Potassium Carbonate → [2-(4-Methylpiperidin-1-yl)-purin-4-yl]-(5-methyl-2H-pyrazol-3-yl)-amine

HRID 11833Notes

Reaction equation

HRID 11833 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:9]([NH:11][C:12]3[CH:16]=[C:15]([CH3:17])[NH:14][N:13]=3)([N:10]=1)[N:8]=[CH:7][N:6]=2.[CH3:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+]>>[CH3:18][CH:19]1[CH2:24][CH2:23][N:22]([C:2]2[N:3]=[CH:4][C:5]3[C:9]([NH:11][C:12]4[NH:13][N:14]=[C:15]([CH3:17])[CH:16]=4)([N:10]=2)[N:8]=[CH:7][N:6]=3)[CH2:21][CH2:20]1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 693814-MethylpiperidineHCID 21939154(2-chloro-purin-4-yl)-(5-methyl-1H-pyrazol-3-yl)-amine

Product 1

HCID 178419059[2-(4-Methylpiperidin-1-yl)-purin-4-yl]-(5-methyl-2H-pyrazol-3-yl)-amineYield 90%

Procedure

To a suspension of 2,4-dichloro-purine (2.0 g, 10.6 mmol) in anhydrous ethanol (10 mL) was added 5-methyl-1H-pyrazol-3-yl amine (2.05 g, 21.2 mmol). The resulting mixture was stirred at room temperature for 48 h. The resulting precipitate was collected by filtration, washed with ethanol, and dried under vacuum to afford 1.524 g (58% yield) of (2-chloro-purin-4-yl)-(5-methyl-1H-pyrazol-3-yl)-amine which was used in the next step without further purification. To a solution of (2-chloro-purin-4-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (200 mg, 0.80 mmol) was added 4-methylpiperidine (4 mL, 8.01 mmol) and the reaction mixture heated at reflux overnight. The solvent was evaporated and the residue dissolved in a mixture EtOH:water (1:3, 4 mL). Potassium carbonate (57 mg, 0.41 mmol) was added and the mixture was stirred at room temperature for 2 hours. The resulting suspension was filtered, washed with water (×2) and rinsed with Et2O (×2) to afford IV-33 as a white solid (225 mg, 90%): mp>300° C.; 1H NMR (DMSO) δ 0.91 (3H, d), 1.10 (2H, m), 1.65 (3H, m), 2.24 (3H, s), 2.84 (2H, m), 4.60 (2H, m), 6.40 (1H, s), 7.87 (1H, m), 9.37–9.59 (1H, m), 12.03–12.39 (2H, m); IR (solid) 1651, 1612, 1574, 1484, 1446, 1327, 1317, 1255, 1203; MS 313.3 (M+H)+.

Workup

  1. customwas used in the next step without further purification
  2. temperaturethe reaction mixture heated
  3. temperatureat reflux overnight
  4. customThe solvent was evaporated
  5. dissolutionthe residue dissolved in a mixture EtOH:water (1:3, 4 mL)
  6. filtrationThe resulting suspension was filtered
  7. washwashed with water (×2)
  8. washrinsed with Et2O (×2)

Sources & evidence

ORD record
ord-033fb5014fbd4547a14bf5c0235026b0
Source dataset
uspto-grants-2006_08
Patent number
US07098330B2

Reaction notes

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