Acetyl chloride → Nalpha-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-methylamino-methyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester.hydrochloride

HRID 557447Notes

Reaction equation

HRID 557447 reaction equation
[CH:1]([O:4][C:5](=[O:43])[C@H:6]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:34](=[O:35])[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([CH2:36][N:37](C=O)[CH3:38])[CH:32]=3)[N:27]([CH3:41])[C:26]2=[O:42])=[CH:21][CH:20]=1)[NH:7][C:8](=[O:17])[C:9]1[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=1[Cl:16])([CH3:3])[CH3:2].C(Cl)(=O)C.C(OC(C)C)(=O)C>CC(O)C>[ClH:15].[CH:1]([O:4][C:5](=[O:43])[C@H:6]([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([N:25]2[C:34](=[O:35])[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([CH2:36][NH:37][CH3:38])[CH:32]=3)[N:27]([CH3:41])[C:26]2=[O:42])=[CH:23][CH:24]=1)[NH:7][C:8](=[O:17])[C:9]1[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=1[Cl:16])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 7915Isopropyl AcetateHCID 58018317Nalpha-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-formyl-N-methyl-aminomethyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester

Product 1

HCID 15986103Nalpha-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-methylamino-methyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester.hydrochlorideYield 194.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
10 °C

Procedure

To 61.67 L of 2-propanol, there was added 5.226 kg of Nα-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-formyl-N-methylamino-methyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester to thus form a suspension and the resulting suspension was cooled to 10° C. and stirred in a nitrogen gas stream. Acetyl chloride (10.00 kg) was dropwise added to this suspension over one hour while taking care to prevent any excess generation of heat, then 37.67 L of isopropyl acetate was added to the suspension and the resulting mixture was heated with stirring at 70° C. for 24 hours. After the confirmation of the progress of the reaction by HPLC, the slurry was cooled to 25° C. and stirred over 19 hours. The resulting precipitates were recovered by the filtration using a centrifuge and the resulting cake was washed with 20.90 L of 2-propanol. The resulting wet crystals were dried under reduced pressure at 75° C. to thus give 5.159 kg of the title compound as a white crystalline solid (yield: 95%).

Workup

  1. customto thus form a suspension
  2. temperatureof heat
  3. temperaturethe resulting mixture was heated
  4. stirringwith stirring at 70° C. for 24 hours
  5. customAfter the confirmation of the progress of the reaction by HPLC
  6. temperaturethe slurry was cooled to 25° C.
  7. stirringstirred over 19 hours
  8. customThe resulting precipitates
  9. filtrationwere recovered by the filtration
  10. washthe resulting cake was washed with 20.90 L of 2-propanol

Sources & evidence

ORD record
ord-75e2c72a873646c3aa2cd4fa95c7272f
Source dataset
uspto-grants-2011_11
Patent number
US08058432B2

Reaction notes

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