Diisopropylethylamine → (Z)-N-[2-[[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]phenyl]amino]-2-oxoethyl]-4-(fluorosulfonyl)benzamide

HRID 382042Notes

Reaction equation

HRID 382042 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2/[C:10](=[CH:18]/[C:19]2[NH:20][CH:21]=[CH:22][CH:23]=2)/[C:11](=[O:17])[NH:12]3)[CH:5]=[CH:6][CH:7]=1.[F:24][S:25]([C:28]1[CH:40]=[CH:39][C:31]([C:32]([NH:34][CH2:35][C:36](O)=[O:37])=[O:33])=[CH:30][CH:29]=1)(=[O:27])=[O:26].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[O:17]=[C:11]1[NH:12][C:13]2[C:9](/[C:10]/1=[CH:18]/[C:19]1[NH:20][CH:21]=[CH:22][CH:23]=1)=[C:8]([C:4]1[CH:3]=[C:2]([NH:1][C:36](=[O:37])[CH2:35][NH:34][C:32](=[O:33])[C:31]3[CH:30]=[CH:29][C:28]([S:25]([F:24])(=[O:27])=[O:26])=[CH:40][CH:39]=3)[CH:7]=[CH:6][CH:5]=1)[CH:16]=[CH:15][CH:14]=2

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 9819193(Z)-4-(3-aminophenyl)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-oneHCID 183638592-{[4-(Fluorosulfonyl)phenyl]formamido}acetic acid

Product 1

HCID 59971433(Z)-N-[2-[[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]phenyl]amino]-2-oxoethyl]-4-(fluorosulfonyl)benzamideYield 24%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (Z)-4-(3-aminophenyl)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one (30 mg, 0.100 mmol) (from Example 4 supra), crude (4-fluorosulfonyl-benzoylamino)-acetic acid (28 mg, 0.107 mmol) (from step B above), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 45 mg, 0.119 mmol) (Advance ChemTech), 1-hydroxybenzotriazole hydrate (HOBT, 16 mg, 0.118 mmol) (Aldrich), and N,N-diisopropylethylamine (52 μL, 0.300 mmol) (Aldrich) in 3 mL of dry N,N-dimethylformamide (Fisher Scientific) was stirred at 50° C. under a nitrogen atmosphere for 7 h then stirred at room temperature under a nitrogen atmosphere for 12 h. The reaction mixture was diluted with 40 mL ethyl acetate and washed with distilled water. The organic phase was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 40% acetone-hexanes then 70% acetone-hexanes elution) provided pure (Z)-N-[2-[[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]phenyl]amino]-2-oxoethyl]-4-(fluorosulfonyl)benzamide (yield: 13 mg, 24%) as a yellow solid (mp 248-250° C.).

Workup

  1. washwashed with distilled water
  2. concentrationThe organic phase was concentrated in vacuo
  3. washFlash chromatography (Merck Silica gel 60, 230-400 mesh, 40% acetone-hexanes then 70% acetone-hexanes elution)

Sources & evidence

ORD record
ord-5c969d28323e4a879ddebce156cbc5fb
Source dataset
uspto-grants-2001_10
Patent number
US06307056B1

Reaction notes

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