Sodium Carbonate → (R)-2'-Fluoro-2-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

HRID 923864Notes

Reaction equation

HRID 923864 reaction equation
Cl[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[F:28][C:29]1[C:34](B(O)O)=[CH:33][CH:32]=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[F:28][C:29]1[C:34]([C:2]2[C:3]([N:22]3[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]3)=[N:4][CH:5]=[C:6]([C:7]([NH:9][C:10]3[CH:11]=[CH:12][C:13]([O:16][C:17]([F:19])([F:20])[F:18])=[CH:14][CH:15]=3)=[O:8])[CH:21]=2)=[CH:33][CH:32]=[CH:31][N:30]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 89907107(R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 118195372(R)-2'-Fluoro-2-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of (R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 38.1, 50 mg, 0.124 mmol), (2-fluoropyridin-3-yl)boronic acid (26 mg, 0.187 mmol), 2 M Na2CO3 (0.124 mL, 0.249 mmol) and DME (2.5 mL) was flushed with argon. PdCl2(dppf)(CH2Cl2) (10 mg, 0.012 mmol) was added and the mixture was subjected to MW irradiation 140° C. for 30 min, filtered through a PL-Thiol MP SPE cartridge (StratoSpheres™, 6 mL), the cartridge was washed with MeOH and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative LC-MS to afford the title compound. LC-MS (Condition 6) tR=1.71 min, m/z=463.0 [M+H]+.

Workup

  1. customwas flushed with argon
  2. customthe mixture was subjected to MW irradiation 140° C. for 30 min
  3. filtrationfiltered through a PL-Thiol MP SPE cartridge (StratoSpheres™, 6 mL)
  4. washthe cartridge was washed with MeOH
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by preparative LC-MS

Sources & evidence

ORD record
ord-27ef97cc21f14567a72f455b3ca2204b
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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