N-[(5-chloro-1H-indol-2-yl)carbonyl]glycine → 5-Chloro-1H-indole-2-carboxylic acid [2-(Cis-3,4-dihydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide

HRID 1872105Notes

Reaction equation

HRID 1872105 reaction equation
Cl.[OH:2][C@H:3]1[C@@H:7]([OH:8])[CH2:6][NH:5][CH2:4]1.[Cl:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14]([C:19]([NH:21][CH2:22][C:23](O)=[O:24])=[O:20])=[CH:13]2>C(Cl)Cl.CN(C=O)C>[OH:2][C@H:3]1[C@@H:7]([OH:8])[CH2:6][N:5]([C:23](=[O:24])[CH2:22][NH:21][C:19]([C:14]2[NH:15][C:16]3[C:12]([CH:13]=2)=[CH:11][C:10]([Cl:9])=[CH:18][CH:17]=3)=[O:20])[CH2:4]1

Participants

4

Reactant 2

HCID 11436686N-[(5-chloro-1H-indol-2-yl)carbonyl]glycineHCID 21970171(3S,4R)-pyrrolidine-3,4-diol hydrochloride

Product 1

HCID 98407685-Chloro-1H-indole-2-carboxylic acid [2-(Cis-3,4-dihydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

(3R,4S)-3,4-Dihydroxypyrrolidine hydrochloride (the cis, or meso isomer, 1.79 mmol) and [(5-chloro-1H-indole-2-carbonyl)-amino]-acetic acid (0.85 mmol) were coupled according to procedure A (1:1 CH2Cl2 /DMF reaction solvent) with the following workup: the reaction mixture was concentrated, the residue suspended in 10 ml EtOAc and 10 ml 2N NaOH, the solids filtered and washed successively with .aqueous 1N NaOH, EtOAc, aqueous 1N HCl, H2O, and ether. This washing sequence was repeated and the resulting solids were suspended in EtOAc, stirred for 1 hour, filtered and dried: Yield 252 mg, 88%; HPLC (60/40) 2.33 minutes (93%); TSPMS 338/340 (MH+, 100%);

Workup

  1. concentrationthe reaction mixture was concentrated
  2. filtration10 ml 2N NaOH, the solids filtered
  3. washwashed successively with .aqueous 1N NaOH, EtOAc, aqueous 1N HCl, H2O, and ether
  4. filtrationfiltered
  5. customdried
  6. customHPLC (60/40) 2.33 minutes (93%)

Sources & evidence

ORD record
ord-17fb1df7aea64ee7bfda2efa3f91ca36
Source dataset
uspto-grants-2000_08
Patent number
US06107329

Reaction notes

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