Hydrochloric Acid → HCID 10810696, compound

HRID 1901795Notes

Reaction equation

HRID 1901795 reaction equation
C([O:3][C:4](=[O:31])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]([CH3:25])=[C:12]2[CH2:26][C:27]([NH:29][NH2:30])=[O:28])C.[OH-].[Na+].Cl>CCO.C1COCC1.O>[NH:29]([C:27](=[O:28])[CH2:26][C:12]1[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:31])=[O:3])[CH:10]=2)[N:14]([CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:13]=1[CH3:25])[NH2:30]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 10836052HCID 10836052, compound

Product 1

HCID 10810696HCID 10810696, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 310 mg (1 mmol) of 5-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid hydrazide (Example 62) in 25 mL of DMSO was treated with 45 mg (1.1 mmol) of 60% NaH/mineral oil and after 0.25 hours, 0.16 mL (1.1 mmol) of ethyl 4-bromobutyrate was added. The mixture was stirred for 4 hours, diluted with water and extracted with EtOAc. The EtOAc solution was washed with NaCl solution, dried (Na2SO4), and concentrated at reduced pressure. The residue was chromatographed on silica eluting with CH2Cl2 →4% MeOH/CH2C2, to give 290 mg (68% yield) of 4-[[3-(2-hydrazino-2-oxoethyl)-2-methyl-1-(phenylmethyl)-1H-indole-5-yl]oxy]butanoic acid ethyl ester. This ester (0.685 mmol) and 2 mL of 2N NaOH in 25 mL of EtOH and 5 mL of THF was stirred for 22.5 hours. The mixture was diluted with water, made acidic to pH 6 with 1N HCl and extracted with EtOAc, the EtOAc dried (Na2SO4), and concentrated at reduced pressure. The residue was dissolved in EtOH and precipitated with ether to give 50 mg (47% yield) of 4-[[3-(2-hydrazino-2-oxoethyl)-2-methyl-1-(phenylmethyl)-1H-indole-5-yl]oxy]butanoic acid, mp, 160° C. (decomposition).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialthe EtOAc dried (Na2SO4)
  3. concentrationconcentrated at reduced pressure
  4. dissolutionThe residue was dissolved in EtOH
  5. customprecipitated with ether

Sources & evidence

ORD record
ord-4026052065654323bb892761d50a2840
Source dataset
uspto-grants-1996_11
Patent number
US05578634

Reaction notes

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