Ethanol → HCID 68065989, compound

HRID 594946Notes

Reaction equation

HRID 594946 reaction equation
I[C:2]1[C:6]2[CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10][C:5]=2[N:4](C(OCC)=O)[N:3]=1.[N:23]1[CH:24]=[CH:25][N:26]2[CH:31]=[C:30](B(O)O)[CH:29]=[CH:28][C:27]=12.C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>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.O>[N:23]1[CH:24]=[CH:25][N:26]2[CH:31]=[C:30]([C:2]3[C:6]4[CH2:7][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:9][CH2:10][C:5]=4[NH:4][N:3]=3)[CH:29]=[CH:28][C:27]=12

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 103648605-tert-Butyl 1-ethyl 3-iodo-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-1,5(4H)-dicarboxylateHCID 44119340Imidazo[1,2-a]pyridin-6-ylboronic acid

Product 1

HCID 68065989HCID 68065989, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

5-Tert-butyl 1-ethyl 3-iodo-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-1,5(4H)-dicarboxylate (1 g, 0.002 mol), (synthesized from patent procedure: WO 2004014374 A1) was added to a vial containing imidazo[1,2-a]pyridin-6-ylboronic acid (0.577 g, 0.00356 mol) and tetrakis(triphenylphosphine)palladium (0.1372 g, 0.00011 mol). After purging the vial with nitrogen gas, dioxane: ethanol: water solution (7:3:2, 7.125 mL) and 2M sodium carbonate (0.007125 mol) was added to the vial respectively. The reaction mixture was stirred and was heated in the microwave at 160° C. for 20 min. Upon completion, the mixture was concentrated under vacuo. The residue was dissolved in ethyl acetate, and filtered through a fitted reservoir. The ethyl acetate layer was concentrated and columned using flash chromatography (0-100% ethyl acetate in hexane and 0-20% methanol in dichloromethane. The remaining residue that didn't dissolve in ethyl acetate was dissolved in methanol and filtered through a fritted reservoir. The methanol layer was concentrated and submitted for reverse phase prep. Pure product (quantitative yield) was recovered.

Workup

  1. additionwas added to
  2. customAfter purging the vial with nitrogen gas, dioxane
  3. concentrationUpon completion, the mixture was concentrated under vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. filtrationfiltered through a fitted reservoir
  6. concentrationThe ethyl acetate layer was concentrated
  7. dissolutionThe remaining residue that didn't dissolve in ethyl acetate
  8. dissolutionwas dissolved in methanol
  9. filtrationfiltered through a fritted reservoir
  10. concentrationThe methanol layer was concentrated

Sources & evidence

ORD record
ord-c9bca231b92d417299d21605fe2d1365
Source dataset
uspto-grants-2016_01
Patent number
US09242981B2

Reaction notes

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