N-[5-(2-aminophenyl)pent-4-ynyl]-2-(S)-(2,2,2-trifluoroacetylamino)butyramide → (S)-N-(3-(1H-indol-2-yl)propyl)-2-(2,2,2-trifluoroacetamido)butanamide

HRID 1039021Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A 50 mL round bottom flask was charged with N-[5-(2-aminophenyl)pent-4-ynyl]-2-(S)-(2,2,2-trifluoroacetylamino)butyramide (130 mg, 0.37 mmol), dichlorobis(benzonitrile)palladium (II) (38.0 mg, 0.099 mmol), and dimethylformamide (4.1 mL) and the resulting mixture heated to 80° C. for 22 h. The resulting mixture was then concentrated in-vacuo and the resulting residue purified via flash silica gel chromatography (Analogix IF-280, SF25-40 g column, gradient 90:10-50:50 Heptane:EtOAc) to yield (S)—N-(3-(1H-indol-2-yl)propyl)-2-(2,2,2-trifluoroacetamido)butanamide. 1H NMR (300 MHz, CDCl3) δ 7.48-7.53 (m, 1H), 7.32 (d, J=7.9 Hz, 1H), 7.04-7.15 (m, 2H), 6.23 (s, 1H), 4.32-4.39 (m, 1H), 3.31-3.38 (m, 2H), 2.71-2.75 (m, 2H), 1.82-1.95 (m, 3H), 1.63-1.77 (m, 1H), and 0.90-0.95 (m, 3H); MS (ES+) 356 (M+1).

Workup

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

Sources & evidence

ORD record: ord-76682158696840d2900fab838c7b34dc
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552032B2

Reaction notes

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