Methyl iodide → N-{3-[{4-[(4-tert-butyl-1,3-thiazol-2(3H)-ylidene)(cyano)methyl]pyrimidin-2-yl}(methyl)amino]propyl}acetamide

HRID 2375320Notes

Reaction equation

HRID 2375320 reaction equation
[C:1]([C:5]1[NH:6][C:7](=[C:10]([C:25]#[N:26])[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH2:18][CH2:19][CH2:20][NH:21][C:22](=[O:24])[CH3:23])[N:12]=2)[S:8][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:27]C(C)([O-])C.[K+].CI.C(O)(C(F)(F)F)=O>C1COCC1.C(Cl)Cl.CCOCC>[C:1]([C:5]1[NH:6][C:7](=[C:10]([C:25]#[N:26])[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([N:17]([CH3:27])[CH2:18][CH2:19][CH2:20][NH:21][C:22](=[O:24])[CH3:23])[N:12]=2)[S:8][CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 23665647Potassium tert-butoxideHCID 69310017HCID 69310017, compound

Product 1

HCID 67068382N-{3-[{4-[(4-tert-butyl-1,3-thiazol-2(3H)-ylidene)(cyano)methyl]pyrimidin-2-yl}(methyl)amino]propyl}acetamideYield 35.4%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To suspension of N-[3-({4-[(4-tert-butyl-1,3-thiazol-2(3H)-ylidene)(cyano)methyl]pyrimidin-2-yl}amino)propyl]acetamide (290 mg, 0.68 mmol) in THF (7 ml) were added potassium tert-butoxide (91 mg, 0.81 mmol) and methyl iodide (0.085 mL, 1.35 mmol). The resulting mixture was stirred 2 h at rt. LC/MS analysis showed the presence two peaks with the same mass in a proportion of 7:3. The THF was evaporated and the residue was taken up in water and extracted with EtOAc (3×). The combined organic layer was washed with brine, dried with MgSO4 and the solvent was evaporated under reduced pressure to give a gummy residue which was the mixture of to compounds of the same mass. It was taken up in DCM and an excess TFA then ether were added to the solution. As no precipitation occurred, the solution was concentrated under reduced pressure and the residue was purified by preparative HPLC to give 93 mg of the title compound as a TFA salt pyrimidine (yellow solid, Y=27.3%).

Workup

  1. customThe THF was evaporated
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried with MgSO4
  5. customthe solvent was evaporated under reduced pressure
  6. customto give a gummy residue which
  7. additionthe mixture of to compounds of the same mass
  8. customAs no precipitation
  9. concentrationthe solution was concentrated under reduced pressure
  10. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-81dca2a2405e4f8f96aef52632b982dd
Source dataset
uspto-grants-2008_12
Patent number
US07465736B2

Reaction notes

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