Potassium Carbonate → USRE48711, Example 72

HRID 1040253Notes

Reaction equation

HRID 1040253 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[N:21]([CH:22]4[CH2:24][CH2:23]4)[CH:20]=[N:19][CH:18]=3)[CH:12]=2)=[O:9])[CH:3]=1.B(O)O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH:22]1([N:21]2[C:17]([C:13]3[CH:12]=[C:11]([NH:10][C:8]([C:4]4[CH:3]=[C:2]([C:3]5[CH:4]=[N:5][CH:6]=[CH:7][CH:2]=5)[CH:7]=[CH:6][N:5]=4)=[O:9])[CH:16]=[CH:15][CH:14]=3)=[CH:18][N:19]=[CH:20]2)[CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 581030874-bromo-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide

Product 1

HCID 58103045USRE48711, Example 72Yield 46.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

A suspension of 4-bromo-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide (75.0 mg, 0.196 mmol), boronic acid (33.8 mg, 0.274 mmol), dppf(Pd)Cl2 (14.3 mg, 0.0196), potassium carbonate (81.3 mg, 0.588 mmol) in degassed toluene (1 mL), degassed water (0.5 mL) and degassed isopropanol (0.5 mL) was heated at 95° C. for 2 hours. The aqueous phase was discarded and the solvent removed under reduced pressure from the organic portion. Purification by reverse phase HPLC provided N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-3,4′-bipyridine-2′-carboxamide (17.3 mg, 23%) as a white solid.

Workup

  1. customdegassed water (0.5 mL)
  2. customdegassed isopropanol (0.5 mL)
  3. customthe solvent removed under reduced pressure from the organic portion
  4. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-317ef1eb46bf49009288579b36e4859a
Source dataset
uspto-grants-2013_10
Patent number
US08552196B2

Reaction notes

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