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

HRID 706561Notes

Reaction equation

HRID 706561 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([CH2:10][N:11]3[C:19]4[C:14](=[C:15]([NH:20][C:21]([C:23]5[N:27]6[CH:28]=[CH:29][C:30](F)=[CH:31][C:26]6=[N:25][CH:24]=5)=[O:22])[CH:16]=[CH:17][CH:18]=4)[C:13]([CH3:33])=[N:12]3)[CH:7]=[CH:6][CH:5]=2)[CH2:3][CH2:2]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.CC(C)([O-])C.[K+]>C(O)(C)(C)C.O>[CH:1]1([C:4]2[N:9]=[C:8]([CH2:10][N:11]3[C:19]4[C:14](=[C:15]([NH:20][C:21]([C:23]5[N:27]6[CH:28]=[CH:29][C:30]([O:44][CH2:43][CH2:42][N:37]7[CH2:38][CH2:39][N:40]([CH3:41])[C@@H:35]([CH3:34])[CH2:36]7)=[CH:31][C:26]6=[N:25][CH:24]=5)=[O:22])[CH:16]=[CH:17][CH:18]=4)[C:13]([CH3:33])=[N:12]3)[CH:7]=[CH:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 67975003(S)-2-(3,4-dimethylpiperazin-1-yl)ethanolHCID 67976126N-(1-((6-cyclopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)-7-fluoroimidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 57384859(S)-N-(1-((6-cyclopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)-7-(2-(3,4-dimethylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
95 °C

Procedure

N-(1-((6-cyclopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)-7-fluoroimidazo[1,2-a]pyridine-3-carboxamide (Example 16, Step G; 0.250 g, 0.568 mmol), (S)-2-(3,4-dimethylpiperazin-1-yl)ethanol (0.449 g, 2.84 mmol), and potassium t-butoxide (0.382 g, 3.41 mmol) were combined in t-butanol in a pressure tube. The tube was sealed and warmed 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 10% aqueous potassium carbonate, dried over sodium sulfate and concentrated under reduced pressure. Column chromatography (10% MeOH/DCM/0.5% NH4OH) of the crude material followed by trituration with ether gave 102 mg (31%) of the title compound. MS (APCI), positive scan, m/z=579.1 (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 10% aqueous potassium carbonate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-130557fd4d90448fa33026a631ec6d5d
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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