Tetrahydrofuran → 4-(2-Naphthylmethyl)-2-pyridazin-4-yl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrile

HRID 2402073Notes

Reaction equation

HRID 2402073 reaction equation
Br[C:2]1[C:3]([C:24]#[N:25])=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[N:20][CH:19]=2)[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:8]=1.[Br-].[CH:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29][C:28]=1[CH2:37][Zn+].O1CCCC1>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29][C:28]=1[CH2:37][C:2]1[C:3]([C:24]#[N:25])=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[N:20][CH:19]=2)[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:8]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 667492984-Bromo-2-pyridazin-4-yl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrileHCID 178419770HCID 178419770, compound

Product 1

HCID 667490584-(2-Naphthylmethyl)-2-pyridazin-4-yl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrileYield 72%

Reagents, catalysts & solvents 1

HCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
70 °C

Procedure

Bis(tri-t-butylphosphine)palladium(0) (4.92 mg, 0.00963 mmol), 4-bromo-2-pyridazin-4-yl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrile (0.0402 g, 0.0963 mmol), 2-naphthylmethylzinc bromide in tetrahydrofuran (0.50M, 0.578 mL, 0.289 mmol) and tetrahydrofuran (4.0 mL, 49 mmol) were added to a microwave tube. The tube was sealed under a nitrogen atmosphere and heated at 70° C. for 2 h then cooled to rt. The mixture was concentrated in vacuo and the residue was purified by chromatography on a silica gel column eluting with 0-100% EtOAc in hexane to afford a solid product (0.0332 g, yield 72%). LCMS: (AA) ES+, 479. 1H NMR (300 MHz, d4-methanol) δ: 9.63 (s, 1H), 9.28-9.35 (m, 1H), 8.68 (s, 1H), 8.13-8.15 (m, 1H), 7.69-8.00 (m, 4H), 7.37-7.48 (m, 3H), 5.62-5.66 (m, 1H), 3.94-4.08 (m, 1H), 3.69-3.80 (m, 1H), 3.30 (s, 2H), 2.07-2.22 (m, 1H), 1.95-2.07 (m, 2H), 1.61-1.79 (m, 3H).

Workup

  1. customThe tube was sealed under a nitrogen atmosphere
  2. temperaturethen cooled to rt
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was purified by chromatography on a silica gel column
  5. washeluting with 0-100% EtOAc in hexane

Sources & evidence

ORD record
ord-850db955030d472baeabf1e881b00d80
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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