Methyl 4-pentynoate → (Z)-5-[2,3-Dihydro-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2-oxo-1H-indol-4-yl]-4-pentynoic acid methyl ester

HRID 366702Notes

Reaction equation

HRID 366702 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][CH2:3][C:4]#[CH:5].[F:9][C:10]1[C:11](I)=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=[O:19])/[C:13]/2=[CH:20]\[C:21]1[NH:22][CH:23]=[CH:24][C:25]=1[O:26][CH3:27]>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>[CH3:8][O:7][C:1](=[O:6])[CH2:2][CH2:3][C:4]#[C:5][C:11]1[C:10]([F:9])=[CH:18][CH:17]=[C:16]2[C:12]=1/[C:13](=[CH:20]/[C:21]1[NH:22][CH:23]=[CH:24][C:25]=1[O:26][CH3:27])/[C:14](=[O:19])[NH:15]2

Participants

6

Reactant 2

HCID 543061Methyl 4-pentynoateHCID 18363902(3Z)-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one2×

Product 1

HCID 20667781(Z)-5-[2,3-Dihydro-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2-oxo-1H-indol-4-yl]-4-pentynoic acid methyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using Method C above, 4-pentynoic acid methyl ester (75.7 mg, 0.68 5 mmol) (see Example 8, supra) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (100 mg, 0.26 mmol) (Starting Material 6, supra) using (Ph3P)4Pd (31.2 mg) and Cul (5.0 mg) as catalyst in DMF (4 mL) and Et3N (4 mL) as solvent at 80° C. for 7 h to yield (Z)-5-[2,3-Dihydro-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2-oxo-1H-indol-4-yl]-4-pentynoic acid methyl ester. (Yield 86 mg, 90%).

Sources & evidence

ORD record
ord-86221430e4454f8d97108e849a49ec03
Source dataset
uspto-grants-2000_10
Patent number
US06130239

Reaction notes

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