Cesium carbonate → HCID 118075401, compound

HRID 1051598Notes

Reaction equation

HRID 1051598 reaction equation
Br[C:2]1[C:3]([O:16][C:17]2[N:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][CH2:5]2.[CH:27]1([N:30]2[CH:34]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:32]=[N:31]2)[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CC(C1C=C(C(C)C)C(C2C=CC=C(P(C3CCCCC3)C3CCCCC3)C=2)=C(C(C)C)C=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+]>[CH:27]1([N:30]2[CH:34]=[C:33]([C:2]3[C:3]([O:16][C:17]4[N:26]=[CH:25][C:24]5[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=5)[N:18]=4)=[C:4]4[C:9](=[CH:10][CH:11]=3)[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][CH2:5]4)[CH:32]=[N:31]2)[CH2:29][CH2:28]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 593271331-Cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118086278HCID 118086278, compound

Product 1

HCID 118075401HCID 118075401, compoundYield 45%

Reagents, catalysts & solvents 3

HCID 72376365[2-(2-Aminophenyl)phenyl]-chloro-palladium dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphaneCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-1-(6-bromo-2-methyl-5-(quinazolin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.025 g, 0.061 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.017 g, 0.073 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl) palladium(II) (XPhos 2nd generation precatalyst) (2.4 mg, 0.003 mmol), and cesium carbonate (0.059 g, 0.182 mmol) in 1,4-dioxane (2.0 mL) and water (0.40 mL) was heated at 100° C. for 2 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 25-100% ethyl acetate-hexane) to afford (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(quinazolin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.012 g, 45%) as a white solid. MS (ESI, pos. ion) m/z 440. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.81-0.91 (m, 5H), 1.07 (d, J=6.74 Hz, 3H), 1.47 (m, 1H), 2.03 (br dd, J=13.34, 6.89 Hz, 1H), 2.18 (s, 3H), 2.44 (m, 1H), 3.55-3.67 (m, 1H), 4.63 (m, 1H), 7.41 (br s, 1H), 7.51-7.70 (m, 3H), 7.72 (s, 1H), 7.91 (ddd, J=8.50, 7.04, 1.47 Hz, 1H), 8.06 (s, 1H), 8.10 (d, J=8.21 Hz, 1H), 9.54 (s, 1H). MS (ESI, pos. ion) m/z 440 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationconcentrated
  3. customto afford an orange oil
  4. customThis material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 25-100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-25a21f0098384a2b85787ca05191b795
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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