N-methyl-N'-[4-(4-methyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamine → 3-(2,6-Dichloro-3-methoxy-phenyl)-1-methyl-1-(6-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl)-urea

HRID 1038666Notes

Reaction equation

HRID 1038666 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][NH:15][C:16]1[CH:21]=[C:20]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[N:19]=[CH:18][N:17]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([Cl:10])[C:3]=1[NH:11][C:12](=[O:13])[N:15]([CH3:14])[C:16]1[CH:21]=[C:20]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[N:19]=[CH:18][N:17]=1

Participants

4

Reactant 2

HCID 66669969N-methyl-N'-[4-(4-methyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamineHCID 860869342,6-Dichloro-3-methoxyphenylisocyanate

Product 1

HCID 565947453-(2,6-Dichloro-3-methoxy-phenyl)-1-methyl-1-(6-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl)-urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2,6-dichloro-3-methoxyphenylisocyanate (preparation 1, 52.3 mg, 0.24 mmol, 1.2 eq.) in toluene (2.5 ml) is added N-methyl-N′-[4-(4-methyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamine (59.7 mg, 0.2 mmol, 1.0 eq.). The obtained suspension is stirred under argon at 110° C. for 17 h. After cooling the crude product is filtered off und purified by flash chromatography (100% DCM to 5% MeOH in DCM within 35 min). Fractions containing the product are pooled and evaporated to dryness. The residue is triturated with ether (2 ml) and treated with ultra sound until a homogeneous suspension is obtained. The precipitate is filtered off and vacuum dried at 60° C. over night to afford the title compound as a colorless powder: m.p. 161.5-163° C., HPLC: tR=5.07 min (purity: >99%, gradient A), ESI-MS: 516.6/518.5/520.4 [MH]+.

Workup

  1. filtrationis filtered off
  2. customund purified by flash chromatography (100% DCM to 5% MeOH in DCM within 35 min)
  3. additionFractions containing the product
  4. customevaporated to dryness
  5. customThe residue is triturated with ether (2 ml)
  6. additiontreated with ultra sound until a homogeneous suspension
  7. customis obtained
  8. filtrationThe precipitate is filtered off
  9. customvacuum dried at 60° C. over night

Sources & evidence

ORD record
ord-95936e6814f846debfc0c4e93d84ca61
Source dataset
uspto-grants-2013_10
Patent number
US08552002B2

Reaction notes

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