1-Methylpiperazine → (R)-8-cyclopentyl-7-ethyl-5-methyl-2-(4-methylpiperazin-1-yl)-7,8-dihydropteridin-6(5H)-one

HRID 44878Notes

Reaction equation

HRID 44878 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:12])[C:7](=[O:13])[C@@H:6]([CH2:14][CH3:15])[N:5]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:4]=2[N:3]=1.[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>CS(C)=O.O>[CH:16]1([N:5]2[C:4]3[N:3]=[C:2]([N:25]4[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]4)[N:11]=[CH:10][C:9]=3[N:8]([CH3:12])[C:7](=[O:13])[C@H:6]2[CH2:14][CH3:15])[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 2

HCID 531671-MethylpiperazineHCID 24820413(R)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

Product 1

HCID 58405716(R)-8-cyclopentyl-7-ethyl-5-methyl-2-(4-methylpiperazin-1-yl)-7,8-dihydropteridin-6(5H)-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Intermediate B (114 mg, 0.39 mmol) and N-methylpiperazine (2 mmol, 6 eq, 204 mg, 0.22 mL) in 1 mL of DMSO was heated at 120° C. in a microwave for 2 h. The reaction was diluted with water and extracted with EtOAc. The organic extracts were washed 5× with water, then dried with MgSO4 and evaporated. The residue was purified by reverse-phase HPLC (eluting with 10-30% acetonitrile in water with 0.1% TFA over 20 min; Phenomenex Luna C-18 column, 25×2 cm) to give the title compound after lyophylization. LCMS: 359.2 m/z (M+H)+; ret. Time: 6.72 min (Analytical Method A); 1H NMR (400 MHz, CDCl3) δ: 7.6 (s, 1H), 4.3 (ddd, 1H), 4.1 (dd, 1H), 4.8 (broad s, 4H), 3.3 (s, 3H), 2.5 (broad s, 4H), 2.3 (s, 3H), 2.1-1.6 (m, 10H) and 0.9 ppm (dd, 3H).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic extracts were washed 5× with water
  3. dry with materialdried with MgSO4
  4. customevaporated
  5. customThe residue was purified by reverse-phase HPLC (eluting with 10-30% acetonitrile in water with 0.1% TFA over 20 min; Phenomenex Luna C-18 column, 25×2 cm)

Sources & evidence

ORD record
ord-7dae1b7d55e24f50a256b16c6201eee8
Source dataset
uspto-grants-2013_09
Patent number
US08541418B2

Reaction notes

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