Potassium Carbonate → N-[2-methyl-5-(1H-pyrazol-5-yl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide

HRID 1515207Notes

Reaction equation

HRID 1515207 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:34])=[C:6]([NH:8][C:9](=[O:33])[C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[N:26]=[C:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]=3)=[CH:12][CH:11]=2)[CH:7]=1.[N:35]1[N:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[CH3:34][C:5]1[CH:4]=[CH:3][C:2]([C:37]2[NH:36][N:35]=[CH:39][CH:38]=2)=[CH:7][C:6]=1[NH:8][C:9](=[O:33])[C:10]1[CH:11]=[CH:12][C:13]([NH:16][C:17]2[N:26]=[C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 57662893N-(5-bromo-2-methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamideHCID 66602990(1H-Pyrazol-1-yl)boronic acid

Product 1

HCID 57662925N-[2-methyl-5-(1H-pyrazol-5-yl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamideYield 69%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of N-(5-bromo-2-methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide (116 mg, 0.228 mmol), pyrazole-2-boronic acid (218 mg, 1.9 mmol), potassium carbonate (1.4 mmol) and tetrakis(triphenylphosphine)palladium (27 mg, 0.023 mmol) in dioxane (2 mL) was heated to 110° C. overnight. The reaction was cooled, concentrated on a rotary evaporator and purified by preparative reverse phase HPLC to give N-[2-methyl-5-(1H-pyrazol-5-yl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide (78 mg, 69%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.33 (s, 1H), 9.79 (s, 1H), 8.18 (d, 2H), 8.02 (d, 2H), 7.86 (m, 3H), 7.80 (m, 3H), 7.70 (s, 1H), 7.64 (m, 3H), 7.60 (dd, 1H), 7.42 (dt, 1H), 7.31 (d, 1H), 6.69 (d, 1H), 2.50 (s, 3H). MS (EI) for C31H24N6O: 497.1 (MH+).

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated on a rotary evaporator
  3. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-436ff1f3616f452695ee849b853ac1b0
Source dataset
uspto-grants-2012_07
Patent number
US08222263B2

Reaction notes

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