Ethanol → 2-((3-Hydroxypropyl)(methyl)amino)-6'-methyl-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

HRID 924010Notes

Reaction equation

HRID 924010 reaction equation
Br[C:2]1[C:3]([N:22]([CH2:24][CH2:25][CH2:26][OH:27])[CH3:23])=[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].[CH3:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>COCCOC.O>[OH:27][CH2:26][CH2:25][CH2:24][N:22]([CH3:23])[C:3]1[C:2]([C:32]2[CH:33]=[N:34][C:29]([CH3:28])=[CH:30][CH:31]=2)=[CH:21][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)=[O:8])=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 899063685-bromo-6-((3-hydroxypropyl)(methyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 1181953802-((3-Hydroxypropyl)(methyl)amino)-6'-methyl-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 5-bromo-6-((3-hydroxypropyl)(methyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 165.1, 92 mg, 0.189 mmol), (6-methylpyridin-3-yl)boronic acid (25.9 mg, 0.189 mmol) and Na2CO3 (60 mg, 0.566 mmol) in a mixture of DME (4.0 mL), EtOH (0.54 mL) and water (0.80 mL) was flushed with argon for 5 min. Pd(PPh3)2Cl2 was added (6.6 mg, 0.0094 mmol) and the mixture subjected to MW irradiation at 125° C. for 20 min. The vial was cooled to RT and the RM was evaporated to dryness under reduced pressure to give a residue that was triturated with THF and filtered. The filtrate was evaporated to dryness under reduced pressure and the crude product was purified by preparative LC-MS. TFA was removed using a SPE PL-HCO3 (StratoSpheres™ VariPure IPE) cartridge. Additional purification (Isolute Flash Silica gel cartridge, 5 g, elution of impurities with EtOAc, subsequent elution of product with MeOH) afforded the title compound. LC-MS (Condition 5) tR=1.65 min, m/z=461.2 [M+H]+, m/z=459.2 [M−H]−.

Workup

  1. customwas flushed with argon for 5 min
  2. additionPd(PPh3)2Cl2 was added (6.6 mg, 0.0094 mmol)
  3. customthe mixture subjected to MW irradiation at 125° C. for 20 min
  4. customthe RM was evaporated to dryness under reduced pressure
  5. customto give a residue that
  6. customwas triturated with THF
  7. filtrationfiltered
  8. customThe filtrate was evaporated to dryness under reduced pressure
  9. customthe crude product was purified by preparative LC-MS
  10. customTFA was removed
  11. customAdditional purification (Isolute Flash Silica gel cartridge, 5 g, elution of impurities with EtOAc, subsequent elution of product with MeOH)

Sources & evidence

ORD record
ord-418513f4bc2f4fa2801da92ed563eb32
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

Loading…