][N:7]2[C:9]3[N:15]=[C:14]([C:16]([NH:38][C:30]4[CH:31]=[N:34][C:27]5[C:25]([CH:29]=4)=[CH:28][CH:50]=[CH:44][CH:45]=5)=[O:18])[CH:13]=[CH:12][C:10]=3[CH:11]=[C:6]12

参加物

6

反応物 5

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 672363209,9-Dimethyl-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid2 回

生成物 1

HCID 532421996-oxo-N-(quinolin-3-yl)-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamide収率 11%

実験手順

To a suspension of 9,9-dimethyl-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3′,2′:4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid (Intermediate F, 50 mg, 0.18 mmol) in toluene (1 mL) is added thionyl chloride (27 μL, 0.37 mmol) and the mixture is heated at reflux. After 2 h, the mixture is cooled to room temperature and is concentrated under reduced pressure. Toluene (1 mL) is added to the residue and it is concentrated once again under reduced pressure. Toluene (2 mL) is added once more and the volume is reduced by half. 5-tert-butyl-3-aminoisoxazole (51 mg, 0.37 mmol) and N,N-diisopropylethylamine (64 μL, 0.37 mmol) are added and the reaction is stirred at room temperature for 16 h. The reaction mixture is evaporated and the residue is purified via preparative HPLC using a gradient elution from 10-75% acetonitrile/H2O with 0.1% TFA to afford the title compound (8 mg, 11%). LCMS: 396.83 (M+H+).

後処理

  1. temperaturethe mixture is heated
  2. temperatureat reflux
  3. concentrationis concentrated under reduced pressure
  4. additionToluene (1 mL) is added to the residue and it
  5. concentrationis concentrated once again under reduced pressure
  6. additionToluene (2 mL) is added once more
  7. customThe reaction mixture is evaporated
  8. customthe residue is purified via preparative HPLC
  9. washa gradient elution from 10-75% acetonitrile/H2O with 0.1% TFA

出典と根拠

ORDレコード
ord-2b156a7c74d6431ab7b88a2f21c96bf4
出典データセット
uspto-grants-2015_07
特許番号
US09073926B2

反応ノート

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