Tetrahydrofuran → 4-Methyl-6-[2-(1-methyl-2-pyrrolidinyl)ethyl]-2-pyrimidinamine

HRID 887624Notes

Reaction equation

HRID 887624 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:9]=[C:8](Cl)[CH:7]=[C:6]([CH3:11])[N:5]=1.[CH2:12]1[CH2:16]O[CH2:14][CH2:13]1>>[CH3:11][C:6]1[CH:7]=[C:8]([CH2:14][CH2:13][CH:12]2[CH2:16][CH2:7][CH2:6][N:5]2[CH3:4])[N:9]=[C:4]([NH2:3])[N:5]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 218102-Amino-4-chloro-6-methylpyrimidineHCID 24758Sodium hydride

Product 1

HCID 689822434-Methyl-6-[2-(1-methyl-2-pyrrolidinyl)ethyl]-2-pyrimidinamine

Procedure

To a solution of (S)-(−)-1-methyl-2-pyrrolidine (320 mg, 2.78 mmol) in dry THF (10 mL) at 0° C. was added NaH (167 mg, 4.16 mmol). After stirred at RT for 1 h, 2-amino-4-chloro-6-methylpyrimidine (600 mg, 4.16 mmol) in dry THF (10 mL) was added dropwise via the addition funnel. The resulting mixture was heated to reflux under Ar gas for 20 h. The reaction was cooled to RT and quenched with sat. NH4Cl. Solvent was removed. The residue was partitioned between H2O and CHCl3. The organic layer was washed with H2O, brine, dried over MgSO4, and evaporated to dryness. This crude compound was purified in column eluted with CH2Cl2:MeOH=95%:5% to yield the title compound. MS m/z: 223.2 (M+H). Calc'd. for C12H20N4—222.2.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux under Ar gas for 20 h
  3. temperatureThe reaction was cooled to RT
  4. customquenched with sat. NH4Cl
  5. customSolvent was removed
  6. customThe residue was partitioned between H2O and CHCl3
  7. washThe organic layer was washed with H2O, brine
  8. dry with materialdried over MgSO4
  9. customevaporated to dryness
  10. customThis crude compound was purified in column
  11. washeluted with CH2Cl2

Sources & evidence

ORD record
ord-76dc21c55bb5438b8edd6b14c13d2102
Source dataset
uspto-grants-2012_08
Patent number
US08247430B2

Reaction notes

Loading…