{5-[2-Amino-5-(3,4-dimethoxy-phenylcarbamoyl)-phenyl]-pent-4-ynyl}-carbamic acid tert-butyl ester → tert-butyl 3-(5-(3,4-dimethoxyphenylcarbamoyl)-1H-indol-2-yl)propylcarbamate

HRID 1039037Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A 500 mL round bottom flask was charged with {5-[2-amino-5-(3,4-dimethoxy-phenylcarbamoyl)-phenyl]-pent-4-ynyl}-carbamic acid tert-butyl ester (3.0 g, 6.62 mmol), dichlorobis(benzonitrile)palladium (II) (0.514 g, 1.34 mmol), and dimethylformamide (80 mL) and the resulting mixture heated to 80° C. for 24 h. The resulting mixture was then concentrated in-vacuo and the residue via flash silica gel chromatography (Analogix IF-280, SF25-40 g column, gradient 100:0-90:10 CH2Cl2:MeOH) to yield tert-butyl 3-(5-(3,4-dimethoxyphenylcarbamoyl)-1H-indol-2-yl)propylcarbamate. MS (ES+) 454 (M+1); HPLC: Kromasil C18 column (50×2 mm; 3.5μ), gradient 1{tilde over (0)}90% (MeCN+0.16% TFA) in (water+0.2% TFA) over 4 min, tR=3.78 min.

Workup

concentrationThe resulting mixture was then concentrated in-vacuo

Sources & evidence

ORD record: ord-5800590222ee4b3f894d694369453307
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552032B2

Reaction notes

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