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 706742Notes

Reaction equation

HRID 706742 reaction equation
[I:1][C:2]1[C:10]2[C:9]([NH2:11])=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]([CH2:12][C:13]2[S:17][C:16]([CH3:18])=[N:15][CH:14]=2)[N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[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.CO.C(Cl)Cl>C1COCC1.O>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[NH:11][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:4]([CH2:12][C:13]2[S:17][C:16]([CH3:18])=[N:15][CH:14]=2)[N:3]=1

Participants

7

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 21226129Dichloromethane methanolHCID 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 16.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-iodo-1-((2-methylthiazol-5-yl)methyl)-1H-indazol-4-amine (40 mg, 0.11 mmol) in anhydrous THF (3 mL) was treated at ambient temperature under a nitrogen atmosphere with lithium bis(trimethylsilyl)amide (1.0 M in THF, 0.24 mL). The resulting brown solution was added dropwise to a cooled (ice-water) solution of ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (35.9 mg, 0.11 mmol) in anhydrous THF (3 mL). The reaction mixture was allowed to warm to ambient temperature, and was diluted with water (10 ml). The resulting mixture was extracted thoroughly with ethyl acetate and dichloromethane. The combined organic extracts were dried over sodium sulfate, the solids removed by filtration, and the filtrate was concentrated to afford an oil. The crude oil was subjected to preparative thin-layer chromatography on silica with MeOH/DCM as the eluent to afford 11.6 mg of the desired product.

Workup

  1. additionThe resulting brown solution was added dropwise to
  2. extractionThe resulting mixture was extracted thoroughly with ethyl acetate and dichloromethane
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. customthe solids removed by filtration
  5. concentrationthe filtrate was concentrated
  6. customto afford an oil

Sources & evidence

ORD record
ord-38627cd3494b4e789b32fec445113009
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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