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

HRID 2074491Notes

Reaction equation

HRID 2074491 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[CH2:20][C:21]1[C:22]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:38])=[N:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:31]>CN(C=O)C>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH2:20][C:21]3[C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[Cl:38])=[N:23][C:24]4[C:29]([CH:30]=3)=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:31])[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 575561573-(Chloromethyl)-2-(2-chlorophenyl)-8-methylquinoline

Product 1

HCID 250960324-amino-8-((2-(2-chlorophenyl)-8-methyl-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 (0.1 g, 0.616 mmol), Cs2CO3 (0.3013 g, 0.925 mmol, 1.5 eq), and KI (0.0102 g, 0.0616 mmol, 0.1 eq) in DMF (2 mL) was added 3-(chloromethyl)-2-(2-chlorophenyl)-8-methyl-quinoline (0.2049 g, 0.678 mmol, 1.1 eq) and the mixture was stirred at 140° C. for 2.5 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 10 min as eluent to provide 4-amino-8-((2-(2-chlorophenyl)-8-methylquinolin-3-yl)methyl)pyrido[2,3-d]pyrimidin-5(8H)-one as white solid. The white solid was triturated with EtOAc-Hexane (1:1) and filtered to provide 4-amino-8-((2-(2-chlorophenyl)-8-methylquinolin-3-yl)methyl)pyrido[2,3-d]pyrimidin-5(8H)-one [PI3Kδ IC50=58 nM] as white solid. 1H NMR (DMSO-d6) δ ppm 9.53 (1 H, d, J=4.7 Hz), 8.13 (1 H, s), 8.04-8.11 (2 H, m), 7.84 (1 H, d, J=7.8 Hz), 7.78 (1 H, d, J=7.8 Hz), 7.64 (1 H, d, J=7.0 Hz), 7.38-7.59 (5 H, m), 6.12 (1H, d, J=7.8 Hz), 5.40 (2 H, d, J=6.3 Hz), 2.64 (3 H, s). Mass Spectrum (ESI) m/e=428.0 (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-18551345bae64475adcabc753afac2b8
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

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