Acetonitrile → Nalpha-(2,6-dichlorobenzoyl)-4-{2-ethoxycarbonylamino-5-(N-formyl-N-methyl-aminomethyl)-benzoylamino}-L-phenylalanine isopropyl ester

HRID 557458Notes

Reaction equation

HRID 557458 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]([CH:14]=[O:15])[CH3:13])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(#N)C.Cl[C:20]([O:22][CH2:23][CH3:24])=[O:21].[CH:25]([O:28][C:29](=[O:50])[C@H:30]([CH2:42][C:43]1[CH:48]=[CH:47][C:46]([NH2:49])=[CH:45][CH:44]=1)[NH:31][C:32](=[O:41])[C:33]1[C:38]([Cl:39])=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:40])([CH3:27])[CH3:26]>CC(O)C.N1C=CC=CC=1>[CH:25]([O:28][C:29](=[O:50])[C@H:30]([CH2:42][C:43]1[CH:44]=[CH:45][C:46]([NH:49][C:4](=[O:6])[C:3]2[CH:7]=[C:8]([CH2:11][N:12]([CH:14]=[O:15])[CH3:13])[CH:9]=[CH:10][C:2]=2[NH:1][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:47][CH:48]=1)[NH:31][C:32](=[O:41])[C:33]1[C:34]([Cl:40])=[CH:35][CH:36]=[CH:37][C:38]=1[Cl:39])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10928Ethyl chloroformate2×HCID 580183122-amino-5-(N-formyl-N-methylamino-methyl)benzoic acidHCID 580183184-Amino-N-(2,6-dichlorobenzoyl)-L-phenylalanine Isopropylester

Product 1

HCID 25134446Nalpha-(2,6-dichlorobenzoyl)-4-{2-ethoxycarbonylamino-5-(N-formyl-N-methyl-aminomethyl)-benzoylamino}-L-phenylalanine isopropyl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 3776IsopropanolSolvent2×

Conditions

Temperature
10 °C

Procedure

To 2.0 g of 2-amino-5-(N-formyl-N-methylamino-methyl)-benzoic acid, there were added 10 mL of acetonitrile and 3.9 mL of pyridine to form a slurry and the latter was cooled to 10° C. To this slurry, there was dropwise added 2.76 mL of ethyl chloro-formate over 5 minutes and then stirred for one hour. After the confirmation of the disappearance of the starting material by HPLC, 1.46 mL of 2-propanol was added to the reaction liquid so that the unreacted ethyl chloroformate was thus decomposed at 25° C. To this reaction liquid, there was added 3.80 g of 4-amino-Nα-(2,6-dichlorobenzoyl)-L-phenylalanine isopropyl ester and the resulting mixture was stirred overnight. Subsequently, 30 mL of 2-propanol was dropwise added to the mixture, followed by the stirring of the mixture at 10° C. for 3 hours. The solid separated was isolated through filtration under reduced pressure, washed with 10 mL of 2-propanol and then dried at 60° C. for 18 hours under reduced pressure to thus give 4.35 g of the intended product as a white crystalline solid.

Workup

  1. customto form a slurry
  2. customover 5 minutes
  3. customwas thus decomposed at 25° C
  4. customTo this reaction liquid, there
  5. stirringthe resulting mixture was stirred overnight
  6. stirringstirring of the mixture at 10° C. for 3 hours
  7. customThe solid separated
  8. customwas isolated through filtration under reduced pressure
  9. washwashed with 10 mL of 2-propanol
  10. dry with materialdried at 60° C. for 18 hours under reduced pressure to thus give 4.35 g of the intended product as a white crystalline solid

Sources & evidence

ORD record
ord-e0faa566c4954635a640f0ddb5aff04d
Source dataset
uspto-grants-2011_11
Patent number
US08058432B2

Reaction notes

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