Methyl iodide → HCID 57917420, 화합물

HRID 69244노트

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HRID 69244 반응식
[H-].[Na+].[N:3]1[NH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[CH:9][C:8]([C@@H:12]([C:14]1[N:18]3[N:19]=[C:20]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:21]=[CH:22][C:17]3=[N:16][CH:15]=1)[CH3:13])=[CH:7]2.CI.[CH2:31](Cl)Cl>C1COCC1.[Cl-].[Na+].O>[CH3:31][N:3]1[C:11]2[C:6](=[CH:7][C:8]([C@@H:12]([C:14]3[N:18]4[N:19]=[C:20]([C:23]5[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=5)[CH:21]=[CH:22][C:17]4=[N:16][CH:15]=3)[CH3:13])=[CH:9][CH:10]=2)[CH:5]=[N:4]1

참가 물질

7

반응물 4

HCID 6328Methyl iodideHCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 178461646HCID 178461646, 화합물

생성물 1

HCID 57917420HCID 57917420, 화합물

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 57417360Sodium chloride; water용매

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온도
0 °C

실험 절차

To a mixture of NaH (4.8 mg, 0.1 mmol) in THF (0.5 mL) cooled to 0° C. was added (3-[(S)-1-(2H-indazol-5-yl)-ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 195, 34.3 mg, 0.10 mmol). The RM was allowed to warm up to rt and stirred 15 min. Then it was cooled down again and methyliodide (21.3 mg, 0.150 mmol) was added dropwise. The RM was allowed to warm up to rt and stirred for 5 h. It was then taken into DCM and brine, extracted, and the organics were joined dried over MgSO4. The solvent was removed and the residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in EtOAc) to afford the title compound after evaporation of the solvent and drying of the material under vacuum (tR 3.72 min (conditions 3), MH+=358, 1H-NMR in DMSO-d6: 8.35 (s, 1H); 8.03 (d, 1H); 8.00 (s, 1H); 7.94 (s, 1H); 7.73 (s, 1H); 7.70 (s, 1H); 7.52 (d, 1H); 7.45 (d, 1H); 7.43 (d, 1H); 4.73 (q, 1H); 4.74 (s, 3H); 3.89 (s, 3H); 1.77 (d, 3H)).

후처리

  1. temperatureto warm up to rt
  2. temperatureThen it was cooled down again
  3. temperatureto warm up to rt
  4. stirringstirred for 5 h
  5. extractionextracted
  6. dry with materialthe organics were joined dried over MgSO4
  7. customThe solvent was removed
  8. customthe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in EtOAc)

출처 및 근거

ORD 기록
ord-6a7634ad9d40413c85553362341f9d65
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822468B2

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