1,1'-Carbonyldiimidazole → N-(2,6-dichlorobenzoyl)-4-[2-[N-(methanesulfonyl)carbamoyl]phenyl]-L-phenylalanine methyl ester

HRID 1060423Notes

Reaction equation

HRID 1060423 reaction equation
[CH3:1][O:2][C:3](=[O:32])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29](O)=[O:30])=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:45][S:46]([NH2:49])(=[O:48])=[O:47].C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:32])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29](=[O:30])[NH:49][S:46]([CH3:45])(=[O:48])=[O:47])=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 53640164N-(2,6-dichlorobenzoyl)-4-(2-carboxyphenyl)-L-phenylalanine methyl ester

Product 1

HCID 53805245N-(2,6-dichlorobenzoyl)-4-[2-[N-(methanesulfonyl)carbamoyl]phenyl]-L-phenylalanine methyl esterYield 55.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-(2,6-Dichlorobenzoyl)-4-(2-carboxyphenyl)-L-phenylalanine methyl ester (57.0 mg) was dissolved in anhydrous THF (1 mL), carbonyldiimidazole (23.5 mg) was added and the mixture was stirred at room temperature under N2 for 2 h. Methanesulfonamide (17.2 mg) and DBU (27 μL) were added and the mixture was stirred for an additional 18 h. The mixture was then heated to 40° C., stirred for 7 h at the same temperature, cooled to room temperature, diluted with EtOAc, washed with 1N HCl and then brine, dried (MgSO4) and evaporated. The residue was purified by preparative TLC (silica gel) using CH2Cl2/MeOH (100:1 to 10:1) as an eluent to give N-(2,6-dichlorobenzoyl)-4-[2-[N-(methanesulfonyl)carbamoyl]phenyl]-L-phenylalanine methyl ester (37.0 mg). ESMS: m/z 549 (MH+).

Workup

  1. stirringthe mixture was stirred for an additional 18 h
  2. temperatureThe mixture was then heated to 40° C.
  3. stirringstirred for 7 h at the same temperature
  4. temperaturecooled to room temperature
  5. washwashed with 1N HCl
  6. dry with materialbrine, dried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by preparative TLC (silica gel)

Sources & evidence

ORD record
ord-60a6097349d54aa588c5481023a698cb
Source dataset
uspto-grants-2003_02
Patent number
US06521666B1

Reaction notes

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