(r)-3-Pyrrolidin-1-ylmethyl-piperidine → 5-(2,6-Dichloro-phenylmethanesulfonyl)-3-[1-{3,5-dimethyl-4-[3-oxo-3-((s)-3-pyrrolidin-1-ylmethyl-piperidin-1-yl)-propyl]-1h-pyrrol-2-yl}-meth-(z)-ylidene]-1,3-dihydro-indol-2-one

HRID 1359873Notes

Reaction equation

HRID 1359873 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([CH2:30][CH2:31][C:32](O)=[O:33])[C:25]=1[CH3:35])(=[O:12])=[O:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:60]1([CH2:65][C@@H:66]2[CH2:71][CH2:70][CH2:69][NH:68][CH2:67]2)[CH2:64][CH2:63][CH2:62][CH2:61]1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([CH2:30][CH2:31][C:32](=[O:33])[N:68]2[CH2:69][CH2:70][CH2:71][C@@H:66]([CH2:65][N:60]3[CH2:61][CH2:62][CH2:63][CH2:64]3)[CH2:67]2)[C:25]=1[CH3:35])(=[O:11])=[O:12]

Participants

5

Reactant 3

HCID 7183063(r)-3-Pyrrolidin-1-ylmethyl-piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 590776223-{5-[5-(2,6-Dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-propionic Acid

Product 1

HCID 590777615-(2,6-Dichloro-phenylmethanesulfonyl)-3-[1-{3,5-dimethyl-4-[3-oxo-3-((s)-3-pyrrolidin-1-ylmethyl-piperidin-1-yl)-propyl]-1h-pyrrol-2-yl}-meth-(z)-ylidene]-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-{5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-propionic acid (267 mg), HATU (1.2 eq.), (R)-3-pyrrolidin-1-ylmethyl-piperidine (2×) in DMF (2.5 mL) was stirred at rt for 2 hours. The reaction was concentrated, diluted with DCM, washed with water (2×), sodium carbonate (2×), dried and concentrated. The residue was purified on a silica gel column to give 145 mg of the titled compound as a yellow solid.

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with DCM
  3. washwashed with water (2×), sodium carbonate (2×)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-c0e62caaae424c7e85d02cc6e358b786
Source dataset
uspto-grants-2003_07
Patent number
US06599902B2

Reaction notes

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