Potassium Carbonate → (S)-3-{4-[2-(4-Isopropyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester

HRID 2272838Notes

Reaction equation

HRID 2272838 reaction equation
Br[C:2]1[N:28]=[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][O:11][C:12]3[CH:17]=[CH:16][C:15]([C@@H:18]([C:25]#[C:26][CH3:27])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:14][CH:13]=3)=[CH:9][N:4]2[N:3]=1.[CH:29]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)([CH3:31])[CH3:30].C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:23]([O:22][C:20](=[O:21])[CH2:19][C@@H:18]([C:15]1[CH:16]=[CH:17][C:12]([O:11][CH2:10][C:8]2[CH:7]=[CH:6][C:5]3[N:4]([N:3]=[C:2]([C:35]4[CH:36]=[CH:37][C:32]([CH:29]([CH3:31])[CH3:30])=[CH:33][CH:34]=4)[N:28]=3)[CH:9]=2)=[CH:13][CH:14]=1)[C:25]#[C:26][CH3:27])[CH3:24]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27734804-Isopropylphenylboronic acidHCID 118151365Ethyl (3S)-3-[4-[(2-bromo-[1,2,4]triazolo[1,5-a]pyridin-6-yl)methoxy]phenyl]hex-4-ynoate

Product 1

HCID 118129995(S)-3-{4-[2-(4-Isopropyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl esterYield 68.75%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of ethyl (3S)-3-[4-[(2-bromo-[1,2,4]triazolo[1,5-a]pyridin-6-yl)methoxy]phenyl]hex-4-ynoate (0.3 g, 0.67 mmol) and 4-isopropyl-phenylboronic acid (0.24 g, 1.0 mmol) in toluene (16 mL) and EtOH (4 mL) is added 2 M K2CO3 (0.6 mL, 1.34 mmol). The mixture is purged with argon for 30 minutes. Pd(PPh3)4 (0.077 g, 0.067 mmol) is added and the mixture is heated at 100° C. overnight. The reaction mixture is cooled to room temperature, filtered through diatomaceous earth. The filtrate is diluted with water (30 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts are washed with saturated brine solution (20 mL), dried over sodium sulphate, filtered, and concentrated to dryness. The crude material is purified by silica gel chromatography (combiflash using 24 g redisep column) eluting with 45% EtOAc/hexane to give the title compound as a brown liquid (0.22 g, 68.75%). LCMS m/z 481 (M+H)+.

Workup

  1. customThe mixture is purged with argon for 30 minutes
  2. temperatureThe reaction mixture is cooled to room temperature
  3. filtrationfiltered through diatomaceous earth
  4. additionThe filtrate is diluted with water (30 mL)
  5. extractionextracted with EtOAc (2×20 mL)
  6. washThe combined organic extracts are washed with saturated brine solution (20 mL)
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude material is purified by silica gel chromatography (combiflash using 24 g redisep column)
  11. washeluting with 45% EtOAc/hexane

Sources & evidence

ORD record
ord-be096d51eeb24f83af32fb93eaa787d4
Source dataset
uspto-grants-2015_09
Patent number
US09120793B2

Reaction notes

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