Chlorotrimethylsilane → (Z)-1,3-dihydro-4-(5-hydroxy-1-pentynyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one

HRID 380808Notes

Reaction equation

HRID 380808 reaction equation
[CH2:1]([OH:6])[CH2:2][CH2:3][C:4]#[CH:5].Cl[Si](C)(C)C.Br[C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1/[C:15](=[CH:23]/[C:24]1[NH:25][CH:26]=[CH:27][C:28]=1[O:29][CH3:30])/[C:16](=[O:22])[NH:17]2>CN(C=O)C.C(N(CC)CC)C>[OH:6][CH2:1][CH2:2][CH2:3][C:4]#[C:5][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1/[C:15](=[CH:23]/[C:24]1[NH:25][CH:26]=[CH:27][C:28]=1[O:29][CH3:30])/[C:16](=[O:22])[NH:17]2

Participants

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 793464-Pentyn-1-olHCID 18359254(Z)-4-bromo-1,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one2×

Product 1

HCID 59959882(Z)-1,3-dihydro-4-(5-hydroxy-1-pentynyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

Using Method I above, 4-pentyn-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) (Aldrich). 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 (15 mg) (Aldrich) and CuI (7 mg) (Aldrich) were added and the reaction was heated at 70° C. for 14 h. The reaction mixture was then poured into 25 mL 1N HCl and the yellow precipitate was filtered off. The product was purified via flash column chromatography to obtain (Z)-1,3-dihydro-4-(5-hydroxy-1-pentynyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one as a yellow powder. (Yield 55 mg, 45%).

Workup

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

Sources & evidence

ORD record
ord-9b12b2dfb0634a3ab212e811d27006c2
Source dataset
uspto-grants-2001_10
Patent number
US06303793B1

Reaction notes

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