Cyclopropanemethanamine → 1-(6-[(Cyclopropylmethyl)amino]pyrazin-2-yl]-1H-benzimidazol-6-amine

HRID 2192687Notes

Reaction equation

HRID 2192687 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14]([NH2:17])[CH:15]=[CH:16][C:11]=3[N:10]=[CH:9]2)[CH:5]=[N:4][CH:3]=1.[CH:18]1([CH2:21][NH2:22])[CH2:20][CH2:19]1.CCN(C(C)C)C(C)C>C(OC(O)C)C>[CH:18]1([CH2:21][NH:22][C:2]2[N:7]=[C:6]([N:8]3[C:12]4[CH:13]=[C:14]([NH2:17])[CH:15]=[CH:16][C:11]=4[N:10]=[CH:9]3)[CH:5]=[N:4][CH:3]=2)[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 75646CyclopropanemethanamineHCID 81531DiisopropylethylamineHCID 582170941-(6-chloropyrazin-2-yl)-1H-benzimidazol-6-amine

Product 1

HCID 597839471-(6-[(Cyclopropylmethyl)amino]pyrazin-2-yl]-1H-benzimidazol-6-amine

Reagents, catalysts & solvents 1

HCID 101298981-EthoxyethanolSolvent

Procedure

A solution of 1-(6-chloropyrazin-2-yl)-1H-benzimidazol-6-amine (100 mg, 0.41 mmol) and cyclopropylmethylamine (424 μL, 4.1 mmol) in ethoxyethanol (2 mL) containing DIPEA (140 μL) was heated at reflux overnight under N2. The solution was concentrated under reduced pressure and the residue dissolved in EtOAc (20 mL) and washed successively with H2O (20 mL), 1M HCl (2×20 mL), H2O (20 mL) and brine (20 mL). After drying (Na2SO4) the solvent was removed under reduced pressure and the residue chromatographed eluting with dichloromethane-methanol (9:1-94:6) to separate pure product from the lower fractions (98 mg)

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight under N2
  3. concentrationThe solution was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in EtOAc (20 mL)
  5. washwashed successively with H2O (20 mL), 1M HCl (2×20 mL), H2O (20 mL) and brine (20 mL)
  6. dry with materialAfter drying (Na2SO4) the solvent
  7. customwas removed under reduced pressure
  8. customthe residue chromatographed
  9. washeluting with dichloromethane-methanol (9:1-94:6)
  10. customto separate pure product from the lower fractions (98 mg)

Sources & evidence

ORD record
ord-255747a51e3945df962dd3c11b5da6e9
Source dataset
uspto-grants-2012_12
Patent number
US08329737B2

Reaction notes

Loading…