Sodium Bicarbonate → 3-(2,6-Dichloro-3-trifluoromethyl-Phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea

HRID 1038748Notes

Reaction equation

HRID 1038748 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[C:20]([NH:22][CH3:23])[N:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2].[Cl:24][C:25]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[C:27]([Cl:35])[C:26]=1[N:36]=[C:37]=[O:38].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[Cl:24][C:25]1[C:30]([C:31]([F:32])([F:34])[F:33])=[CH:29][CH:28]=[C:27]([Cl:35])[C:26]=1[NH:36][C:37](=[O:38])[N:22]([C:20]1[CH:21]=[C:16]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([N:6]3[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:8][CH2:7]3)=[CH:14][CH:13]=2)[N:17]=[CH:18][N:19]=1)[CH3:23]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 56594616N4-(4-(4-Ethyl-1-piperazinyl)phenyl)-N6-methyl-4,6-pyrimidinediamineHCID 866307212,6-Dichloro-3-trifluoromethyl-phenylisocyanate

Product 1

HCID 577104183-(2,6-Dichloro-3-trifluoromethyl-Phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

This oil is re-dissolved in 2 ml of toluene and added portion-wise to a boiling solution of N-[4-(4-ethyl-piperazin-1-yl)-phenyl]-N′-methyl-pyrimidine-4,6-diamine (156 mg, 0.50 mmol; Example 145A) in 6 ml of toluene during 10 min. After 1.5 h, another 2 eq of 2,6-dichloro-3-trifluoromethyl-phenylisocyanate are added and stirring is continued for totally 2 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; CH2Cl2/MeOH/NH3aq, 95:5:0.5) gives the title compound: ESI-MS: 568/570 [MH]+; tR=4.1 min (gradient J); TLC: Rf=0.3 (DCM/MeOH+1% NH3aq, 95:5).

Workup

  1. waitis continued for totally 2 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-9976bfbfa96b4a6c80d1e1e9022402f4
Source dataset
uspto-grants-2013_10
Patent number
US08552002B2

Reaction notes

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