Triethylamine → 3-[1-[4-((r)-2-Cyclopropylaminomethyl-pyrrolidin-1-carbonyl)-3,5-dimethyl-1h-pyrrol-2-yl]-meth-(z)-ylidene]-5-(2,6-dichlorophenylmethanesulfonyl)-1,3-dihydro-indol-2-one

HRID 1359701Notes

Reaction equation

HRID 1359701 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]([C:30](O)=[O:31])[C:25]=1[CH3:33])(=[O:12])=[O:11].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[CH:62]1([NH:65][CH2:66][C@H:67]2[CH2:71][CH2:70][CH2:69][NH:68]2)[CH2:64][CH2:63]1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH:62]1([NH:65][CH2:66][C@H:67]2[CH2:71][CH2:70][CH2:69][N:68]2[C:30]([C:26]2[C:25]([CH3:33])=[C:24](/[CH:23]=[C:16]3\[C:17](=[O:22])[NH:18][C:19]4[C:15]\3=[CH:14][C:13]([S:10]([CH2:9][C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])(=[O:11])=[O:12])=[CH:21][CH:20]=4)[NH:28][C:27]=2[CH3:29])=[O:31])[CH2:64][CH2:63]1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 590775075-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acidHCID 69627816HCID 69627816, compound

Product 1

HCID 590776203-[1-[4-((r)-2-Cyclopropylaminomethyl-pyrrolidin-1-carbonyl)-3,5-dimethyl-1h-pyrrol-2-yl]-meth-(z)-ylidene]-5-(2,6-dichlorophenylmethanesulfonyl)-1,3-dihydro-indol-2-oneYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-[5-(2,6-dichlorophenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (100 mg, 0.2 mmol), EDAC (76 mg, 2 eq.), HOBt (27 mg, 1 eq.) in DMF (4 mL) was added triethyamine (0.08 mL, 0.57 mmol) and cyclopropyl-(R)-1-pyrrolidin-2-ylmethyl-amine (0.05 mL). After stirring at rt for 18 h, the reaction was basified with sodium bicarbonate, followed by extraction with 5% of methanol in dichloromethane. After concentration, the residue was purified on a silica gel column eluting with 5% of methanol in dichloromethane to give 80 mg (64%) of the titled compound.

Workup

  1. extractionfollowed by extraction with 5% of methanol in dichloromethane
  2. concentrationAfter concentration
  3. customthe residue was purified on a silica gel column
  4. washeluting with 5% of methanol in dichloromethane

Sources & evidence

ORD record
ord-57a29d5bb78544a0962dafb29c24c8f4
Source dataset
uspto-grants-2003_07
Patent number
US06599902B2

Reaction notes

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