Methyl isothiocyanate → N-[2-chloro-4-(3-methylthioureido)benzoyl]-4-(2-methoxyphenyl)-L-phenylalanine methyl ester

HRID 1060426Notes

Reaction equation

[CH3:1][N:2]=[C:3]=[S:4].[CH3:5][O:6][C:7](=[O:35])[C@H:8]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH3:34])=[CH:23][CH:22]=1)[NH:9][C:10](=[O:19])[C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][C:12]=1[Cl:18].CCN(C(C)C)C(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH3:5][O:6][C:7](=[O:35])[C@H:8]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH3:34])=[CH:23][CH:22]=1)[NH:9][C:10](=[O:19])[C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:3]([NH:2][CH3:1])=[S:4])=[CH:13][C:12]=1[Cl:18]

Participants

Conditions

Temperature: 90 °C

Procedure

Methylisothiocyanate (43 μL) was added to a solution of N-(4-amino-2-chlorobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester (55.1 mg) in anhydrous DMF (1 mL) containing DIEA (22 μL) and DMAP (catalitic amount). The resulting mixture was then heated at 90° C. under N2 for 1 d. After cooling, the mixture was diluted with EtOAc, washed sequentially with 1N HCl, satd. NaHCO3 and water, dried (MgSO4) and evaporated. The residue was purified by preparative TLC (silica gel) using CH2Cl2/MeOH (15:1) as an eluent to give N-[2-chloro-4-(3-methylthioureido)benzoyl]-4-(2-methoxyphenyl)-L-phenylalanine methyl ester (22.7 mg). ESMS: m/z 512 (MH+).

Workup

temperatureAfter cooling
washwashed sequentially with 1N HCl
dry with materialNaHCO3 and water, dried (MgSO4)
customevaporated
customThe residue was purified by preparative TLC (silica gel)

Sources & evidence

ORD record: ord-358f1c936d364d5e8ed4ccaf1863b67c
Source dataset: uspto-grants-2003_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06521666B1

Reaction notes

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