Tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate → tert-Butyl 4-(2-(3-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-ylcarbamoyl)imidazo[1,2-a]pyridin-7-yloxy)ethyl)piperazine-1-carboxylate

HRID 706619Notes

Reaction equation

HRID 706619 reaction equation
CC(C)([O-])C.[K+].[OH:7][CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1.[CH3:23][C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][C:31]=2[NH:33][C:34]([C:36]2[N:40]3[CH:41]=[CH:42][C:43](F)=[CH:44][C:39]3=[N:38][CH:37]=2)=[O:35])[N:26]([CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[C:49]([CH3:53])[N:48]=2)[N:25]=1>C(O)(C)(C)C>[CH3:23][C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][C:31]=2[NH:33][C:34]([C:36]2[N:40]3[CH:41]=[CH:42][C:43]([O:7][CH2:8][CH2:9][N:10]4[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]4)=[CH:44][C:39]3=[N:38][CH:37]=2)=[O:35])[N:26]([CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[C:49]([CH3:53])[N:48]=2)[N:25]=1

Participants

5

Reactant 3

HCID 735736Tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 573866457-fluoro-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 57386649tert-Butyl 4-(2-(3-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-ylcarbamoyl)imidazo[1,2-a]pyridin-7-yloxy)ethyl)piperazine-1-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
60 °C

Procedure

A flask was charged with solid potassium tert-butoxide (0.07 g, 0.64 mmol), tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (0.17 g, 0.74 mmol), and tert-butanol (0.6 mL). The mixture was heated to 60° C. for 20 minutes before adding N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-fluoroimidazo[1,2-a]pyridine-3-carboxamide (0.045 g, 0.105 mmol) in one portion. The mixture was heated in a sand bath at 80° C. with stirring overnight. The reaction mixture was quenched with water and concentrated before purifying by reverse phase chromatography on a Biotage 25+C18 column, eluting with a gradient from 0-65% acetonitrile/water over 12 column volumes, to give tert-butyl 4-(2-(3-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-ylcarbamoyl)imidazo[1,2-a]pyridin-7-yloxy)ethyl)piperazine-1-carboxylate (40 mg) as a beige solid. MS (APCI), positive scan, m/z=639.1 (M+).

Workup

  1. temperatureThe mixture was heated in a sand bath at 80° C.
  2. customThe reaction mixture was quenched with water
  3. concentrationconcentrated
  4. custombefore purifying by reverse phase chromatography on a Biotage 25+C18 column
  5. washeluting with a gradient from 0-65% acetonitrile/water over 12 column volumes

Sources & evidence

ORD record
ord-dd712fa4aad540678c0a59cbbc689ddb
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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