Potassium Carbonate → N-((2'-fluoro-[2,4'-bipyridin]-5-yl)methyl)-2-oxo-2H-[1,3'-bipyridine]-6'-carboxamide

HRID 711250Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH2:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([F:24])[CH:19]=3)=[N:16][CH:17]=2)=[O:9])=[N:6][CH:7]=1.[OH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[F:24][C:20]1[CH:19]=[C:18]([C:15]2[CH:14]=[CH:13][C:12]([CH2:11][NH:10][C:8]([C:5]3[N:6]=[CH:7][C:2]([N:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]4=[O:25])=[CH:3][CH:4]=3)=[O:9])=[CH:17][N:16]=2)[CH:23]=[CH:22][N:21]=1

Participants

Conditions

Temperature: 108 °C

Procedure

A mixture of 5-bromo-N-42′-fluoro-[2,4′-bipyridin]-5-yl)methyl)picolinamide 38-4 (38.6 mg, 0.1 mmol), 2-hydroxypyridine 44-1 (19.0 mg, 0.2 mmol), CuI (9.5 mg, 0.05 mmol), trans-N1,N2-dimethylcyclohexane-1,2-diamine (7.1 mg, 0.05 mmol) and K2CO3 (28 mg, 0.20 mmol) in toluene (0.6 mL) was stirred at 108° C. for 8 hours. After cooling to room temperature, the mixture was filtered through celite (washed with ethyl acetate) and the filtrate was concentrated with rotavap. The residue was subjected to preparative reverse phase HPLC separation to give N-42′-fluoro-[2,4′-bipyridin]-5-yl)methyl)-2-oxo-2H-[1,3′-bipyridine]-6′-carboxamide 44 as a solid.

Workup

temperatureAfter cooling to room temperature
filtrationthe mixture was filtered through celite (washed with ethyl acetate)
concentrationthe filtrate was concentrated with rotavap
customThe residue was subjected to preparative reverse phase HPLC separation

Sources & evidence

ORD record: ord-4175095b8e60402083459e4fcc7226c9
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181235B2

Reaction notes

Loading…