Toluene → US10251893, Cpd 190

HRID 592209Notes

Reaction equation

HRID 592209 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:27])[CH2:18][C:19]3[CH:20]=[N:21][C:22](Cl)=[C:23]([F:25])[CH:24]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:28][C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[CH:31][N:30]=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:27])[CH2:18][C:19]3[CH:24]=[C:23]([F:25])[C:22]([C:33]4[CH:32]=[CH:31][N:30]=[C:29]([CH3:28])[CH:34]=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 58447659N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(6-chloro-5-fluoropyridin-3-yl)acetamide

Product 1

HCID 46927296US10251893, Cpd 190

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-fluoropyridin-3-yl)acetamide 190-5 (59 mg, 0.15 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine 183-2 (49 mg, 0.23 mmol), Pd(PPh3)4 (9 mg, 0.08 mmol), Na2CO3 (79 mg, 0.75 mmol), Toluene (0.8 mL), H2O (0.8 mL) and ethanol (0.2 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-(3-fluoro-2′-methyl-2,4′-bipyridin-5-yl)acetamide 190. MS m/z 449.2 (M+1); 1H NMR 400 MHz (MeOD) δ 8.48-8.46(m, 2H), 7.96(s, 1H), 7.87(d, 1H), 7.81(s, 1H), 7.75-7.69(m, 2 Hz), 7.36(dd, 1H), 3.84(s, 2H), 3.67(t, 2H), 3.62(t, 2H), 3.13(t, 2H), 3.08(t, 2H), 2.56(s, 3H), 2.08(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-c70d31b70e3b4720bc51e76d8aecb0cc
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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