(Z)-3-[(4-Acetyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-5-fluoro-4-iodo-2H-indol-2-one → rac-(Z)-3-[(4-Acetyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-5-fluoro-4-[(3-hydroxy-pyrrolidin-3-yl)ethynyl]-2H-indol-2-one

HRID 1069750Notes

Reaction equation

HRID 1069750 reaction equation
[OH:1][C:2]1([C:7]#[CH:8])[CH2:6][CH2:5][NH:4][CH2:3]1.[C:9]([C:12]1[CH:13]=[C:14](/[CH:17]=[C:18]2\[C:19](=[O:29])[NH:20][C:21]3[C:26]\2=[C:25](I)[C:24]([F:28])=[CH:23][CH:22]=3)[NH:15][CH:16]=1)(=[O:11])[CH3:10]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C.CCN(CC)CC>[C:9]([C:12]1[CH:13]=[C:14](/[CH:17]=[C:18]2\[C:19](=[O:29])[NH:20][C:21]3[C:26]\2=[C:25]([C:8]#[C:7][C:2]2([OH:1])[CH2:6][CH2:5][NH:4][CH2:3]2)[C:24]([F:28])=[CH:23][CH:22]=3)[NH:15][CH:16]=1)(=[O:11])[CH3:10]

Participants

6

Reactant 2

HCID 18366029(Z)-3-[(4-Acetyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-5-fluoro-4-iodo-2H-indol-2-oneHCID 183660713-Ethynylpyrrolidin-3-ol

Product 1

HCID 18366126rac-(Z)-3-[(4-Acetyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-5-fluoro-4-[(3-hydroxy-pyrrolidin-3-yl)ethynyl]-2H-indol-2-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using Method C above, rac-3-hydroxy-3-ethynyl-pyrrolidine (35.1 mg, 0.32 mmol) (Example 97C) was coupled with (Z)-3-[(4-acetyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-5-fluoro-4-iodo-2H-indol-2-one (50 mg, 0.13 mmol) (see Example 90B) using (Ph3P)4Pd (15 mg) and Cul (3.0 mg) as catalyst in DMF (3 mL) and Et3N (3 mL) as solvent at 85° C. for 5 h. (Yield 10 mg, 21%).

Sources & evidence

ORD record
ord-978171d94e2244a096ef21f0515bbb46
Source dataset
uspto-grants-2001_06
Patent number
US06252086B1

Reaction notes

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