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

HRID 924005Notes

Reaction equation

HRID 924005 reaction equation
Br[C:2]1[C:3]([NH:22][CH2:23][CH2:24][CH2:25][OH:26])=[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].[CH3:27][C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>COCCOC.O>[OH:26][CH2:25][CH2:24][CH2:23][NH:22][C:3]1[C:2]([C:31]2[CH:32]=[N:33][C:28]([CH3:27])=[CH:29][CH:30]=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 899067795-bromo-6-((3-hydroxypropyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 1181953812-((3-Hydroxypropyl)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)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 161.1, 72 mg, 0.15 mmol), (6-methylpyridin-3-yl)boronic acid (20.7 mg, 0.15 mmol) and Na2CO3 (48 mg, 0.450 mmol) in a mixture of DME (3.2 mL), EtOH (0.43 mL) and water (0.64 mL) was flushed with argon for 5 min. Pd(PPh3)2Cl2 was added (5.3 mg, 0.0075 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 to afford the title compound. UPLC-MS (Condition 8) tR=1.87 min, m/z=447.1 [M+H]+, m/z=445.2 [M−H]−.

Workup

  1. customwas flushed with argon for 5 min
  2. additionPd(PPh3)2Cl2 was added (5.3 mg, 0.0075 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

Sources & evidence

ORD record
ord-72be4c5850a64419bb3a3bbb636f49dd
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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