Lithium Hexamethyldisilazide → N-(3-iodo-1-((2-methylthiazol-5-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79453Notes

Reaction equation

HRID 79453 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[I:11][C:12]1[C:20]2[C:19]([NH2:21])=[CH:18][CH:17]=[CH:16][C:15]=2[N:14]([CH2:22][C:23]2[S:27][C:26]([CH3:28])=[N:25][CH:24]=2)[N:13]=1.[CH3:29][N:30]1[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][O:38][C:39]2[CH:44]=[CH:43][N:42]3[C:45]([C:48](OCC)=[O:49])=[CH:46][N:47]=[C:41]3[CH:40]=2)[CH2:32][CH2:31]1>C1COCC1.O>[I:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][C:19]=2[NH:21][C:48]([C:45]2[N:42]3[CH:43]=[CH:44][C:39]([O:38][CH2:37][CH2:36][N:33]4[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]4)=[CH:40][C:41]3=[N:47][CH:46]=2)=[O:49])[N:14]([CH2:22][C:23]2[S:27][C:26]([CH3:28])=[N:25][CH:24]=2)[N:13]=1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 67254998Ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 672609553-iodo-1-((2-methylthiazol-5-yl)methyl)-1H-indazol-4-amine

Product 1

HCID 67261270N-(3-iodo-1-((2-methylthiazol-5-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideYield 16.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Lithium bis(trimethylsilyl)amide (1.0 M in THF, 0.24 mL) was added dropwise at ambient temperature and under a nitrogen atmosphere to a solution of 3-iodo-1-((2-methylthiazol-5-yl)methyl)-1H-indazol-4-amine (40 mg, 0.108 mmol) in anhydrous THF (3 mL). The resulting brown mixture was added via syringe to a cooled (ice-water bath) solution of ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (Preparation D; 35.9 mg, 0.108 mmol) in anhydrous THF (3 mL). The reaction mixture was allowed to warm to ambient temperature overnight. The reaction mixture was diluted with water, and extracted multiple times with dichloromethane. The dichloromethane extracts were dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude residue was purified by preparative thin-layer chromatography (silica, 7 N ammonia/MeOH:MeOH:DCM in a 3:7:90 ratio as eluent) to afford the product (11.6 mg) as a tan solid. MS (ES+APCI) m/z=657 (M+H).

Workup

  1. additionThe resulting brown mixture was added via syringe to
  2. extractionextracted multiple times with dichloromethane
  3. dry with materialThe dichloromethane extracts were dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by preparative thin-layer chromatography (silica, 7 N ammonia/MeOH

Sources & evidence

ORD record
ord-baf11e972f794ce482db454c84623740
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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