Lithium Hexamethyldisilazide → 7-chloro-N-(1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706590Notes

Reaction equation

HRID 706590 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[NH2:11])[N:4]([CH2:12][C:13]2[CH:17]=[CH:16][N:15]([CH:18]([CH3:20])[CH3:19])[N:14]=2)[N:3]=1.[Cl:21][C:22]1[CH:27]=[CH:26][N:25]2[C:28]([C:31](OCC)=[O:32])=[CH:29][N:30]=[C:24]2[CH:23]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:21][C:22]1[CH:27]=[CH:26][N:25]2[C:28]([C:31]([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:17]=[CH:16][N:15]([CH:18]([CH3:20])[CH3:19])[N:14]=3)=[O:32])=[CH:29][N:30]=[C:24]2[CH:23]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 67107280Ethyl 7-chloroimidazo[1,2-A]pyridine-3-carboxylateHCID 866993293-Methyl-1-((1-isopropylpyrazole-3-yl)methyl)-4-amino-1H-indazole

Product 1

HCID 679740927-chloro-N-(1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-Methyl-1-((1-isopropylpyrazole-3-yl)methyl)-4-amino-1H-indazole (1 equivalent) and ethyl 7-chloroimidazo[1,2-a]pyridine-3-carboxylate (Example 7 step D; 1 equivalent) were dissolved in dry THF (0.2 M) and the resulting solution was cooled to 0° C. Lithium bis(trimethylsilyl)amide (2.3 equivalents) was slowly added and the resulting mixture was allowed to warm to ambient temperature overnight. THF was removed under vacuum and the remaining material was partitioned between water and ethyl acetate. The bottom aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were combined, dried over sodium sulfate, filtered and \ concentrated to give desired compound (52% yield).

Workup

  1. temperatureto warm to ambient temperature overnight
  2. customTHF was removed under vacuum
  3. customthe remaining material was partitioned between water and ethyl acetate
  4. extractionThe bottom aqueous layer was extracted twice with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentration\ concentrated

Sources & evidence

ORD record
ord-2f49b428d034488fab4c6531f458e028
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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