Cesium carbonate → 4-amino-8-((8-chloro-2-(2-chlorophenyl)-quinolin-3-yl)methyl)pyrido[2,3-d]pyrimidin-5(8H)-one

HRID 2074514Notes

Reaction equation

HRID 2074514 reaction equation
[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:19][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:29]=1[N:28]=[C:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:36])[C:26]([CH2:37]Cl)=[CH:25]2>CN(C=O)C>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH2:37][C:26]3[C:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[Cl:36])=[N:28][C:29]4[C:24]([CH:25]=3)=[CH:23][CH:22]=[CH:21][C:20]=4[Cl:19])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 57067884-aminopyrido[2,3-d]pyrimidin-5(8H)-oneHCID 592646338-Chloro-3-(chloromethyl)-2-(2-chlorophenyl)quinoline

Product 1

HCID 575561924-amino-8-((8-chloro-2-(2-chlorophenyl)-quinolin-3-yl)methyl)pyrido[2,3-d]pyrimidin-5(8H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of 4-aminopyrido[2,3-d]pyrimidin-5(8H)-one (0.05 g, 0.308 mmol), Cs2CO3 (0.1515 g, 0.46 mmol, 1.5 eq), and KI (0.0051 g, 0.0309 mmol, 0.1 eq) in DMF (1 mL) was added 8-chloro-3-(chloromethyl)-2-(2-chlorophenyl)quinoline (0.1 g, 0.309 mmol, 1.0 eq) and the mixture was stirred at 140° C. for 1 h. The mixture was concentrated under reduced pressure. The crude product was purified by column chromatography on a 40 g of Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane over 14 min and then 100% isocratic of EtOAc for 14 min as eluent to provide 4-amino-8-((8-chloro-2-(2-chlorophenyl)quinolin-3-yl)methyl)pyrido[2,3-d]pyrimidin-5(8H)-one [PI3Kδ IC50=33 nM] as white solid. 1H NMR (DMSO-d6) δ ppm 9.52 (1 H, d, J=4.7 Hz), 8.25 (1 H, s), 8.11 (1 H, d, J=4.7 Hz), 8.09 (1 H, s), 8.04 (1 H, dd, J=8.4, 1.4 Hz), 7.97 (1 H, dd, J=7.6, 1.4 Hz), 7.81 (1 H, d, J=7.8 Hz), 7.63 (1 H, d, J=7.8 Hz), 7.57-7.61 (1 H, m), 7.42-7.53 (3 H, m), 6.14 (1 H, d, J=7.8 Hz), 5.40 (2 H, s). Mass Spectrum (ESI) m/e=448.0 and 450.1 (M+1).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customThe crude product was purified by column chromatography on a 40 g of Redi-Sep™ column
  3. customover 14 min

Sources & evidence

ORD record
ord-ccf46f46da9344db9eaee1593aec1da7
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

Loading…