Nitrogen → {4-[7-(4-Methanesulfonyl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-phenyl}-methanol

HRID 1446746Notes

Reaction equation

HRID 1446746 reaction equation
N#N.Cl[C:4]1[CH:9]=[CH:8][N:7]2[C:10]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][CH:14]=3)=[CH:11][N:12]=[C:6]2[CH:5]=1.[CH3:21][S:22]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)(=[O:24])=[O:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].CO.O1CCOCC1.O>[CH3:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([C:4]2[CH:9]=[CH:8][N:7]3[C:10]([C:13]4[CH:18]=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][CH:14]=4)=[CH:11][N:12]=[C:6]3[CH:5]=2)=[CH:27][CH:26]=1)(=[O:24])=[O:23]

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 68544639[4-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-phenyl]-methanol

Product 1

HCID 68542230{4-[7-(4-Methanesulfonyl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-phenyl}-methanolYield 100.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
65 °C

Procedure

Charge a 100 mL round bottom flask equipped with: a magnetic stirrer, temperature controlled heating mantle, N2 atmosphere, condenser, with [4-(7-chloro-imidazo[1,2-a]pyridin-3-yl)-phenyl]-methanol (1.11 g, 4.3 mmol), 4-(methylsulfonyl)-phenyl boronic acid (1.27 g, 6.4 mmol), 2-Dicyclohexyl-phosphino-2′,6′-dimethoxy-1,1′-biphenyl (236 mg), Pd(OAc)2 (60 mg), K3PO4 (3.6 g, 16.9 mmol), dioxane: H2O 2:1 (50 mL), EtOH-(3A) (5 mL). Warm the reaction while purging with a N2 needle, then heat to 65° C. for 18 hours. Cool the reaction to room temperature and siphon off the bottom layer (8 mL). Evaporate the reaction under vacuum and dissolve the residue into warm MeOH and filter to remove Pd (0) solids. Rinse the solids with warm MeOH and combine all the MeOHd. (total of 1 L). Evaporate the dissolved crude product under vacuum with 20 g of SiO2 to dryness then chromatograph using SiO2 eluting with a gradient of 0% to 10% of 2 M NH3 in MeOH with the balance CH2Cl2. Dry the product in a vacuum oven at 40° C. for 24 hours to give a yellow solid 1.64 g (100. %) suspect trapped solvent. MS (ES), m/z 379 (M+1).

Workup

  1. additionCharge a 100 mL round bottom flask
  2. customequipped with: a magnetic stirrer
  3. temperatureWarm
  4. customthe reaction
  5. customwhile purging with a N2 needle
  6. temperatureCool
  7. customthe reaction to room temperature
  8. customEvaporate
  9. customthe reaction under vacuum
  10. dissolutiondissolve the residue
  11. filtrationfilter
  12. customto remove Pd (0) solids
  13. washRinse the solids with warm MeOH
  14. customEvaporate the
  15. dissolutiondissolved crude product under vacuum with 20 g of SiO2 to dryness
  16. customDry the product in a vacuum oven at 40° C. for 24 hours

Sources & evidence

ORD record
ord-a567b05413bc4081b789ef181434bf44
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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