Potassium Carbonate → 1-((S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone

HRID 1051665Notes

Reaction equation

HRID 1051665 reaction equation
Br[C:2]1[C:3]([O:16][C:17]2[N:25]=[C:24]3[C:20]([N:21]([CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][O:27]4)[CH:22]=[N:23]3)=[CH:19][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.C(=O)([O-])[O-].[K+].[K+].[CH:38]1([N:41]2[CH:45]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:43]=[N:42]2)[CH2:40][CH2:39]1.O1CCOCC1>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].O>[CH:38]1([N:41]2[CH:45]=[C:44]([C:2]3[C:3]([O:16][C:17]4[N:25]=[C:24]5[C:20]([N:21]([CH:26]6[CH2:31][CH2:30][CH2:29][CH2:28][O:27]6)[CH:22]=[N:23]5)=[CH:19][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:43]=[N:42]2)[CH2:40][CH2:39]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 593271331-Cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 1180864081-((S)-6-bromo-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone

Product 1

HCID 1180764371-((S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanoneYield 71.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL, round-bottom flask was charged with 1-((S)-6-bromo-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.200 g, 0.41 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.030 g, 0.04 mmol), potassium carbonate (0.170 g, 1.23 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.288 g, 1.23 mmol), 1,4-dioxane (20 mL), and water (2 mL). The resulting mixture stirred overnight at 100° C. After cooling to room temperature, the reaction mixture was passed through a short pad of Celite, and the filtrate was concentrated under vacuum. The residue was purified by preparative thin layer chromatography (eluting with 1:2, ethyl acetate/petroleum ether) to afford 1-((S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.150 g, 71%) as light yellow oil. MS (ESI, pos. ion) m/z 514 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe filtrate was concentrated under vacuum
  3. customThe residue was purified by preparative thin layer chromatography (eluting with 1:2, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-cec04c4b7b9b4bc68abe6e4e0b91fc0a
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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