Lithium Hexamethyldisilazide → 7-bromo-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706624Notes

Reaction equation

HRID 706624 reaction equation
[CH3:1][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[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[N:14]=2)[N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:30][C:31]1[CH:36]=[CH:35][N:34]2[C:37]([C:40](OC)=[O:41])=[CH:38][N:39]=[C:33]2[CH:32]=1.CO.C(Cl)Cl>C1COCC1>[Br:30][C:31]1[CH:36]=[CH:35][N:34]2[C:37]([C:40]([NH:11][C:9]3[CH:8]=[CH:7][CH:6]=[C:5]4[C:10]=3[C:2]([CH3:1])=[N:3][N:4]4[CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[N:14]=3)=[O:41])=[CH:38][N:39]=[C:33]2[CH:32]=1

Participants

6

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 21226129Dichloromethane methanolHCID 67259752Methyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylateHCID 672609383-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine

Product 1

HCID 679764107-bromo-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 68.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (197.8 mg, 0.784 mmol) in anhydrous THF (3 ml) was added lithium bis(trimethylsilyl)amide (1.0 M in THF, 1.6 mL) under a nitrogen atmosphere at ambient temperature. The resulting mixture was stirred at ambient temperature for 10 minutes, then added dropwise to a chilled (ice-water bath) solution of methyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylate (200 mg, 0.784 mmol) in anhydrous THF (3 mL). The cold bath was removed, and the reaction mixture was allowed to warm to ambient temperature, and quenched with water. The resulting suspension was extracted with DCM. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford the crude product. The crude product was subjected to preparative thin-layer chromatography on silica with 8% MeOH/DCM as the eluent to afford 255.6 mg of desired product as a yellow solid.

Workup

  1. additionadded dropwise to
  2. customThe cold bath was removed
  3. temperatureto warm to ambient temperature
  4. customquenched with water
  5. extractionThe resulting suspension was extracted with DCM
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto afford the crude product

Sources & evidence

ORD record
ord-bf6618f4955a410cb41e79d2e3fd0b60
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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