Potassium tert-butoxide → 7-(2-(azetidin-1-yl)ethoxy)-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79432Notes

Reaction equation

HRID 79432 reaction equation
[N:1]1([CH2:5][CH2:6][OH:7])[CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].F[C:15]1[CH:20]=[CH:19][N:18]2[C:21]([C:24]([NH:26][C:27]3[CH:35]=[CH:34][CH:33]=[C:32]4[C:28]=3[C:29]([CH:44]3[CH2:46][CH2:45]3)=[N:30][N:31]4[CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[N:38]=3)=[O:25])=[CH:22][N:23]=[C:17]2[CH:16]=1>C(O)(C)(C)C>[N:1]1([CH2:5][CH2:6][O:7][C:15]2[CH:20]=[CH:19][N:18]3[C:21]([C:24]([NH:26][C:27]4[CH:35]=[CH:34][CH:33]=[C:32]5[C:28]=4[C:29]([CH:44]4[CH2:45][CH2:46]4)=[N:30][N:31]5[CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[N:38]=4)=[O:25])=[CH:22][N:23]=[C:17]3[CH:16]=2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 545691132-(Azetidin-1-yl)ethan-1-olHCID 672611757-Fluoro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 672606517-(2-(azetidin-1-yl)ethoxy)-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
88 °C

Procedure

2-(Azetidin-1-yl)ethanol (52 mg, 0.51 mmol) was dissolved in tert-butanol (0.3 mL) and treated with potassium tert-butoxide (51 mg, 0.45 mmol). The mixture was stirred at 88° C. for 5 minutes before adding 7-fluoro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide in one portion. The mixture was stirred at 88° C. for 16 hours. The mixture was cooled to ambient temperature and quenched with water (2 mL) followed by vigorous stirring for 2 hours at ambient temperature. The precipitate was isolated by filtration and dried under vacuum to give a pale yellow residue which was triturated with diethyl ether 3 times to give a solid. Purification by Preparative Thin Layer Chromatography (Silica, 20×20, 0.5 mm thickness) eluting with 10% MeOH/DCM with 0.6% ammonium hydroxide gave 7-(2-(azetidin-1-yl)ethoxy)-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (18 mg). MS (APCI), positive scan, m/z=522.2 (M+1).

Workup

  1. stirringThe mixture was stirred at 88° C. for 16 hours
  2. temperatureThe mixture was cooled to ambient temperature
  3. customquenched with water (2 mL)
  4. stirringby vigorous stirring for 2 hours at ambient temperature
  5. customThe precipitate was isolated by filtration
  6. customdried under vacuum
  7. customto give a pale yellow residue which
  8. customwas triturated with diethyl ether 3 times
  9. customto give a solid
  10. customPurification by Preparative Thin Layer Chromatography (Silica, 20×20, 0.5 mm thickness)
  11. washeluting with 10% MeOH/DCM with 0.6% ammonium hydroxide

Sources & evidence

ORD record
ord-b167e2392e7d4ca989b777216ec52135
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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