Ammonium Chloride → N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79355

반응식

HRID 79355 반응식
[CH2:1]([C:3]1[C:11]2[C:10]([NH2:12])=[CH:9][CH:8]=[CH:7][C:6]=2[N:5]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=2)[N:4]=1)[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][O:40][C:41]2[CH:46]=[CH:45][N:44]3[C:47]([C:50](OCC)=[O:51])=[CH:48][N:49]=[C:43]3[CH:42]=2)[CH2:34][CH2:33]1.[Cl-].[NH4+]>C1COCC1>[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:50]([C:47]2[N:44]3[CH:45]=[CH:46][C:41]([O:40][CH2:39][CH2:38][N:35]4[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]4)=[CH:42][C:43]3=[N:49][CH:48]=2)=[O:51])[N:5]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=2)[N:4]=1)[CH3:2]

참가 물질

6

반응물 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 67254998Ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 672598043-ethyl-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine

생성물 1

HCID 53262025N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a cooled (ice/water bath) solution of 3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (0.080 g; 0.30 mmol) in anhydrous THF (2 mL) under nitrogen was added drop wise LHMDS (1.0 M solution in THF; 0.32 mmol). The mixture was stirred with cooling for 10 minutes and then added to a solution of ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (Preparation D) in anhydrous THF (2 mL) with ice/water cooling. An excess of saturated aqueous ammonium chloride solution was added to quench the reaction. The mixture was extracted with DCM. The aqueous phase was then rendered basic by the addition of saturated aqueous sodium carbonate solution and extracted multiple times with DCM and EtOAc. The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography on silica, eluting with DCM/MeOH/NH4OH (100:8:1). Purification by thin layer chromatography of the isolated material was repeated under the same conditions to provide N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide (53 mg). MS (ES+APCI) m/z=553.1 (M+H).

후처리

  1. temperaturewith cooling for 10 minutes
  2. customto quench
  3. customthe reaction
  4. extractionThe mixture was extracted with DCM
  5. additionThe aqueous phase was then rendered basic by the addition of saturated aqueous sodium carbonate solution
  6. extractionextracted multiple times with DCM and EtOAc
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative thin layer chromatography on silica
  10. washeluting with DCM/MeOH/NH4OH (100:8:1)
  11. customPurification by thin layer chromatography of the isolated material

출처 및 근거

ORD 기록
ord-c0604c460a664d2594a2046eb0f59bf1
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841455B2

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