Potassium Carbonate → HCID 46896613, compound

HRID 449956Notes

Reaction equation

HRID 449956 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3=[N:19][N:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])[C:21](=[O:22])[C:11]3=[N:10]2)=[CH:4][CH:3]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[N:10][N:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([C:34]4[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=4)=[CH:3][CH:4]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 468966115-[(6-Bromopyridin-3-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 46896613HCID 46896613, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

5-[(6-Bromopyridin-3-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 22) 74 mg, 0.17 mmol] was dissolved in dimethyl sulfoxide (1 mL) and treated with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (59 mg, 0.28 mmol, 1.7 equiv), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-iso-propylbiphenyl (X-PHOS, 36 mg, 0.076 mmol, 0.46 equiv), palladium(II)acetate (8.0 mg, 0.033 mmol, 0.2 equiv), and an aqueous solution (0.2 mL) of potassium carbonate (69 mg, 0.50 mmol, 3.0 equiv). The mixture was placed into an oil bath preheated at 80° C. for 30 minutes, cooled to ambient temperature, poured into water and extracted twice with ethyl acetate. The combined organic extracts were washed once with water and brine, dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 94:6; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.63 (1H, s), 8.31 (1H, d, J=7.5 Hz), 7.93 (1H, s), 7.91 (1H, s), 7.68-7.53 (4H, m), 7.47-7.41 (2H, m), 7.38-7.31 (3H, m), 5.84 (2H, s), 3.96 (3H, s), 2.38 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 448.1885 [(M+H)+; calculated for C26H22N7O: 448.1880].

Workup

  1. customThe mixture was placed into an oil bath
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic extracts were washed once with water and brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel gradient chromatography (100:0 to 94:6; chloroform:methanol)

Sources & evidence

ORD record
ord-11d6ddd668634beeb2ed2b613b445346
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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