Cesium carbonate → HCID 53236425, compound

HRID 407181Notes

Reaction equation

HRID 407181 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:10]=[C:11]([C:20]([NH:22][C@H:23]3[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]3[OH:29])=[O:21])[C:12](=[O:19])[N:13]3[C:18]=2[CH:17]=[CH:16][CH:15]=[CH:14]3)=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]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:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@@H:23]1[NH:22][C:20]([C:11]1[C:12](=[O:19])[N:13]2[C:18]([CH:17]=[CH:16][CH:15]=[CH:14]2)=[C:9]([CH2:8][C:5]2[CH:4]=[CH:3][C:2]([C:40]3[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=3)=[CH:7][N:6]=2)[CH:10]=1)=[O:21]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 53236423HCID 53236423, compound

Product 1

HCID 53236425HCID 53236425, compound

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-[(5-bromopyridin-2-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-4-oxo-4H-quinolizine-3-carboxamide (Example 2, 0.045 g, 0.099 mmol) in 2 mL of THF under an atmosphere of nitrogen was added aqueous cesium carbonate (1 N, 0.20 mL, 0.20 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.062 g, 0.30 mmol), and bis(tri-tert-butylphosphine)palladium(0) (5.0 mg, 0.010 mmol). The reaction was heated at 100° C. for 15 h, cooled to rt, and concentrated in vacuo. The resultant residue was subjected to purification via reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a high resolution mass spectrum (ES+) m/z of 472.2330 calculated for M+H+ [C27H30N5O3: 472.2343]: 1H NMR (400 MHz, CD3OD) δ 9.50 (d, J=7.0 Hz, 1H), 8.83 (s, 1H), 8.53-8.50 (m, 1H), 8.35-8.30 (m, 1H), 8.16 (s, 1H), 8.06-7.97 (m, 2H), 7.88 (d, J=8.0 Hz, 1H), 7.56 (d, J=8.2 Hz, 1H), 7.52-7.48 (m, 1H), 4.62 (s, 2H), 3.95 (s, 3H), 3.86-3.81 (m, 1H), 3.55-3.48 (m, 1H), 3.21-3.12 (m, 1H), 2.13-2.10 (m, 1H), 2.03-1.87 (m, 1H), 1.79-1.73 (m, 2H), 1.40-1.24 (m, 3H).

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated in vacuo
  3. customThe resultant residue was subjected to purification via reverse phase HPLC

Sources & evidence

ORD record
ord-6801d41810aa466ab190bd354233213e
Source dataset
uspto-grants-2014_06
Patent number
US08754220B2

Reaction notes

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