Nitrogen → HCID 57863450, compound

HRID 1446763Notes

Reaction equation

HRID 1446763 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:15]=[CH:14][N:13]=2)=[O:10])=[C:4]([F:22])[CH:3]=1.[CH3:23][C:24]1[N:29]=[C:28]([C:30]2[CH:35]=[CH:34][N:33]3[CH:36]=[CH:37][N:38]=[C:32]3[CH:31]=2)[CH:27]=[CH:26][CH:25]=1.CC([O-])=O.[K+].N#N>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O>[C:18]([C:16]1[CH:15]=[CH:14][N:13]=[C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([C:36]3[N:33]4[CH:34]=[CH:35][C:30]([C:28]5[CH:27]=[CH:26][CH:25]=[C:24]([CH3:23])[N:29]=5)=[CH:31][C:32]4=[N:38][CH:37]=3)=[CH:3][C:4]=2[F:22])[CH:17]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 947Nitrogen2×HCID 517044Potassium AcetateHCID 57833783HCID 57833783, compoundHCID 68544792HCID 68544792, compound

Product 1

HCID 57863450HCID 57863450, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

In a stirred septum capped vial, charge 2-(4-bromo-2-fluoro-phenyl)-N-(4-tert-butyl-pyridin-2-yl)-acetamide (400 mg, 1.09 mmol), 7-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine (228 mg, 1.09 mmol), KOAc (213 mg, 2.18 mmol), PdCl2(PPh3)2 and flushes with N2 needle for 15 minutes then one adds DMSO (5 mL) and de-oxygenate with N2 needle and places vial in oil bath at 80 to 90° C. for 24 hours. Cool the reaction then purify by passing through Varian SCX® (10 g) column that is pre-washed with water and methanol, the product being eluted with (20%) 2 N NH3 in methanol/(80%) DCM. Evaporate solvent from the product containing fractions under reduced pressure. Chromatograph using (40 g ISCO®) SiO2 eluting with a gradient of 0% to 10% 2 M NH3 in MeOH with the balance DCM. Evaporate solvents and purify by reverse phase chromatography (C-18 acetonitrile/H2O with 0.1% TFA) Neutralize, extract, and strip off solvents. Dry in vacuum oven to afford 118.4 mg (21.9%) MS(ES), m/z 494 (M+1).

Workup

  1. customIn a stirred septum capped vial
  2. temperatureCool
  3. customthe reaction
  4. customthen purify
  5. washis pre-washed with water and methanol
  6. washthe product being eluted with (20%) 2 N NH3 in methanol/(80%) DCM
  7. additionEvaporate solvent from the product containing fractions under reduced pressure
  8. customEvaporate solvents and purify by reverse phase chromatography (C-18 acetonitrile/H2O with 0.1% TFA) Neutralize
  9. extractionextract
  10. customDry in vacuum oven
  11. customto afford 118.4 mg (21.9%) MS(ES), m/z 494 (M+1)

Sources & evidence

ORD record
ord-6b4ae1b4b34246cd93fe5bfb71ba348f
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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