Trifluoroacetic acid → 2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)-8-(pyrrolidin-3-ylmethoxy)quinoline

HRID 1095689

반응식

HRID 1095689 반응식
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[C:18]([O:25][CH2:26][CH:27]5O[CH2:31][CH2:30][NH:29][CH2:28]5)[CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(OCC1CCN(C(OC(C)(C)C)=O)C1)(=O)=O.C(O)(C(F)(F)F)=O>CC(N(C)C)=O.C(Cl)Cl.O>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[C:18]([O:25][CH2:26][CH:27]5[CH2:31][CH2:30][NH:29][CH2:28]5)[CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 4183641tert-Butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 250981592-((2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)methyl)morpholine

생성물 1

HCID 250984322-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)-8-(pyrrolidin-3-ylmethoxy)quinoline수율 36%

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 31374Dimethylacetamide용매

반응 조건

온도
70 °C

실험 절차

To a solution of 2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol [prepared as in Example 16; 204 mg, 0.61 mmol] in anhydrous DMA (5 mL) was added cesium carbonate (0.60 g, 1.8 mmol) followed by tert-butyl 3-((methylsulfonyloxy)methyl)pyrrolidine-1-carboxylate (221 mg, 0.79 mmol). The heterogeneous mixture was stirred at 70° C. for 20 hours and allowed to cool. The mixture was treated with water (50 mL) and extracted with chloroform and EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated to afford the crude product (386 mg, 122% yield) as a viscous oil. MS ESI (+) m/z 519.1 (M+1) detected. The oil (315 mg) was dissolved in CH2Cl2 (2 mL) and treated with TFA (1 mL). After stirring for 2 hours at ambient temperature the mixture was concentrated. The residue was treated with excess (20 ml) saturated aqueous sodium bicarbonate solution, and the resulting mixture was extracted with chloroform and EtOAc. The combined organic extracts were dried over anhydrous Na2SO4 and concentrated to afford a viscous oil. The oil was purified by column chromatography on silica gel (elution with 7 N NH3/MeOH-chloroform) to provide the title compound (74 mg, 36% yield over two steps) as a solid. MS ESI (+) m/z 419.3 (M+1). detected.

후처리

  1. temperatureto cool
  2. extractionextracted with chloroform and EtOAc
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford the crude product (386 mg, 122% yield) as a viscous oil
  7. stirringAfter stirring for 2 hours at ambient temperature the mixture
  8. concentrationwas concentrated
  9. additionThe residue was treated with excess (20 ml) saturated aqueous sodium bicarbonate solution
  10. extractionthe resulting mixture was extracted with chloroform and EtOAc
  11. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  12. concentrationconcentrated
  13. customto afford a viscous oil
  14. customThe oil was purified by column chromatography on silica gel (elution with 7 N NH3/MeOH-chloroform)

출처 및 근거

ORD 기록
ord-595d7a6a1ef3479c85794158e78f1419
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08138181B2

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