Dimethyl Sulfoxide → (S)-7-(2-(3,4-dimethylpiperazin-1-yl)ethoxy)-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706560Notes

Reaction equation

HRID 706560 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH3:33])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]([CH3:32])[CH3:31])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:34][C@@H:35]1[N:40]([CH3:41])[CH2:39][CH2:38][N:37]([CH2:42][CH2:43][OH:44])[CH2:36]1.[OH-].[K+].CS(C)=O>O>[CH3:34][C@@H:35]1[N:40]([CH3:41])[CH2:39][CH2:38][N:37]([CH2:42][CH2:43][O:44][C:2]2[CH:7]=[CH:6][N:5]3[C:8]([C:11]([NH:13][C:14]4[CH:22]=[CH:21][CH:20]=[C:19]5[C:15]=4[C:16]([CH3:33])=[N:17][N:18]5[CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]([CH3:32])[CH3:31])[N:25]=4)=[O:12])=[CH:9][N:10]=[C:4]3[CH:3]=2)[CH2:36]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 14797Potassium HydroxideHCID 67975003(S)-2-(3,4-dimethylpiperazin-1-yl)ethanolHCID 679758637-chloro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 57384858(S)-7-(2-(3,4-dimethylpiperazin-1-yl)ethoxy)-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 53%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

A flask equipped with a condenser was charged with the 7-chloro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (15.0 g, 32.68 mmol), (S)-2-(3,4-dimethylpiperazin-1-yl)ethanol (10.34 g, 65.37 mmol, Example 23), crushed KOH (9.17 g, 163.4 mmol) and 100 mL of DMSO. The mixture was heated to 95° C. for 22 hours. The mixture was allowed to cool to ambient temperature, 350 mL of water were added and the mixture stirred vigorously for 30 minutes. The mixture was extracted with EtOAc, and the combined organic extracts were washed with brine and 10% aqueous potassium carbonate, dried and concentrated. The resulting material was purified by column chromatography (10% MeOH/DCM/0.5% NH4OH to 15% MeOH/DCM/0.5% NH4OH) and then triturated with ether. The resulting solid was collected to give 10 g (53%) of the title compound. MS (APCI), positive scan, m/z=581.1 (M+H). [α]D=+5.6° (c=1.0, CHCl3).

Workup

  1. customA flask equipped with a condenser
  2. temperatureto cool to ambient temperature
  3. extractionThe mixture was extracted with EtOAc
  4. washthe combined organic extracts were washed with brine and 10% aqueous potassium carbonate
  5. customdried
  6. concentrationconcentrated
  7. customThe resulting material was purified by column chromatography (10% MeOH/DCM/0.5% NH4OH to 15% MeOH/DCM/0.5% NH4OH)
  8. customtriturated with ether
  9. customThe resulting solid was collected

Sources & evidence

ORD record
ord-0bad49925bbd4620b3ce9ea93d0c7e1a
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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