Water → 2-((4-(1,3-dimethyl-4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline

HRID 1170363노트

반응식

HRID 1170363 반응식
[CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[C:5]([C:13]2[CH:30]=[CH:29][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:14]=2)[NH:4][N:3]=1.[H-].[Na+].[CH3:33]I.O>CN(C)C=O>[CH3:33][N:4]1[C:5]([C:13]2[CH:30]=[CH:29][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:14]=2)=[C:6]([C:7]2[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=2)[C:2]([CH3:1])=[N:3]1

참가 물질

6

반응물 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydride2회HCID 178434588HCID 178434588, 화합물

생성물 1

HCID 116829072-((4-(1,3-dimethyl-4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 2-((4-(3-methyl-4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline (150 mg, 0.38 mmol) in anhydrous dimethylformamide (2 mL) was treated at 0° C. with sodium hydride dispersion (30 mg, 0.76 mmol of 60% NaH in oil) followed after 20 min with methyl iodide (54 mg, 0.38 mmol), and the stirred mixture was allowed to warm to RT overnight. Water was added and the mixture extracted with dichloromethane (3×20 mL). The organic layer was dried, concentrated, and the residue chromatographed on silica eluted with an ethyl acetate-hexane gradient containing 1% triethylamine, giving fractions containing two isomeric substances. The less polar isomer (18 mg) was thus obtained (methylation regiochemistry tentatively assigned by NMR). 1H NMR (CDCl3, 400 mHz) δ 8.41 (m, 2H), 8.21 (d, 1H, J=8.7 Hz), 8.07 (d, 1H, J=8.3 Hz), 7.84 (d, 1H, J=9.5 Hz), 7.74 (ddd, 1H), 7.67 (d, 1H, J=8.3 Hz), 7.55 (ddd, 1H), 7.12 (m, 2H), 7.05 (m, 2H), 7.0 (m, 2H), 5.40 (s, 2H), 3.71 (s, 3H), 2.37 (s, 3H). HPLC-MS 4.81 min, m/e 407 (MH+).

후처리

  1. extractionthe mixture extracted with dichloromethane (3×20 mL)
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customthe residue chromatographed on silica
  5. washeluted with an ethyl acetate-hexane gradient
  6. additioncontaining 1% triethylamine
  7. customgiving fractions
  8. additioncontaining two isomeric substances
  9. customThe less polar isomer (18 mg) was thus obtained (methylation regiochemistry
  10. customHPLC-MS 4.81 min, m/e 407 (MH+)

출처 및 근거

ORD 기록
ord-17d222ab14e94e2bb8622a8979695e1d
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07825254B2

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