Potassium Carbonate → N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)-3,4'-bipyridine-2'-carboxamide

HRID 2091624Notes

Reaction equation

HRID 2091624 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:15]=[C:14]([C:16]3[N:20]([CH:21]4[CH2:23][CH2:22]4)[CH:19]=[N:18][N:17]=3)[S:13][CH:12]=2)=[O:9])[CH:3]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[C:26](B(O)O)[CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH:21]1([N:20]2[CH:19]=[N:18][N:17]=[C:16]2[C:14]2[S:13][CH:12]=[C:11]([NH:10][C:8]([C:4]3[CH:3]=[C:2]([C:26]4[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=4)[CH:7]=[CH:6][N:5]=3)=[O:9])[CH:15]=2)[CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 580356474-bromo-N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)picolinamide

Product 1

HCID 56597124N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)-3,4'-bipyridine-2'-carboxamideYield 20.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 4-bromo-N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)picolinamide (55 mg, 0.14 mmol), 3-pyridine boronic acid (17 mg, 0.14 mmol), dppf(Pd)Cl2 (5.2 mg, 0.0071 mmol), potassium carbonate (49 mg, 0.35 mmol) in degassed toluene (0.70 mL), degassed water (0.35 mL) and degassed ethanol (0.35 mL) was heated at 90° C. for 3 hours. The aqueous layer was separated, the organic layer was concentrated under reduced pressure, and the residue was purified by reverse-phase HPLC to give N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)-3,4′-bipyridine-2′-carboxamide as a white powder (11 mg, 20% yield). N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)-3,4′-bipyridine-2′-carboxamide; C20H16N6OS. 389.2 (M+1). 1H NMR (DMSO) δ 11.45 (s, 1H), 9.11 (d, J=2 Hz, 1H), 8.85 (d, J=5 Hz, 1H), 8.70-8.74 (m, 1H), 8.60 (s, 1H), 8.49 (s, 1H), 8.31-8.36 (m, 2H), 8.10 (dd, J=2, 5 Hz, 1H), 8.06 (s, 1H), 7.60 (dd, J=5, 8 Hz, 1H), 3.56-3.59 (m, 1H), 1.11-1.27 (m, 4H).

Workup

  1. customdegassed water (0.35 mL)
  2. customdegassed ethanol (0.35 mL)
  3. customThe aqueous layer was separated
  4. concentrationthe organic layer was concentrated under reduced pressure
  5. customthe residue was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-08176c435127479c9f9ed36b090591ef
Source dataset
uspto-grants-2013_05
Patent number
US08440665B2

Reaction notes

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