Potassium Carbonate → 4-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (4-pyrimidin-5-yl-phenyl)-amide

HRID 657235Notes

Reaction equation

HRID 657235 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:29][CH3:30])=[C:24]([O:27][CH3:28])[CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.[N:31]1[CH:36]=[C:35](B(O)O)[CH:34]=[N:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CCO.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>[N:31]1[CH:36]=[C:35]([C:2]2[CH:3]=[CH:4][C:5]([NH:8][C:9]([N:11]3[CH2:12][CH2:13][CH:14]([C:17]4[C:26]5[C:21](=[CH:22][C:23]([O:29][CH3:30])=[C:24]([O:27][CH3:28])[CH:25]=5)[N:20]=[CH:19][N:18]=4)[CH2:15][CH2:16]3)=[O:10])=[CH:6][CH:7]=2)[CH:34]=[N:33][CH:32]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 587707304-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (4-iodo-phenyl)-amide

Product 1

HCID 587708234-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (4-pyrimidin-5-yl-phenyl)-amideYield 35.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 4-(6,7-dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (4-iodo-phenyl)-amide (58.2 mg, 0.11 mmol), as prepared in Example 2b, in 1 mL of toluene/EtOH (4:1, v/v) were added pyrimidine-5-boronic acid (15.3 mg, 0.12 mmol), Pd(PPh3)4 (6.5 mg) and 2M K2CO3 solution (0.23 mL). The reaction mixture was heated at 100° C. overnight. It was concentrated under reduced pressure and the black residue was purified by flash column chromatography on silica gel (5% MeOH/EtOAc as eluent) to afford the desired product (18.4 mg, 35.6% yield). 1H NMR (300 MHz, CDCl3) δ 9.17 (s, 1H), 9.09 (s, 1H), 8.94 (s, 2H), 7.55 (s, 4H), 7.38 (s, 1H), 7.27 (s, 1H), 6.59 (s, 1H), 4.32 (m, 2H), 4.09 (s, 3H), 4.08 (s, 3H), 3.65 (m, 1H), 3.23 (m, 2H), 2.19 (m, 2H), 2.03 (m, 2H). LC-MS (ESI) calcd mass 470.2, found 471.3 (MH+).

Workup

  1. concentrationIt was concentrated under reduced pressure
  2. customthe black residue was purified by flash column chromatography on silica gel (5% MeOH/EtOAc as eluent)

Sources & evidence

ORD record
ord-84b3837e219e4bc58ff8bc37afe1bc0e
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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