Potassium Carbonate → HCID 67035493, compound

HRID 524371Notes

Reaction equation

HRID 524371 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[CH3:13][CH2:14][N:15](C(C)C)[CH:16](C)C.CC1(C)C(C)(C)OB([C:30]2[CH:35]=[CH:34][C:33]([NH2:36])=[CH:32][CH:31]=2)O1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+].[CH3:66][N:67]1[C:71](=O)[CH2:70][CH2:69][CH2:68]1>CC([O-])=O.CC([O-])=O.[Pd+2]>[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:8][CH2:9][N:10]([C:16]3[CH:66]=[N:67][C:71]4[C:14]([N:15]=3)=[CH:13][C:68]([C:30]3[CH:31]=[CH:32][C:33]([NH2:36])=[CH:34][CH:35]=3)=[CH:69][CH:70]=4)[CH2:11][CH2:12]2)=[CH:3][CH:2]=1

Participants

8

Reactant 6

HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 705171-(4-Pyridyl)piperazineHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 67035493HCID 67035493, compoundYield 125%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
160 °C

Procedure

To a stirred solution of 2.43 g (10 mmol) intermediate example 1.1 in NMP (45 mL) was added 3.26 g (20 mmol, 2 eq) 1-(4-pyridinyl)-piperazine, and 5.14 mL (3.89 g, 30 mmol, 3 eq) DIPEA at room temperature in a microwave reactor. The solution was heated at 160° C. for 60 min under microwave irradiation. After cooling, 3.28 g (15 mmol, 1.5 eq) 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-benzenamine, 0.22 g (1 mmol, 0.1 eq) Pd(OAc)2, 0.61 g (2 mmol, 0.2 eq) P(oTol)3 and 30 mL potassium carbonate solution (1M in H2O, 3 eq) were added. The solution was heated at 140° C. for 40 min under microwave irradiation. After cooling, the solution was filtered through Kieselgur and evaporated. The residue was dissolved in MeOH/DCM 1:1 and filtered through Kieselgur to give 4.79 g (125%, with residual NMP) 4-[3-(4-pyridin-4-yl-piperazin-1-yl)-quinoxalin-6-yl]-phenylamine: 1H-NMR (300 MHz, d6-DMSO): δ=8.74 (1H, s), 8.17 (2H, d), 7.78 (1H, d), 7.69 (1H, s), 7.63 (1H, d), 7.50 (2H, d), 6.87 (2H, d), 6.64 (2H, d), 5.33 (2H, bs), 3.89 (4H, tr), 3.51 (4H, tr) ppm; UPLC-MS: RT=0.67 min; m/z (ES+) 383.5 [MH+]; required MW=382.5.

Workup

  1. temperatureAfter cooling
  2. temperatureThe solution was heated at 140° C. for 40 min under microwave irradiation
  3. temperatureAfter cooling
  4. filtrationthe solution was filtered through Kieselgur
  5. customevaporated
  6. dissolutionThe residue was dissolved in MeOH/DCM 1:1
  7. filtrationfiltered through Kieselgur

Sources & evidence

ORD record
ord-0f816f663da24ab5b805ec1ad95f7616
Source dataset
uspto-grants-2016_05
Patent number
US09340528B2

Reaction notes

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