Indomethacin → tert-Butyl 3-[2-{1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl}acetamido]propylcarbamate

HRID 16660

Reaction equation

HRID 16660 reaction equation
[CH3:1][C:2]1[N:10]([C:11]([C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)=[O:12])[C:9]2[CH:8]=[CH:7][C:6]([O:20][CH3:21])=[CH:5][C:4]=2[C:3]=1[CH2:22][C:23]([OH:25])=O.[C:26]([O:30][C:31](=[O:37])[NH:32][CH2:33][CH2:34][CH2:35][NH2:36])([CH3:29])([CH3:28])[CH3:27].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([C:11]([N:10]2[C:9]3[C:4](=[CH:5][C:6]([O:20][CH3:21])=[CH:7][CH:8]=3)[C:3]([CH2:22][C:23]([NH:36][CH2:35][CH2:34][CH2:33][NH:32][C:31](=[O:37])[O:30][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:25])=[C:2]2[CH3:1])=[O:12])=[CH:18][CH:17]=1

Participants

7

Reactant 5

HCID 3715IndomethacinHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2735700tert-Butyl (3-aminopropyl)carbamate

Product 1

HCID 69315841tert-Butyl 3-[2-{1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl}acetamido]propylcarbamateYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

an Indo-Coumarinyl Analog: Compound 27gg, N-[3-{7-(N,N-Diethylamino)coumarin-3-carboxylamido}butyl]-2-{1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl}acetamide was synthesized by the method depicted in FIG. 8. Briefly, indomethacin was complexed with tert-Butyl-3-aminopropylcarbamate for 16 hours at room temperature in the presence of 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDCl), 1-hydroxybenzotriazole (HOBt), N,N-diisopropylethylamine (DIPEA), and N,N-dimethylformamide (DMF). tert-Butyl 3-[2-{1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl}acetamido]propylcarbamate was produced as a pale yellow solid at 70% yield. This product was then dissolved in dichloromethane and treated with HCl (gas) for 2 hours at room temperature, producing N-(4-qminobutyl)-2-{1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl}acetamide hydrochloride as a brown solid with a yield of 98%, which was reacted with triethylamine (TEA) in dimethyl sulfoxide (DMSO) for 5 minutes at room temperature prior to the addition of 7-(N,N-Diethylamino)coumarin-3-carboxylic acid succinimidyl ester. The reaction proceeded for 16 hours at room temperature and produced Compound 27gg as a yellow solid (66% yield).

Sources & evidence

ORD record
ord-27fc7749abee4c409b09248c401d0d6e
Source dataset
uspto-grants-2010_06
Patent number
US07736624B2

Linked notes

Loading…