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

HRID 924011Notes

Reaction equation

HRID 924011 reaction equation
Br[C:2]1[C:3]([N:22]([CH2:24][CH2:25][CH2:26][N:27]([CH3:29])[CH3:28])[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].[N:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>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.O>[CH3:28][N:27]([CH3:29])[CH2:26][CH2:25][CH2:24][N:22]([CH3:23])[C:3]1[C:2]([C:32]2[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=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

8

Reactant 4

HCID 702EthanolHCID 10340Sodium Carbonate2×HCID 27343783-Pyridinylboronic acid2×HCID 899066305-bromo-6-((3-(dimethylamino)propyl)(methyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 1181953422-((3-(Dimethylamino)propyl)(methyl)amino)-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 5-bromo-6-((3-(dimethylamino)propyl)(methyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 165.1, 88 mg, 0.185 mmol), pyridin-3-ylboronic acid (22.7 mg, 0.185 mmol) and Na2CO3 (59 mg, 0.555 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 (6.5 mg, 0.0093 mmol) and the mixture was subjected to MW irradiation at 125° C. (MW irradiation) for 30 min. Additional pyridin-3-ylboronic acid (22.7 mg, 0.185 mmol), Na2CO3 (59 mg, 0.555 mmol) and Pd(PPh3)2Cl2 (6.5 mg, 0.0093 mmol) were added and the mixture stirred at 125° C. for further 30 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. LC-MS (Condition 6) tR=1.33 min, m/z=474.0 [M+H]+.

Workup

  1. customwas flushed with argon for 5 min
  2. additionPd(PPh3)2Cl2 was added (6.5 mg, 0.0093 mmol)
  3. customthe mixture was subjected to MW irradiation at 125° C.
  4. custom(MW irradiation) for 30 min
  5. temperatureThe vial was cooled to RT
  6. customthe RM was evaporated to dryness under reduced pressure
  7. customto give a residue that
  8. customwas triturated with THF
  9. filtrationfiltered
  10. customThe filtrate was evaporated to dryness under reduced pressure
  11. customthe crude product was purified by preparative LC-MS
  12. customTFA was removed

Sources & evidence

ORD record
ord-cf70ebf4f2a64db1ab8f2a1172682065
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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