(S)-tert-butyl 1-phenylbut-3-yn-2-ylcarbamate → tert-butyl(S)-4-(3-(isoquinolin-6-yl)isoxazol-5-yl)-1-phenylbut-3-yn-2-ylcarbamate

HRID 598850Notes

Reaction equation

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

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of (S)-tert-butyl 1-phenylbut-3-yn-2-ylcarbamate (0.16 g, 0.65 mmol) in 6 mL of Et3N in a sealable tube were added 6-(5-iodoisoxazol-3-yl)isoquinoline (0.18 g, 0.54 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.019 g, 0.027 mmol), and copper(I) iodide (0.016 g, 0.082 mmol). The tube was sealed and heated to 65° C. for 12 hours. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel, affording tert-butyl(S)-4-(3-(isoquinolin-6-yl)isoxazol-5-yl)-1-phenylbut-3-yn-2-ylcarbamate (0.12 g, 50% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 9.30 (s, 1H), 8.63-8.57 (m, 1H), 8.20-8.17 (m, 1H), 8.09-8.03 (m, 2H), 7.73-7.69 (m, 1H), 7.39-7.27 (m, 5H), 6.81 (s, 1H), 5.05-4.94 (m, 1H), 4.86-4.74 (m, 1H), 3.17-3.03 (m, 2H), 1.46 (s, 9H).

Workup

customThe tube was sealed
customThe solvent was removed under reduced pressure
customthe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record: ord-5eeac4b5fb5d4910bfc31c0ab4729e50
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897619B2

Reaction notes

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