Carbonic Acid → N-(4-(3,3'-Bipyridin-2-yloxy)phenyl)pyridin-2-amine

HRID 473628Notes

Reaction equation

HRID 473628 reaction equation
Cl.Br[C:3]1[C:4]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)=[CH:12][CH:11]=2)=[N:5][CH:6]=[CH:7][CH:8]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[CH:24]=1.C(O)(O)=O.COCCOC>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.CCO.O>[N:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:25]2[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=2)[C:4]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 767Carbonic AcidHCID 80711,2-DimethoxyethaneHCID 27343783-Pyridinylboronic acidHCID 67425919N-(4-(3-Bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride

Product 1

HCID 59374149N-(4-(3,3'-Bipyridin-2-yloxy)phenyl)pyridin-2-amine

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
145 °C

Procedure

A mixture of N-(4-(3-Bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride (0.257 g, 0.68 mmol), 3-pyridineboronic acid (0.115 g, 0.94 mmol), sodium carbonate anhydrous (0.358 g, 3.4 mmol) and trans-dichlorobis(triphenylphosphine)palladium (II) (0.045 g, 0.064 mmol) in 6:3:2 DME:H2O:EtOH was sealed under argon in a microwave tube and heated at 145° C. for 15 min in the microwave (Emrys by Personal Chemistry). The reaction was filtered and the filtrate was partitioned between EtOAc/brine. The aqueous layer was extracted with EtOAc (3×) and the combined organic layers were evaporated onto silica gel and purified by flash chromatography [Isco, (40 gram)] eluting with 2M NH3 in MeOH:CH2Cl2 (0:1→3:97) to give a white amorphous solid. MS (ESI, pos. ion) m/z: 341.1 [M+1]. IC50 (uM) 0.002612.

Workup

  1. filtrationThe reaction was filtered
  2. customthe filtrate was partitioned between EtOAc/brine
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. customthe combined organic layers were evaporated onto silica gel
  5. custompurified by flash chromatography [Isco, (40 gram)]
  6. washeluting with 2M NH3 in MeOH:CH2Cl2 (0:1→3:97)
  7. customto give a white amorphous solid

Sources & evidence

ORD record
ord-74a5c48dd805440b8d4cf71c8aa41651
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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