Potassium Carbonate → 8-Bromo-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione

HRID 2172566Notes

Reaction equation

HRID 2172566 reaction equation
[CH3:1][N:2]1[C:10]2[N:9]=[C:8]([Br:11])[N:7]([CH2:12][C:13]#[C:14][CH3:15])[C:6]=2[C:5](=[O:16])[NH:4][C:3]1=[O:17].CN(C)C(=O)C.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:31][C:32]1[N:41]=[C:40]([CH3:42])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1>O>[CH3:42][C:40]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=[C:32]([CH2:31][N:4]2[C:5](=[O:16])[C:6]3[N:7]([CH2:12][C:13]#[C:14][CH3:15])[C:8]([Br:11])=[N:9][C:10]=3[N:2]([CH3:1])[C:3]2=[O:17])[N:41]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 2415182-(Chloromethyl)-4-methylquinazolineHCID 210889278-Bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1H-purine-2,6-dione

Product 1

HCID 247500498-Bromo-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dioneYield 70.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

3-Methyl-7-(2-butyn-l-yl)-8-bromo-xanthine (10 gm) and N,N-dimethylacetamide (150 mL) were charged into a 1000 mL round bottomed flask equipped with a mechanical stirrer. Potassium carbonate (9.3 gm) and 2-(chloromethyl)-4-methylquinazoline (6.8 gm) were added to the reaction mixture at room temperature. The reaction mixture was heated to 90° C. and maintained the temperature for 8 hours. The reaction mixture was cooled to 30° C. and water (450 mL) was added and the mixture was stirred for 1 hour at 30° C. The solid formed was collected by filtration and washed with water (150 mL). The wet cake was charged into 500 mL round bottomed flask and toluene (220 mL) was added and the mixture was heated to reflux temperature and maintained for 1 hour. The mixture was cooled to 10° C. and maintained for 2 hours. The solid was collected by filtration and washed with toluene (50 mL). The solid was dried in oven under vacuum at 80° C. to get 10.8 gm of the title compound. Purity by HPLC: 99.59%

Workup

  1. customequipped with a mechanical stirrer
  2. temperaturemaintained the temperature for 8 hours
  3. temperatureThe reaction mixture was cooled to 30° C.
  4. customThe solid formed
  5. filtrationwas collected by filtration
  6. washwashed with water (150 mL)
  7. additionThe wet cake was charged into 500 mL round bottomed flask
  8. additiontoluene (220 mL) was added
  9. temperaturethe mixture was heated
  10. temperatureto reflux temperature
  11. temperaturemaintained for 1 hour
  12. temperatureThe mixture was cooled to 10° C.
  13. temperaturemaintained for 2 hours
  14. filtrationThe solid was collected by filtration
  15. washwashed with toluene (50 mL)
  16. customThe solid was dried in oven under vacuum at 80° C.

Sources & evidence

ORD record
ord-c969ddd8a10d4a24ace647c3c1f3b832
Source dataset
uspto-grants-2015_06
Patent number
US09056112B2

Reaction notes

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