4-(2-Propyn-1-yl)morpholine → (Z)-1,3-dihydro-5-fluoro-3-[(4-methyl-1H-imidazol-5-yl)methylene]-4-[3-(4-morpholinyl)-1-propynyl]-2H-indol-2-one

HRID 366680Notes

Reaction equation

HRID 366680 reaction equation
[N:1]1([CH2:7][C:8]#[CH:9])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]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:26][CH:25]=[N:24][C:23]=1[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>[F:10][C:11]1[C:12]([C:9]#[C:8][CH2:7][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]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:26][CH:25]=[N:24][C:23]=1[CH3:27]

Participants

6

Reactant 2

HCID 4129414-(2-Propyn-1-yl)morpholineHCID 178433242HCID 178433242, compound2×

Product 1

HCID 178433237(Z)-1,3-dihydro-5-fluoro-3-[(4-methyl-1H-imidazol-5-yl)methylene]-4-[3-(4-morpholinyl)-1-propynyl]-2H-indol-2-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using Method C above, 3-(4-morpholinyl)-1-propyne (63.6 mg, 0.51 mmol) (prepared according to H. Kano et al., J. Med. Chem. 10:411-418 (1967)) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(4-methyl-1H-imidazol-5-yl) methylene]-2H-indol-2-one (75 mg, 0.203 mmol) (Starting Material 3 supra) using (Ph3P)4Pd (23.5 mg) and Cul (4 mg) as catalyst in DMF (3 mL) and Et3N (3 mL) as solvent at 80° C. for 18 h to give (Z)-1,3-dihydro-5-fluoro-3-[(4-methyl-1H-imidazol-5-yl)methylene]-4-[3-(4-morpholinyl)-1-propynyl]-2H-indol-2-one. (Yield 40 mg, 54%).

Sources & evidence

ORD record
ord-9a13da959a96461cbcd20274df1f9a4b
Source dataset
uspto-grants-2000_10
Patent number
US06130239

Reaction notes

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