Triethylamine → (R)-3-(1H-Indol-3-yl)-2-(5-trimethylsilanylethynyl-thiophene-2-sulfonylamino)-propionic acid

HRID 40494Notes

Reaction equation

Br[C:2]1[S:6][C:5]([S:7]([NH:10][C@H:11]([CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[C:12]([OH:14])=[O:13])(=[O:9])=[O:8])=[CH:4][CH:3]=1.[C:25]([Si:27]([CH3:30])([CH3:29])[CH3:28])#[CH:26].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.[Cu]I>[NH:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]([CH2:15][C@@H:11]([NH:10][S:7]([C:5]2[S:6][C:2]([C:26]#[C:25][Si:27]([CH3:30])([CH3:29])[CH3:28])=[CH:3][CH:4]=2)(=[O:9])=[O:8])[C:12]([OH:14])=[O:13])=[CH:17]1

Participants

Conditions

Temperature: 50 °C

Procedure

In a round bottom flask was added crude compound (R)-2-(5-Bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid product (3) (0.25 g, 0.584 mmol) (synthesized via Example 1, Step A), commercially available ethynyltrimethylsilane (0.17 g, 1.73 mmol), PdCl2P(PPh3)2 (0.041 g, 0.061 mmol), copper(I)iodide (0.006 g, 0.0315 mmol), and triethylamine (0.177 g, 1.75 mmol) dissolved in dry DMF (3 mL) under an atmosphere of nitrogen and mixture heated at 50° C. for two hours. The reaction mixture was then diluted with ethyl acetate and washed with a solution composed of NaCl/NaHCO3/(NH4)2CO3/water (1:1:1:1) (×3), water, brine, and dried (Na2SO4) to give the desired crude (R)-3-(1H-Indol-3-yl)-2-(5-trimethylsilanylethynyl-thiophene-2-sulfonylamino)-propionic acid 8 (185 mg, 71%). LC-MS (ES+) 447; (ES−) 445.

Workup

washwashed with a solution
dry with materialdried (Na2SO4)

Sources & evidence

ORD record: ord-9238cc0fde9c450082e3d9af3b5714a4
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530453B2

Reaction notes

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