1,2-Dichloroethane → HCID 178503458, compound

HRID 491641Notes

Reaction equation

HRID 491641 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[CH:11]=[C:12]([NH2:17])[C:13]([NH2:16])=[CH:14][CH:15]=2)[CH:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:32]=[CH:31][C:30]([N:33]=[C:34]=S)=[CH:29][C:20]=1[CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1.N1C=CN=C1.C(Cl)CCl>CC#N>[Cl:18][C:19]1[CH:32]=[CH:31][C:30]([NH:33][C:34]2[NH:16][C:13]3[CH:14]=[CH:15][C:10]([O:9][C:7]4[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=4)=[CH:11][C:12]=3[N:17]=2)=[CH:29][C:20]=1[CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 795ImidazoleHCID 177558431-(2-Chloro-5-isothiocyanato-benzyl)-4-methyl-piperazineHCID 177564954-(2-Methylsulfanyl-pyrimidin-4-yloxy)-benzene-1,2-diamine

Product 1

HCID 178503458HCID 178503458, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 4-(2-methylsulfanyl-pyrimidin-4-yloxy)-benzene-1,2-diamine (Step B, 400 mg, 1.6 mmol, 1.0 eq.) in anhydrous CH3CN (30 mL) was added dropwise a solution of 1-(2-chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine (900 mg [slightly contaminated with imidazole], 1.6 mmol, 1.0 eq.) in 20 mL of anhydrous CH3CN. The reaction was stirred for 16 h at RT then EDC (0.5 g, 2.6 mmol, 1.5 eq.) was added. The resulting mixture was heated to 80° C. for 1 h. The solvent was evaporated and the residue was diluted with CH2Cl2 (25 mL). The solution was washed with H2O (25 mL), NaHCO3 (25 mL, aq.) and brine (25 mL). The aqueous layers were back extracted with CH2Cl2 and the combined organic layers were dried over MgSO4, filtered and concentrated. The crude was further purified by column chromatography (0-7.5% MeOH/CH2Cl2) to give pure [4-chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[5-(2-methylsulfanyl-pyrimidin-4-yloxy)-1H-benzimidazol-2-yl]-amine. MS m/z=496.2 (M+H)+; MW Calc'd for C24H26N7OS: 495.16.

Workup

  1. temperatureThe resulting mixture was heated to 80° C. for 1 h
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with CH2Cl2 (25 mL)
  4. washThe solution was washed with H2O (25 mL), NaHCO3 (25 mL, aq.) and brine (25 mL)
  5. extractionThe aqueous layers were back extracted with CH2Cl2
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude was further purified by column chromatography (0-7.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-9602c747c50f474cb5ede6f5a1013245
Source dataset
uspto-grants-2009_05
Patent number
US07531553B2

Reaction notes

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