Cycloheptylamine → 6-chloro-N-(3-chloro-4-methoxyphenyl)-N'-cycloheptyl-[1,3,5]triazine-2,4-diamine

HRID 916133Notes

Reaction equation

HRID 916133 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[C:15](Cl)[N:14]=[C:13]([Cl:18])[N:12]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].N1C(Cl)=NC(Cl)=NC=1Cl.ClC1C=C(C=CC=1OC)N.[CH:38]1([NH2:45])[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1.[OH-].[Na+]>CC(C)=O>[Cl:18][C:13]1[N:12]=[C:11]([NH:10][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([Cl:1])[CH:3]=2)[N:16]=[C:15]([NH:45][CH:38]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[N:14]=1

Participants

7

Reactant 5

HCID 2899CycloheptylamineHCID 7954Cyanuric chlorideHCID 14798Sodium HydroxideHCID 214413-Chloro-4-methoxyanilineHCID 21896921(3-Chloro-4-methoxy-phenyl)-(4,6-dichloro-[1,3,5]triazin-2-yl)-amine

Product 1

HCID 218970216-chloro-N-(3-chloro-4-methoxyphenyl)-N'-cycloheptyl-[1,3,5]triazine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Among the bases and solvents screened, sodium acetate (NaOAc) and 1,4-dioxane showed consistently good results for a 1 kg preparation. This scheme involves the preparation of compound 101 by reaction of cyanuric chloride with 3-chloro-4-methoxyaniline in acetone at 0-5° C. in the absence of base, which is then made to react with cycloheptylamine in presence of NaOH under reflux to give compound 133. This compound 133 was reacted with 1-methyl-(4-methylamino)piperidine using NaOAc in 1,4-dioxane solvent to yield the crude compound 137 which is purified by making hydrochloride salt, N-(3-chloro-4-methoxyphenyl)-N′-cycloheptyl-N″-methyl-N″-(1-methylpiperidin-4-yl)[1,3,5]triazine-2,4,6-triamine, HCl salt, compound E31 and by recrystallisation in isopropanol. The hydrochloride salt was then released to give the free base, compound 137. Compound obtained in this manner exhibited the same high quality of appearance, purity, low residual solvents, assay and impurity profile, and the like.

Workup

  1. temperatureunder reflux

Sources & evidence

ORD record
ord-24ad1204f9f64a329e035e3abc679ce0
Source dataset
uspto-grants-2007_09
Patent number
US07268134B2

Reaction notes

Loading…