Chlorotrimethylsilane → (Z)-1,3-dihydro-4-(4-hydroxy-1-butynyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one

HRID 1069664Notes

Reaction equation

[CH2:1]([OH:5])[CH2:2][C:3]#[CH:4].Cl[Si](C)(C)C.Br[C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1/[C:14](=[CH:22]/[C:23]1[NH:24][CH:25]=[CH:26][C:27]=1[O:28][CH3:29])/[C:15](=[O:21])[NH:16]2>CN(C=O)C.C(N(CC)CC)C>[OH:5][CH2:1][CH2:2][C:3]#[C:4][C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1/[C:14](=[CH:22]/[C:23]1[NH:24][CH:25]=[CH:26][C:27]=1[O:28][CH3:29])/[C:15](=[O:21])[NH:16]2

Participants

Conditions

Temperature: 70 °C

Procedure

Using Method I above, 3-butyn-1-ol (40 mg, 0.57 mmol) (Aldrich) was dissolved, under argon, in 3 mL DMF and 2 mL triethylamine, and to this solution was added chlorotrimethylsilane (0.13 mL, 1 mmol). The reaction was stirred at room temperature for 1 h, at which time (Z)-4-bromo-1,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (110 mg, 0.38 mmol) (Starting Material 1 supra) was added and the solution was degassed for 15 min by bubbling argon through the solution. (Ph3P)2PdCl2 (13 mg) and Cul (7 mg) were added and the reaction was heated at 70° C. for 14h. The reaction mixture was then poured into 25 mL 1 N HCl and the yellow precipitate was filtered off. The product was purified via flash column chromatography to obtain (Z)-1,3-dihydro-4-(4-hydroxy-1-butynyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one as a yellow powder. (Yield 35 mg, 30%).

Workup

additionwas added
customthe solution was degassed for 15 min
customby bubbling argon through the solution
addition(Ph3P)2PdCl2 (13 mg) and Cul (7 mg) were added
additionThe reaction mixture was then poured into 25 mL 1 N HCl
filtrationthe yellow precipitate was filtered off
customThe product was purified via flash column chromatography

Sources & evidence

ORD record: ord-8d17c4474094496f9271b5ff531a2eae
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06252086B1

Reaction notes

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