(3Z)-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one → HCID 5288222, compound

HRID 380905Notes

Reaction equation

HRID 380905 reaction equation
[F:1][C:2]1[C:3](I)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:14][CH:15]=[CH:16][C:17]=1[O:18][CH3:19].F[C:22](F)(F)[C:23]([OH:25])=O.C(Cl)Cl>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.[Cu]I.CN(C=O)C.CCN(CC)CC.C(Cl)Cl.O>[NH2:14][C@@H:13]([C@H:23]([OH:25])[CH3:22])[C@H:17]([OH:18])[C:16]#[C:15][C:3]1[C:2]([F:1])=[CH:10][CH:9]=[C:8]2[C:4]=1/[C:5](=[CH:12]/[C:13]1[NH:14][CH:15]=[CH:16][C:17]=1[O:18][CH3:19])/[C:6](=[O:11])[NH:7]2

Participants

9

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 21863450Trifluoroacetic acid methylene chloride

Product 1

HCID 5288222HCID 5288222, compound

Reagents, catalysts & solvents 6

HCID 962WaterCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

Using Method C above, 4R-(1R-Hydroxy-prop-2-ynyl)-2,2,5R-trimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (0.2 g, 0.65 mmol) (Example 105A above) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (0.1 g, 0.26 mmol) (Starting Material 6) using (Ph3P)4Pd (30 mg) and CuI (6 mg) as catalyst in DMF (5 mL) and Et3N (5 mL) as solvent at 85° C. for 18 h. To above compound in CH2Cl2 (10 mL) was added a 1:1 mixture of trifLuoroacetic acid/CH2Cl2 (10 mL) and 5 drops of water at 0° C. and the mixture was stirred at 0° C. for 1.5 h. The mixture was then quenched with conc. NH4OH (10 mL) and diluted with EtOAc. The organic Layer was washed with brine and dried with MgSO4. The product was purified via flash column chromatography (10% MeOH in CH2Cl2). (Yield 35 mg, 35%).

Workup

  1. customThe mixture was then quenched with conc. NH4OH (10 mL)
  2. additiondiluted with EtOAc
  3. washThe organic Layer was washed with brine
  4. dry with materialdried with MgSO4
  5. customThe product was purified via flash column chromatography (10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-f0cdccf9113a4a238080775c8f47cd7f
Source dataset
uspto-grants-2001_10
Patent number
US06303793B1

Reaction notes

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