1,2-Dichloroethane → HCID 178474213, compound

HRID 491636Notes

Reaction equation

HRID 491636 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[NH2:19])[O:5][C:6]1[CH:7]=[C:8]([NH:12][C:13](=[O:15])[CH3:14])[CH:9]=[CH:10][CH:11]=1.[Cl:20][C:21]1[CH:34]=[CH:33][C:32]([N:35]=[C:36]=S)=[CH:31][C:22]=1[CH2:23][N:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1.C(Cl)CCl>CC#N>[Cl:20][C:21]1[CH:34]=[CH:33][C:32]([NH:35][C:36]2[NH:19][C:18]3[CH:17]=[CH:16][C:4]([O:5][C:6]4[CH:7]=[C:8]([NH:12][C:13](=[O:15])[CH3:14])[CH:9]=[CH:10][CH:11]=4)=[CH:3][C:2]=3[N:1]=2)=[CH:31][C:22]=1[CH2:23][N:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 17755037N-[3-(3,4-Diamino-phenoxy)-phenyl]-acetamideHCID 177558431-(2-Chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine

Product 1

HCID 178474213HCID 178474213, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of N-[3-(3,4-diamino-phenoxy)-phenyl]-acetamide (Step B, 320 mg, 1.2 mmol, 1.0 eq.) in 20 mL of anhydrous CH3CN was added drop-wise to a solution of 1-(2-chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine (300 mg, 1.2 mmol, 1.0 eq.) in 10 mL of CH3CN. The reaction was stirred for 2 h at RT. EDC (360 mg, 1.9 mmol, 1.5 eq.) was added and the reaction was heated to 80° C. and stirred for 1 h. The mixture was cooled and concentrated. The residue was dissolved into EtOAc and washed with H2O and sat. NaHCO3 (aq.). The organic layer was dried (MgSO4), filtered and concentrated. The crude was further purified by column chromatography (0-10% MeOH/CH2Cl2 with 1% NH4OH) followed by recrystallization from CH2Cl2 to give pure N-(3-{2-[4-chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenylamino]-1H-benzimidazol-5-yloxy}-phenyl)-acetamide. MS m/z=506.2 (M+H)+; Calc'd for C27H29N6O2: 504.20.

Workup

  1. temperaturethe reaction was heated to 80° C.
  2. stirringstirred for 1 h
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved into EtOAc
  6. washwashed with H2O and sat. NaHCO3 (aq.)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude was further purified by column chromatography (0-10% MeOH/CH2Cl2 with 1% NH4OH)
  11. customfollowed by recrystallization from CH2Cl2

Sources & evidence

ORD record
ord-9e06ca3c534041ac84d337b13dcab6f7
Source dataset
uspto-grants-2009_05
Patent number
US07531553B2

Reaction notes

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