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Sodium hydride → 1-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethyl}-1H-pyridin-4-one Hydrochloride

HRID 1869096
ノート
印刷プレビュー

反応式

HRID 1869096 の反応式
[H-].[Na+].[N:3]1[CH:8]=[CH:7][C:6](=[O:9])[CH2:5][CH:4]=1.Cl.[Cl:11][CH2:12][CH2:13][O:14][C:15]1[CH:24]=[C:23]2[C:18]([C:19]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]#[CH:33])[CH:27]=3)=[N:20][CH:21]=[N:22]2)=[CH:17][C:16]=1[O:34][CH2:35][CH2:36][O:37][CH3:38]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[ClH:11].[C:32]([C:28]1[CH:27]=[C:26]([NH:25][C:19]2[C:18]3[C:23](=[CH:24][C:15]([O:14][CH2:13][CH2:12][N:3]4[CH:4]=[CH:5][C:6](=[O:9])[CH:7]=[CH:8]4)=[C:16]([O:34][CH2:35][CH2:36][O:37][CH3:38])[CH:17]=3)[N:22]=[CH:21][N:20]=2)[CH:31]=[CH:30][CH:29]=1)#[CH:33]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 24758Sodium hydride2 回HCID 17984897Piridin-4-one2 回HCID 18925049[7-(2-Chloro-ethoxy)-6-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine Hydrochloride

生成物 1

HCID 189250871-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethyl}-1H-pyridin-4-one Hydrochloride収率 47.1%

試薬・触媒・溶媒 2

HCID 67553
Tetrabutylammonium Iodide
触媒
HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
22 °C

実験手順

NaH (30 mg of 60% in mineral oil, 0.77 mmol) was added to anhydrous DMF (2.0 mL) followed by pyrid-4-one (79 mg, 0.83 mmol). The mixture was stirred 40 minutes at 22° C. until all solids dissolved and the evolution of H2 ceased. The title product of Example 34 (120 mg, 0.28 mmol) and tetrabutylammonium iodide (15 mg) were added and the reaction mixture was stirred at 22° C. for 7 days under N2. Additional pyrid-4-one (79 mg) and NaH (30 mg of 60%) were dissolved in DMF (2 mL) and the solution was added to the reaction mixture. After another 4 days stirring the mixture was partitioned between CHCl3 and brine. The organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica utilizing 10% methanol/CH2Cl2 to afford 65 mg of the free base of the title product which was converted to the mono-hydrochloride salt according to the procedure described for Example 28 (66 mg; M.P. 240°-248° C. (dec); LC-MS: 457 (MH+); anal. RP-HPLC RT: 3.23 min)

後処理

  1. dissolutiondissolved
  2. stirringthe reaction mixture was stirred at 22° C. for 7 days under N2
  3. additionthe solution was added to the reaction mixture
  4. stirringAfter another 4 days stirring the mixture
  5. customwas partitioned between CHCl3 and brine
  6. dry with materialThe organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica utilizing 10% methanol/CH2Cl2

出典と根拠

ORDレコード
ord-e36ecee2a96c402ebcac4c3322e8b145
出典データセット
uspto-grants-2009_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
USRE041065E1

反応ノート

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