1-Methylpiperazine → HCID 53476894, compound

HRID 408818Notes

Reaction equation

HRID 408818 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[C:8](Cl)=[N:9][C:10]([CH3:18])=[N:11][C:12]=1[NH:13][C@H:14]([CH3:17])[CH2:15][OH:16])=O.[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(N(C(C)C)CC)(C)C>CC(O)C>[Cl:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[C:4]1[N:13]([C@H:14]([CH3:17])[CH2:15][OH:16])[C:12]2[C:7]([N:6]=1)=[C:8]([N:28]1[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]1)[N:9]=[C:10]([CH3:18])[N:11]=2

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 58459061HCID 58459061, compound

Product 1

HCID 53476894HCID 53476894, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
160 °C

Procedure

Combine 2-chloro-N-[4-chloro-6-[[(1R)-2-hydroxy-1-methyl-ethyl]amino]-2-methyl-pyrimidin-5-yl]benzamide (13.0 g), IPA (11 mL), of N-methylpiperizine (7.1 mL) and diisopropylethylamine (7.0 mL) in a 300 mL Parr autoclave with mechanical stirrer. Seal the reaction vessel and heat to 160° C. for 24 h. Evaporate all volatile materials, dissolve in dichloromethane (100 mL) to give a dark solution. Wash with water (2×50 mL), dry using a hydrophobic frit, and evaporate all the solvent under reduced pressure. Take the resulting solid and dissolve in acetonitrile (85 mL) and stir. After 1.5 h collect the solids by filtration and air dry, before dying under vacuum to provide the title compound (10.73 g). Determine optical purity by chiral SFC to show a single enantiomer. ES/MS m/z 401.2 (M+1). Chiral HPLC conditions: Diacel AD-H, 10% IPA, 0.2% isopropylamine, 89.8% supercritical carbon dioxide, UV (220 nm), TR=4.22 min, 100% ee.

Workup

  1. customSeal the reaction vessel
  2. customEvaporate all volatile materials
  3. dissolutiondissolve in dichloromethane (100 mL)
  4. customto give a dark solution
  5. washWash with water (2×50 mL)
  6. customdry
  7. customevaporate all the solvent under reduced pressure
  8. dissolutiondissolve in acetonitrile (85 mL)
  9. customAfter 1.5 h collect the solids
  10. filtrationby filtration and air
  11. customdry

Sources & evidence

ORD record
ord-47cd499ef40140a29192324cb3f2efca
Source dataset
uspto-grants-2014_06
Patent number
US08759360B2

Reaction notes

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