Sodium hydride → HCID 10836052, compound

HRID 1901794Notes

Reaction equation

HRID 1901794 reaction equation
[CH3:1][C:2]1[N:3]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:4]2[C:9]([C:10]=1[CH2:11][C:12]([NH:14][NH2:15])=[O:13])=[CH:8][C:7]([O:16]CC1C=CC3C(=CC=CC=3)N=1)=[CH:6][CH:5]=2.[H-].[Na+].Br[CH2:38][CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>CS(C)=O.O>[CH2:44]([O:43][C:41](=[O:42])[CH2:40][CH2:39][CH2:38][O:16][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:2]([CH3:1])=[C:10]2[CH2:11][C:12]([NH:14][NH2:15])=[O:13])[CH3:45]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 76300Ethyl 4-bromobutyrateHCID 70339518HCID 70339518, compound

Product 1

HCID 10836052HCID 10836052, compoundYield 68.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

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. washThe EtOAc solution was washed with NaCl solution
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was chromatographed on silica eluting with CH2Cl2 →4% MeOH/CH2C2

Sources & evidence

ORD record
ord-6dd747bda9f54299941bcc2c5ae5e042
Source dataset
uspto-grants-1996_11
Patent number
US05578634

Reaction notes

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