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 651087Notes

Reaction equation

HRID 651087 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 2 N NaOH, the solids filtered and washed successively with aqueous 1 N NaOH, EtOAc, aqueous 1 N 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 2 N NaOH, the solids filtered
  3. washwashed successively with aqueous 1 N NaOH, EtOAc, aqueous 1 N HCl, H2O, and ether
  4. filtrationfiltered
  5. customdried
  6. customHPLC (60/40) 2.33 minutes (93%)

Sources & evidence

ORD record
ord-07f635af32234b7b96a53579a6bee7df
Source dataset
uspto-grants-2001_08
Patent number
US06277877B1

Reaction notes

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