Toluene → US10251893, Cpd 197

HRID 1036268Notes

Reaction equation

HRID 1036268 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:30])[CH2:18][C:19]3[CH:20]=[N:21][C:22](Cl)=[C:23]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:24]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:31][C:32]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[CH:34][N:33]=1.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C.O>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:30])[CH2:18][C:19]3[CH:24]=[C:23]([S:25]([CH3:28])(=[O:27])=[O:26])[C:22]([C:36]4[CH:35]=[CH:34][N:33]=[C:32]([CH3:31])[CH:37]=4)=[N:21][CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 164142742-Methylpyridine-4-boronic acid pinacol esterHCID 86657957N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(6-chloro-5-(methylsulfonyl)pyridin-3-yl)acetamide

Product 1

HCID 58447656US10251893, Cpd 197

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a sealed tube were added N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(6-chloro-5-(methylsulfonyl)pyridin-3-yl)acetamide 197-7 (30 mg, 0.07 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine 183-2 (22 mg, 0.10 mmol), Pd(PPh3)4 (4 mg, 0.003 mmol), Na2CO3 (22 mg, 0.20 mmol), Toluene (0.4 mL), H2O (0.4 mL) and ethanol (0.1 mL). The reaction mixture was stirred at 100° C. overnight. After cooling to room temperature, the solvents were removed by rotary evaporation. The crude product was purified by reverse phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2′-methyl-3-(methylsulfonyl)-2,4′-bipyridin-5-yl)acetamide 197. MS m/z 509.2 (M+1); 1H NMR 400 MHz (MeOD) δ 8.81 (d, 1H), 8.52 (d, 1H), 8.49 (d, 1H), 7.97 (s, 1H), 7.87 (d, 1H), 7.47 (s, 1H) 7.41 (dd, 1H), 7.37 (dd, 1H), 3.95 (s, 2H), 3.68 (t, 2H), 3.63 (t, 2H), 3.15 (t, 2H), 3.09 (t, 2H), 2.92 (s, 3H), 2.57 (s, 3H), 2.09 (s, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvents were removed by rotary evaporation
  3. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d85d2abfb4d74d20bb43ea46aa6e49da
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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