Ethanol → 2-(4-Methyl-1,4-diazepan-1-yl)-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

HRID 923981Notes

Reaction equation

HRID 923981 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:28][CH2:27][CH2:26][N:25]([CH3:29])[CH2:24][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].[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>[CH3:29][N:25]1[CH2:26][CH2:27][CH2:28][N:22]([C:3]2[C:2]([C:32]3[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23][CH2:24]1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 899068165-bromo-6-(4-methyl-1,4-diazepan-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 1181952212-(4-Methyl-1,4-diazepan-1-yl)-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 5-bromo-6-(4-methyl-1,4-diazepan-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 146.1, 74 mg, 0.150 mmol), pyridin-3-ylboronic acid (18.5 mg, 0.150 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. Pd(PPh3)2Cl2 (5.3 mg, 0.0075 mmol) was added and the mixture was subjected to MW irradiation at 125° C. for 30 min. The RM was evaporated to dryness under reduced pressure and the residue 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=1.71 min, m/z=472.1 [M+H]+, m/z=470.2 [M−H]−.

Workup

  1. customwas flushed with argon
  2. customthe mixture was subjected to MW irradiation at 125° C. for 30 min
  3. customThe RM was evaporated to dryness under reduced pressure
  4. customthe residue was triturated with THF
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness under reduced pressure
  7. customthe crude product was purified by preparative LC-MS
  8. customTFA was removed

Sources & evidence

ORD record
ord-1fcecdf2a92c4b63b5b55686e1a0de39
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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