Toluene → 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-[6-(3-dimethylaminomethyl-phenylamino)-pyrimidin-4-yl]-1-ethyl-urea

HRID 1038721Notes

Reaction equation

HRID 1038721 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([Cl:10])[C:3]=1[N:11]=[C:12]=[O:13].[CH3:14][N:15]([CH2:17][C:18]1[CH:19]=[C:20]([NH:24][C:25]2[CH:30]=[C:29]([NH:31][CH3:32])[N:28]=[CH:27][N:26]=2)[CH:21]=[CH:22][CH:23]=1)[CH3:16].[C:33](=[O:36])(O)[O-].[Na+].[C:38]1(C)C=CC=CC=1>>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:36][CH3:33])=[C:4]([Cl:10])[C:3]=1[NH:11][C:12](=[O:13])[N:31]([C:29]1[CH:30]=[C:25]([NH:24][C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([CH2:17][N:15]([CH3:14])[CH3:16])[CH:19]=2)[N:26]=[CH:27][N:28]=1)[CH2:32][CH3:38]

Participants

5

Reactant 4

HCID 1140Toluene2×HCID 516892Sodium BicarbonateHCID 66669947N-(3-dimethylaminomethyl-phenyl)-N'-methyl-pyrimidine-4,6-diamineHCID 860869342,6-Dichloro-3-methoxyphenylisocyanate

Product 1

HCID 577103733-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-[6-(3-dimethylaminomethyl-phenylamino)-pyrimidin-4-yl]-1-ethyl-urea

Procedure

A suspension of 2,6-dichloro-3-methoxyphenylisocyanate (2 eq.) in toluene (3 ml) is added to a refluxing solution of N-(3-dimethylaminomethyl-phenyl)-N′-methyl-pyrimidine-4,6-diamine (216 mg, 0.80 mmol, 1 eq.) in toluene (3 ml), under an argon atmosphere. The resulting mixture is stirred at reflux for 2 h and allowed to cool to RT. The reaction mixture is diluted with EE and a saturated aqueous solution of sodium bicarbonate. The aqueous layer is separated and extracted with EE. The organic phase is washed with brine, dried (sodium sulfate), filtered and concentrated. Purification of the residue by silica gel column chromatography (DCM/MeOH+1% NH3aq, 95:5), followed by reversed phase MPLC purification (AcCN/H2O/TFA) of the resulting product, affords 161 mg of the title compound as a white solid: ESI-MS: 518.9/520.9 [MH]+; tR=3.76 min (purity: 100%, gradient J); TLC: Rf=0.21 (DCM/MeOH+1% NH3aq, 95:5).

Workup

  1. temperatureat reflux for 2 h
  2. additionThe reaction mixture is diluted with EE
  3. customThe aqueous layer is separated
  4. extractionextracted with EE
  5. washThe organic phase is washed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue by silica gel column chromatography (DCM/MeOH+1% NH3aq, 95:5)
  10. customfollowed by reversed phase MPLC purification (AcCN/H2O/TFA) of the resulting product

Sources & evidence

ORD record
ord-7d32fc64c3a4418a914d7cf84fd03610
Source dataset
uspto-grants-2013_10
Patent number
US08552002B2

Reaction notes

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