2-(Dicyclohexylphosphino)biphenyl → (R)-3-[6-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-pyridazin-3-yl]-9H-carbazole

HRID 1441441Notes

Reaction equation

HRID 1441441 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([O:8][C@@H:9]2[CH:14]3[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]3)[CH2:10]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[CH:27][C:28]3[NH:29][C:30]4[C:35]([C:36]=3[CH:37]=2)=[CH:34][CH:33]=[CH:32][CH:31]=4)O1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>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>[N:11]12[CH2:16][CH2:15][CH:14]([CH2:13][CH2:12]1)[C@@H:9]([O:8][C:5]1[N:6]=[N:7][C:2]([C:25]3[CH:26]=[CH:27][C:28]4[NH:29][C:30]5[C:35]([C:36]=4[CH:37]=3)=[CH:34][CH:33]=[CH:32][CH:31]=5)=[CH:3][CH:4]=1)[CH2:10]2

Participants

5

Reactant 3

HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 670701343-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)carbazoleHCID 86598842(3R)-3-[(6-chloropyridazin-3-yl)oxy]quinuclidine

Product 1

HCID 11372142(R)-3-[6-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-pyridazin-3-yl]-9H-carbazole

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

The product of Example 9A (0.173 g, 0.72 mmol) was coupled with the product of Example 38A (0.267 g, 0.91 mmol) under the catalysis of dichlorobis(triphenylphosphine)palladium(II) (Aldrich, 5.3 mg, 0.007 mmol) and 2-(dicyclohexylphosphino)biphenyl (Strem Chemicals, 7.3 mg, 0.021 mmol) at 150° C. for 10 min. according to the procedure of Example 29A. The title product was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10) (v. 40/60 to 70/30 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid. 1H NMR (300 MHz, CD3OD) δ 1.45-1.62 (m, 1H), 1.68-1.92 (m, 2H), 2.00-2.15 (m, 1H), 2.27-2.40 (m, Hz, 1H), 2.75-3.05 (m, 5H), 3.43-3.59 (m, Hz, 1H), 5.22-5.42 (m, Hz, 1H), 7.16-7.24 (m, 1H), 7.28 (d, J=9 Hz, 1H), 7.36-7.44 (m, 1H), 7.45-7.52 (m, 1H), 7.57 (d, J=8 Hz, 1H), 8.02 (dd, J=9, 2 Hz, 1H), 8.17 (t, J=9 Hz, 2H), 8.67 (s, 1H) ppm; MS (DCI/NH3) m/z 371 (M+H)+.

Workup

  1. customThe title product was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10) (v. 40/60 to 70/30 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid

Sources & evidence

ORD record
ord-1749d984873d4bb485b24f9d89b5c61b
Source dataset
uspto-grants-2010_02
Patent number
US07655657B2

Reaction notes

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