Cesium carbonate → N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl]methyl}-2-naphthamide

HRID 335052Notes

Reaction equation

HRID 335052 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([O:19][CH3:20])=[C:11]([C:21]([NH:23][C@H:24]3[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]3[OH:30])=[O:22])[CH:10]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:37][N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1>C1COCC1.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>[OH:30][C@H:25]1[CH2:26][CH2:27][CH2:28][CH2:29][C@@H:24]1[NH:23][C:21]([C:11]1[CH:10]=[C:9]([CH2:8][C:5]2[CH:6]=[N:7][C:2]([C:41]3[CH:40]=[N:39][N:38]([CH3:37])[CH:42]=3)=[CH:3][CH:4]=2)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]=1[O:19][CH3:20])=[O:22]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 547556014-[(6-Chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-1-methoxy-2-naphthamide

Product 1

HCID 54589421N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl]methyl}-2-naphthamide

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-1-methoxy-2-naphthamide (Example 3, 0.050 g, 0.12 mmol) in 3 mL of THF under an atmosphere of nitrogen was added aqueous cesium carbonate (1 M, 0.24 mL, 0.24 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.037 g, 0.18 mmol), and bis(tri-tert-butylphosphine)palladium(0) (4.0 mg, 0.0078 mmol). The reaction was heated at 100° C. for 16 hours, cooled to room temperature, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 470.9 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.59 (s, 1H), 8.26-8.23 (m, 1H), 8.12 (d, J=7.1 Hz, 1H), 8.07-7.89 (m, 3H), 7.85-7.82 (m, 1H), 7.70-7.61 (m, 3H), 4.52 (s, 2H), 4.04 (s, 3H), 4.00 (s, 3H), 3.98 (br s, 1H), 3.57-3.51 (m, 1H), 2.16-2.13 (m, 2H), 1.79 (br s, 2H), 1.50-1.21 (m, 4H).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified via preparative reverse phase HPLC

Sources & evidence

ORD record
ord-dcabfb6c34cc46c5822e833e18602af1
Source dataset
uspto-grants-2014_11
Patent number
US08883850B2

Reaction notes

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