HCID 66669752, compound → 1-(2,6-Dichloro-3,5-dimethoxy-phenyl)-3-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-urea
Reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[N:13]=[C:14]=[O:15].[CH2:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:29]=[CH:28][C:27]([NH:30][C:31]3[CH:36]=[C:35]([NH2:37])[N:34]=[CH:33][N:32]=3)=[CH:26][CH:25]=2)[CH2:20][CH2:19]1)[CH3:17]>CN1C(=O)CCC1>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[NH:13][C:14]([NH:37][C:35]1[CH:36]=[C:31]([NH:30][C:27]2[CH:28]=[CH:29][C:24]([N:21]3[CH2:22][CH2:23][N:18]([CH2:16][CH3:17])[CH2:19][CH2:20]3)=[CH:25][CH:26]=2)[N:32]=[CH:33][N:34]=1)=[O:15]Participants
4
Conditions
- Temperature
- 70 °C
Procedure
2,6-dichloro-3,5-dimethoxyphenylisocyanate (1.2 eq.) is added to a solution of N-[4-(4-ethyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamine (350 mg, 1.18 mmol) in NMP (2 ml), at 70° C. and under an argon atmosphere. The resulting mixture is stirred at 70° C. for 2 h, allowed to cool to RT and concentrated. The residue is diluted with DCM and a saturated aqueous solution of sodium bicarbonate. The aqueous layer is separated and extracted with DCM. The organic phase is washed with brine, dried (sodium sulfate), filtered and concentrated. Purification of the crude product by trituration in MeOH followed by silica gel column chromatography (DCM/MeOH+1% NH3aq, 97:3) affords the title compound as a white solid:
Workup
- temperatureto cool to RT
- concentrationconcentrated
- additionThe residue is diluted with DCM
- customThe aqueous layer is separated
- extractionextracted with DCM
- washThe organic phase is washed with brine
- dry with materialdried (sodium sulfate)
- filtrationfiltered
- concentrationconcentrated
- customPurification of the crude product by trituration in MeOH
Sources & evidence
- ORD record
- ord-87dcb4c970bc4d7da086923456dfaf1b
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08552002B2
Reaction notes
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