1,2-Dichloroethane → [4-Chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[5-(2-methylamino-pyridin-4-yloxy)-benzoxazol-2-yl]-amine

HRID 491662Notes

Reaction equation

HRID 491662 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][CH3:16])N=2)[CH:5]=[CH:4][C:3]=1[OH:17].[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.[CH2:36](Cl)CCl>CC#N>[Cl:18][C:19]1[CH:32]=[CH:31][C:30]([NH:33][C:34]2[O:17][C:3]3[CH:4]=[CH:5][C:6]([O:8][C:9]4[CH:14]=[CH:13][N:12]=[C:11]([NH:15][CH3:16])[CH:36]=4)=[CH:7][C:2]=3[N:1]=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

5

Reactant 3

HCID 111,2-DichloroethaneHCID 17755112HCID 17755112, compoundHCID 177558431-(2-Chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine

Product 1

HCID 69017214[4-Chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[5-(2-methylamino-pyridin-4-yloxy)-benzoxazol-2-yl]-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

To a solution of 2-amino-4-(2-methylamino-pyrimidin-4-yloxy)-phenol (Step E, 0.143 g, 0.616 mmol) in 30 mL CH3CN was added dropwise over 5 min a solution 1-(2-chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine (0.174 g, 0.616 mmol) in 10 mL CH3CN. The reaction was stirred 18 h at RT. The reaction was diluted with 10 mL CH3CN, then EDC (0.118 g, 0.616 mmol) was added. The reaction was heated at 80° C. for 3 h. The reaction was cooled to RT then concentrated in vacuo. The crude mix was dissolved in EtOAc and H2O. The layers were separated, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by a combination of silica gel column chromatography and silica gel prep plates to obtain the title compound. MS (MH+)=480.2; MW Calc'd 479.97 for C24H26ClN7O2.

Workup

  1. temperatureThe reaction was heated at 80° C. for 3 h
  2. temperatureThe reaction was cooled to RT
  3. concentrationthen concentrated in vacuo
  4. additionThe crude mix
  5. dissolutionwas dissolved in EtOAc
  6. customThe layers were separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by a combination of silica gel column chromatography and silica gel prep plates

Sources & evidence

ORD record
ord-b74d67a7b5dc416bb856d30dc5ee4bb4
Source dataset
uspto-grants-2009_05
Patent number
US07531553B2

Reaction notes

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