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

HRID 706539Notes

Reaction equation

HRID 706539 reaction equation
[CH:1]([C:4]1[N:9]=[C:8]([CH2:10][N:11]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([NH2:20])[C:14]=3[C:13]([CH3:21])=[N:12]2)[CH:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[F:22][C:23]1[CH:28]=[CH:27][N:26]2[C:29]([C:32](OCC)=[O:33])=[CH:30][N:31]=[C:25]2[CH:24]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:22][C:23]1[CH:28]=[CH:27][N:26]2[C:29]([C:32]([NH:20][C:15]3[CH:16]=[CH:17][CH:18]=[C:19]4[C:14]=3[C:13]([CH3:21])=[N:12][N:11]4[CH2:10][C:8]3[CH:7]=[CH:6][CH:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[N:9]=3)=[O:33])=[CH:30][N:31]=[C:25]2[CH:24]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 67259301Ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylateHCID 679746421-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-amine

Product 1

HCID 679760637-fluoro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1-((6-Isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-amine (Preparation D; 0.673 g, 2.40 mmol) and ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylate (Step C, 0.500 g, 2.40 mmol) were dissolved in dry THF (24 mL) and chilled to 0° C. LiHMDS (5.28 mL, 5.28 mmol, 1M in THF) was added by syringe over a five-minute period. Once the addition was complete, the reaction mixture was removed from the cooling bath and allowed to warm to ambient temperature. The mixture was quenched with saturated ammonium chloride solution and extracted with EtOAc. The combined organic extracts were washed with saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated. The crude material was purified by column chromatography (100% ethyl acetate) to afford 775 mg (73%) of 7-fluoro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide.

Workup

  1. additionOnce the addition
  2. customthe reaction mixture was removed from the cooling bath
  3. temperatureto warm to ambient temperature
  4. customThe mixture was quenched with saturated ammonium chloride solution
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with saturated sodium bicarbonate solution
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography (100% ethyl acetate)

Sources & evidence

ORD record
ord-92f5f877acd3440590d8e65c117afe32
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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