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

HRID 1288887노트

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HRID 1288887 반응식
[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]

참가 물질

6

반응물 3

HCID 24758Sodium hydride2회HCID 17984897Piridin-4-one2회HCID 18925049[7-(2-Chloro-ethoxy)-6-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine Hydrochloride

생성물 1

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

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매2회

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온도
22 °C

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-6279ff6b4f314ef39e165ef3fa60473b
출처 데이터셋
uspto-grants-1998_05
특허 번호
US05747498

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