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

HRID 1423342Notes

Reaction equation

HRID 1423342 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)C12 (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-473c6e0ef131424685fab50f946fb556
Source dataset
uspto-grants-2015_01
Patent number
US08927582B2

Reaction notes

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