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

HRID 380809Notes

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 CuI (7 mg) were added and the reaction was heated at 70° C. for 14 h. 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 CuI (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-d0c6673e75174360b463e038772eb718
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06303793B1

Reaction notes

Loading…