5-Chloro-1H-indole-2-carboxylic acid → 3-[(5-chloro-1H-indole-2-carbonyl)-amino]-(2RS)-hydroxy-propionic acid

HRID 480070Notes

Reaction equation

HRID 480070 reaction equation
Cl.C[O:3][C:4](=[O:9])[CH:5]([OH:8])[CH2:6][NH2:7].[Cl:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15]([C:20](O)=[O:21])=[CH:14]2>>[Cl:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15]([C:20]([NH:7][CH2:6][CH:5]([OH:8])[C:4]([OH:3])=[O:9])=[O:21])=[CH:14]2

Participants

3

Reactant 2

HCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 71757671Methyl 3-amino-2-hydroxypropanoate hydrochloride

Product 1

HCID 225938353-[(5-chloro-1H-indole-2-carbonyl)-amino]-(2RS)-hydroxy-propionic acid

Procedure

(RS)-3-amino-2-hydroxypropionic acid methyl ester hydrochloride (6.6 mmol) and 5-chloro-1H-indole-2-carboxylic acid (6.6 mmol) were coupled according to Procedure A (except that acid, then base extraction was performed, and during the first acid wash a precipitate appeared so the mixture was filtered and the filtrate carried on in the usual manner of Procedure A). The crude product (920 mg) was dissolved in methanol and treated with 1 N NaOH (6.6 mL) for 2 hours at 25° C. 1N NaOH was added (6.6 mL) and the mixture was concentrated, the residue dissolved in ethyl acetate, and the resulting solution washed with 2N HCl, brine, dried, and concentrated. The resulting colorless solid was stirred in chloroform and filtered giving the title substance: Yield 763 mg, 40%; HPLC (60/40) 2.86 minutes (89%); mp 214-215° C.; PBMS 283/285 (MH+, 100%);

Workup

  1. extractionbase extraction
  2. washduring the first acid wash a precipitate
  3. filtrationwas filtered
  4. dissolutionThe crude product (920 mg) was dissolved in methanol
  5. additiontreated with 1 N NaOH (6.6 mL) for 2 hours at 25° C
  6. addition1N NaOH was added (6.6 mL)
  7. concentrationthe mixture was concentrated
  8. dissolutionthe residue dissolved in ethyl acetate
  9. washthe resulting solution washed with 2N HCl, brine
  10. customdried
  11. concentrationconcentrated
  12. filtrationfiltered
  13. customgiving the title substance

Sources & evidence

ORD record
ord-d57e2aac43444b65aa638e88ff501583
Source dataset
uspto-grants-2003_11
Patent number
US06649634B2

Reaction notes

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