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

HRID 1039041Notes

Reaction equation

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

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}-methyl-carbamic acid tert-butyl ester (3.4 g, 7.27 mmol), dichlorobis(benzonitrile)palladium (II) (0.558 g, 1.45 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 purified via flash silica gel chromatography (Analogix IF-280, SF25-40 g column, gradient 90:10-10:90 heptane:EtOAc) to yield tert-butyl 3-(5-(3,4-dimethoxyphenylcarbamoyl)-1H-indol-2-yl)propyl(methyl)carbamate. 1H NMR (300 MHz, CDCl3) δ 7.84 (s, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 6.85 (d, J=8.6 Hz, 1H), 6.32 (s, 1H), 3.93 (s, 3H), 3.89 (s, 3H), 3.31-3.41 (m, 2H), 2.89 (s, 3H), 2.66-2.77 (m, 2H), 1.83-1.94 (m, 2H), and 1.53 (s, 9H). MS (ES+) 468 (M+1).

Workup

concentrationThe resulting mixture was then concentrated in-vacuo
customthe residue purified via flash silica gel chromatography (Analogix IF-280

Sources & evidence

ORD record: ord-9fc2610b66014cc3ac0e7405c32aebaa
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552032B2

Reaction notes

Loading…