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 706598Notes

Reaction equation

HRID 706598 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.F[C:24]1[CH:29]=[CH:28][N:27]2[C:30]([C:33]([NH:35][C:36]3[CH:44]=[CH:43][CH:42]=[C:41]4[C:37]=3[C:38]([CH3:53])=[N:39][N:40]4[CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[C:48]([CH3:52])[N:47]=3)=[O:34])=[CH:31][N:32]=[C:26]2[CH:25]=1>C1COCC1.CN1C(=O)CCC1>[CH3:53][C:38]1[C:37]2[C:41](=[CH:42][CH:43]=[CH:44][C:36]=2[NH:35][C:33]([C:30]2[N:27]3[CH:28]=[CH:29][C:24]([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:25][C:26]3=[N:32][CH:31]=2)=[O:34])[N:40]([CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([CH3:52])[N:47]=2)[N:39]=1

Participants

6

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-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a 0.4 M solution of potassium tert-butoxide (0.068 g, 0.606 mmol) in THF cooled in an ice-water bath was added tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate 0.278 g, 1.21 mmol). The reaction was stirred for 10 minutes before adding 7-fluoro-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (Example 53; 0.100 g 0.241 mmol) in 2 mL of NMP. The reaction was warmed to ambient temperature and stirred for 1 hour, then heated to 60° C. and stirred for 12 hours. THF was removed by rotary evaporation and the mixture was heated to 120° C. for 5 hours. Another equivalent of potassium t-butoxide was added and the mixture was heated for another 3 hours. The reaction was quenched with water and extracted with EtOAc. The extracts were dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative thin layer chromatography and reverse phase chromatography gave the title compound. MS (APCI), positive scan, m/z=625.0 (M+H).

Workup

  1. stirringstirred for 1 hour
  2. temperatureheated to 60° C.
  3. stirringstirred for 12 hours
  4. customTHF was removed by rotary evaporation
  5. temperaturethe mixture was heated to 120° C. for 5 hours
  6. additionAnother equivalent of potassium t-butoxide was added
  7. temperaturethe mixture was heated for another 3 hours
  8. customThe reaction was quenched with water
  9. extractionextracted with EtOAc
  10. dry with materialThe extracts were dried over sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customPurification by preparative thin layer chromatography

Sources & evidence

ORD record
ord-cda1a7285a8545039e92663c375f9e72
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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