(3Z)-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one → HCID 59959937, compound

HRID 366727Notes

Reaction equation

HRID 366727 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]#[CH:9])[CH2:3]1.[F:10][C:11]1[C:12](I)=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])/[C:14]/2=[CH:21]\[C:22]1[NH:23][CH:24]=[CH:25][C:26]=1[O:27][CH3:28]>CN(C=O)C.CCN(CC)CC.CCOC(C)=O.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>[F:10][C:11]1[C:12]([C:9]#[C:8][CH2:7][N:4]2[CH2:5][CH2:6][C@H:2]([OH:1])[CH2:3]2)=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])/[C:14]/2=[CH:21]\[C:22]1[NH:23][CH:24]=[CH:25][C:26]=1[O:27][CH3:28]

Participants

7

Reactant 2

HCID 18363902(3Z)-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one2×HCID 45087249HCID 45087249, compound

Product 1

HCID 59959937HCID 59959937, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Using Method C above, (S)-3-hydroxy-1-prop-2-ynyl-pyrrolidine (60 mg, 0.48 mmol) (Example 96A) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (60 mg, 0.16 mmol) (Starting Material 6) using (Ph3P)4Pd (18 mg, 0.02 mmol) and a catalytic amount of Cul in a mixture of DMF (4 mL) and Et3N (4 mL) as solvent at 80° C. for 6 hrs. Upon completion, the reaction mixture was diluted with EtOAc and extracted with H2O. The organic layer was dried over Na2SO4 and concentrated. (S)-(Z)-1,3-Dihydro-5-fluoro-4-[3-(3-hydroxy-pyrrolidin-1-yl)-1-propynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one was obtained after silica gel column chromatography with a 0-20% MeOH in CH2Cl2 gradient and precipitation out of THF with excess of pentane. (Yield 42 mg, 71%).

Workup

  1. extractionextracted with H2O
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-9bc1e5f0058646ae95e4b495e15616f3
Source dataset
uspto-grants-2000_10
Patent number
US06130239

Reaction notes

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