Cesium carbonate → HCID 118075783, compound

HRID 1051622Notes

Reaction equation

HRID 1051622 reaction equation
[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:25][C:26]4[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=4[C:28]#[N:29])[C:12](B4OC(C)(C)C(C)(C)O4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:34])=[O:5])[CH2:3][CH2:2]1.Br[C:36]1[N:37]=[N:38][N:39]([CH3:41])[CH:40]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:25][C:26]4[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=4[C:28]#[N:29])[C:12]([C:36]4[N:37]=[N:38][N:39]([CH3:41])[CH:40]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:34])=[O:5])[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 217664104-Bromo-1-methyl-1H-1,2,3-triazoleHCID 123794489HCID 123794489, compound

Product 1

HCID 118075783HCID 118075783, compoundYield 13.2%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-2-(1-(cyclopropanecarbonyl)-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-5-yloxy)benzonitrile (0.050 g, 0.11 mmol), 4-bromo-1-methyl-1H-1,2,3-triazole (0.025 g, 0.15 mmol), cesium carbonate (0.110 g, 0.34 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.10 g, 0.01 mmol) in 1,4-dioxane (10 mL) and water (3 mL) was stirred overnight at 80° C. The reaction mixture was cooled to room temperature and filtered through a short pad of Celite. The filtrate was concentrated and purified via preparative thin layer chromatography (eluting with 25% ethyl acetate-petroleum ether) to afford (S)-2-(1-(cyclopropanecarbonyl)-2-methyl-6-(1-methyl-1H-1,2,3-triazol-4-yl)-1,2,3,4-tetrahydroquinolin-5-yloxy)benzonitrile (0.006 g, 13%) as a white solid. MS (ESI, pos. ion) m/z 414 [M+H]+. 1H NMR (400 MHz, CD3OD) δ ppm 0.75-0.82 (m, 1H), 0.88-1.05 (m, 2H), 1.15-1.25 (m, 3H), 1.28-1.35 (m, 1H), 1.45-1.55 (m, 1H), 1.97-2.05 (m, 1H), 2.15-2.25 (m, 1H), 2.27-2.45 (m, 1H), 2.60-2.75 (m, 1H), 4.09 (s, 3H), 4.75-4.85 (m, 1H), 6.58 (d, J=8.40 Hz, 1H), 7.17 (t, J=8.00 Hz, 1H), 7.45-7.51 (m, 1H), 7.57 (d, J=8.40 Hz, 1H), 7.78 (d, J=1.20 Hz, 1H), 8.03-8.07 (m, 2H). MS (ESI, pos. ion) m/z 414 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through a short pad of Celite
  3. concentrationThe filtrate was concentrated
  4. custompurified via preparative thin layer chromatography (eluting with 25% ethyl acetate-petroleum ether)

Sources & evidence

ORD record
ord-fd57daae117e4a5b826282d7e266d27e
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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