Potassium Hydroxide → N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)-7-(2-((3S,5R)-3,4,5-trimethylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706546Notes

Reaction equation

HRID 706546 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])[C@@H:39]([CH3:42])[CH2:38][N:37]([CH2:43][CH2:44][OH:45])[CH2:36]1.[OH-].[K+]>CS(C)=O.O>[CH:30]([C:26]1[N:25]=[C:24]([CH2:23][N:18]2[C:19]3[C:15](=[C:14]([NH:13][C:11]([C:8]4[N:5]5[CH:6]=[CH:7][C:2]([O:45][CH2:44][CH2:43][N:37]6[CH2:38][C@@H:39]([CH3:42])[N:40]([CH3:41])[C@@H:35]([CH3:34])[CH2:36]6)=[CH:3][C:4]5=[N:10][CH:9]=4)=[O:12])[CH:22]=[CH:21][CH:20]=3)[C:16]([CH3:33])=[N:17]2)[CH:29]=[CH:28][CH:27]=1)([CH3:32])[CH3:31]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 679740542-((3R,5S)-3,4,5-trimethylpiperazin-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 57387642N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)-7-(2-((3S,5R)-3,4,5-trimethylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideYield 6.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

A pressure tube was charged with 7-chloro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (0.500 g, 1.09 mmol), 2-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)ethanol (0.375 g, 2.18 mmol), crushed potassium hydroxide (0.306 g, 5.45 mmol) in 10 mL of DMSO. The tube was sealed and heated to 95° C. for 16 hours, then allowed to cool to ambient temperature. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Column chromatography (10% MeOH/DCM/0.5% NH4OH) followed by trituration with methyl t-butyl ether afforded 42 mgs (6%) of the title compound. MS (APCI), positive scan, m/z=595.1 (M+H).

Workup

  1. customThe tube was sealed
  2. temperatureto cool to ambient temperature
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-57130f0057ef4c96b4bc1f5c366743f3
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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