Sodium Bicarbonate → 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-methyl-1-{4-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,3,5]triazin-2-yl}-urea

HRID 1038741Notes

Reaction equation

HRID 1038741 reaction equation
[CH3:1][NH:2][C:3]1[N:8]=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:23][C:24]1[C:29]([O:30][CH3:31])=[CH:28][C:27]([O:32][CH3:33])=[C:26]([Cl:34])[C:25]=1[N:35]=[C:36]=[O:37].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[Cl:23][C:24]1[C:29]([O:30][CH3:31])=[CH:28][C:27]([O:32][CH3:33])=[C:26]([Cl:34])[C:25]=1[NH:35][C:36](=[O:37])[N:2]([CH3:1])[C:3]1[N:8]=[C:7]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([N:16]3[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]3)=[CH:14][CH:15]=2)[N:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 66669974HCID 66669974, compoundHCID 860869932,6-Dichloro-3,5-dimethoxyphenyl isocyanate

Product 1

HCID 577102933-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-methyl-1-{4-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,3,5]triazin-2-yl}-urea

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2,6-dichloro-3,5-dimethoxy-aniline (124 mg, 0.56 mmol; Preparation 2) in 2 ml of dioxane under a nitrogene atmosphere, phosgene (0.52 ml 20% in toluene, 0.98 mmol) is added. The mixture is stirred for 70 min at 100° C., cooled to RT and concentrated in vacuo, yielding 2,6-dichloro-3,5-dimethoxyphenylisocyanate. The resulting solid is added portion-wise to a boiling solution of N-methyl-N′-[4-(4-methyl-piperazin-1-yl)-phenyl]-[1,3,5]triazine-2,4-diamine (140 mg, 0.47 mmol) in 8 ml of toluene during 20 min. After 3 h, another 2 eq of 2,6-dichloro-3,5-dimethoxyphenylisocyanate are added and stirring is continued for totally 5 h. Then the reaction mixture is diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted twice with DCM. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; DCM/MeOH/NH3aq, 97:3:0.2) gives the title compound: ESI-MS: 547/549 [MH]+; tR=3.5 min (purity: 100%, gradient J); TLC: Rf=0.40 (DCM/MeOH+1% NH3aq, 95:5).

Workup

  1. waitis continued for totally 5 h
  2. customThe aqueous layer is separated
  3. extractionextracted twice with DCM
  4. washThe organic phases are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d69878926ac6422b822b31e83fa3064e
Source dataset
uspto-grants-2013_10
Patent number
US08552002B2

Reaction notes

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