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

HRID 44899Notes

Reaction equation

HRID 44899 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].Cl[CH2:19][C:20]1[N:29]=[C:28]([CH3:30])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)(=O)C>C(O)C.O.CN1CCCC1=O>[CH3:30][C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([CH2:19][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:29]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 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-dione

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

10.00 kg (33.66 mol) of 3-methyl-7-(2-butin-1-yl)-8-bromoxanthine, 7.13 kg (37.02 mol) of 2-chloromethyl-4-methylquinazoline, 3.92 kg (37.02 mol) of anhydrous sodium carbonate and 30 liters of N-methyl-2-pyrrolidone are initially charged in the reactor. The reactor contents are heated to 140° C. and stirred at 140° C. for 2 hours. After the reaction has ended, the reaction mixture is cooled to 80° C. and diluted with 60 liters of 96% ethanol and subsequently at 70° C. with 55 liters of water. At 60° C., 4.04 kg (67.32 mol) of acetic acid are metered in and flushed in with 5 liters of water. The resulting suspension is stirred at 60° C. for 30 minutes, then cooled to 23° C. and stirred for a further 30 minutes. Subsequently, the product is centrifuged off and washed first with a mixture of 20 liters of 96% ethanol and 20 liters of water, then with 40 liters of 96% ethanol and 40 liters of water. Drying is effected at 45° C. in a drying cabinet under inertization.

Workup

  1. temperaturethe reaction mixture is cooled to 80° C.
  2. customAt 60° C.
  3. customflushed in with 5 liters of water
  4. stirringThe resulting suspension is stirred at 60° C. for 30 minutes
  5. temperaturecooled to 23° C.
  6. stirringstirred for a further 30 minutes
  7. washwashed first with a mixture of 20 liters of 96% ethanol and 20 liters of water
  8. customDrying
  9. customis effected at 45° C. in a drying cabinet under inertization

Sources & evidence

ORD record
ord-276199d856594960839766b0d7d15409
Source dataset
uspto-grants-2013_09
Patent number
US08541450B2

Reaction notes

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