1,2-Dichloroethane → 3-[1-[4-((2r,3 s)-2-Cyclopropylaminomethyl-3-hydroxy-pyrrolidine-1-carbonyl)-3,5-dimethyl-1h-pyrrol-2-yl]-meth-(z)-ylidene]-5-(2,6-dichloro-phenylmethanesulfonyl)-1,3-dihydro-indol-2-one

HRID 1359839Notes

Reaction equation

HRID 1359839 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]([OH:32])=O)[C:25]=1[CH3:33])(=[O:12])=[O:11].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH:48]1([NH:51][CH2:52][C@@H:53]2[C@@H:57]([OH:58])[CH2:56][CH2:55][NH:54]2)[CH2:50][CH2:49]1>CN(C=O)C>[CH:48]1([NH:51][CH2:52][C@@H:53]2[C@@H:57]([OH:58])[CH2:56][CH2:55][N:54]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:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])(=[O:12])=[O:11])=[CH:21][CH:20]=4)[NH:28][C:27]=2[CH3:29])=[O:32])[CH2:50][CH2:49]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 590775075-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acidHCID 69869847(2R,3S)-2-cyclopropylaminomethyl-pyrrolidin-3-ol

Product 1

HCID 590776673-[1-[4-((2r,3 s)-2-Cyclopropylaminomethyl-3-hydroxy-pyrrolidine-1-carbonyl)-3,5-dimethyl-1h-pyrrol-2-yl]-meth-(z)-ylidene]-5-(2,6-dichloro-phenylmethanesulfonyl)-1,3-dihydro-indol-2-oneYield 31.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (250 mg, 0.5 mmol), HOBt (81 mg, 1.2 eq.), EDC (115 mg, 1.2 eq.), TEA (0.17 mL, 2.5 eq.) and (2R,3S)-2-cyclopropylaminomethyl-pyrrolidin-3-ol (312 mg, 4 eq.) in DMF (10 mL) was stirred at rt for overnight. The reaction was concentrated, washed with water, sodium bicarbonate and brine, dried and concentrated. The residue was purified on a silica gel column to give 100 mg of the titled compound as a yellow solid.

Workup

  1. concentrationThe reaction was concentrated
  2. washwashed with water, sodium bicarbonate and brine
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-6f4a964057424e1bb74aac382ec815a1
Source dataset
uspto-grants-2003_07
Patent number
US06599902B2

Reaction notes

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