Sodium Iodide → N-isopropyl-2-[2-(3-methoxyphenyl)-6-(1-methylpiperidin-3-ylmethoxy)-4-oxo-4H-quinazolin-3-yl]acetamide

HRID 1157476Notes

Reaction equation

HRID 1157476 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)[N:6]([CH2:20][C:21]([NH:23][CH:24]([CH3:26])[CH3:25])=[O:22])[C:5]2=[O:27].Cl[CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][N:32]([CH3:36])[CH2:31]1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CS(C)=O.ClCCl.O>[NH4+:6].[OH-:1].[CH:24]([NH:23][C:21](=[O:22])[CH2:20][N:6]1[C:5](=[O:27])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([O:1][CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][N:32]([CH3:36])[CH2:31]3)[CH:3]=2)[N:8]=[C:7]1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)([CH3:25])[CH3:26]

Participants

9

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 1036743-(Chloromethyl)-1-methylpiperidineHCID 685249242-[6-hydroxy-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide

Product 2

HCID 14923Ammonium HydroxideHCID 59511768N-isopropyl-2-[2-(3-methoxyphenyl)-6-(1-methylpiperidin-3-ylmethoxy)-4-oxo-4H-quinazolin-3-yl]acetamideYield 125.9%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-[6-hydroxy-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide (INTERMEDIATE IV.4) (100 mg, 0.27 mmol), 3-chloromethyl-1-methyl piperidine*HCl (50 mg, 0.27 mmol), caesium carbonate (443 mg, 1.36 mmol) and a catalytic amount of sodium iodide in DMSO (1 mL) was heated to 85° C. for 16 h. This was then cooled and poured into water (10 mL) and the resultant precipitate collected by filtration. Purification by chromatography on silica gel with methanol:dichloromethane:NH4OH (aq.) (20:179:1, v/v) as eluent afforded N-isopropyl-2-[2-(3-methoxyphenyl)-6-(1-methylpiperidin-3-ylmethoxy)-4-oxo-4H-quinazolin-3-yl]acetamide (EXAMPLE 14a) (82 mg, 0.17 mmol, 63%).

Workup

  1. temperatureThis was then cooled
  2. filtrationthe resultant precipitate collected by filtration
  3. customPurification by chromatography on silica gel with methanol

Sources & evidence

ORD record
ord-a98f434dd683462f90c269ebbaaa7f48
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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