1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → ethyl 1-{2-[2-(tert-butoxycarbonyl)hydrazino]-2-oxoethyl}-1H-pyrazole-4-carboxylate

HRID 1257425Notes

Reaction equation

HRID 1257425 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([CH2:11][C:12]([OH:14])=O)[CH:10]=1)=[O:5])[CH3:2].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[NH2:37]>ClCCl.O>[C:41]([O:40][C:38]([NH:36][NH:37][C:12](=[O:14])[CH2:11][N:9]1[CH:10]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:7]=[N:8]1)=[O:39])([CH3:44])([CH3:43])[CH3:42]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 70091tert-Butyl carbazateHCID 757711-HydroxybenzotriazoleHCID 59557975[4-(ethoxycarbonyl)-1H-pyrazol-1-yl]acetic acid

Product 1

HCID 66939602ethyl 1-{2-[2-(tert-butoxycarbonyl)hydrazino]-2-oxoethyl}-1H-pyrazole-4-carboxylateYield 62.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of the compound (9.4 g) obtained in Example 115b, N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide (18.1 g) and 1-hydroxybenzotriazole (6.5 g) in dichloromethane (100 mL) was cooled to −20° C., and a solution of tert-butyl hydrazinecarboxylate (9.5 g) in dichloromethane (20 mL) was added dropwise. The reaction mixture was stirred at room temperature overnight, poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (carrier: silica gel, eluent: petroleum ether/ethyl acetate/triethylamine=10/1/0.001) to give ethyl 1-{2-[2-(tert-butoxycarbonyl)hydrazino]-2-oxoethyl}-1H-pyrazole-4-carboxylate (9.2 g) as a colorless solid. The solid was dissolved in ethyl acetate (50 mL), and hydrogen chloride-ethyl acetate (50 mL) was added. The mixture was stirred at room temperature for 1 hr, and the precipitate was collected by filtration to give the title compound (6.0 g) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (carrier: silica gel, eluent: petroleum ether/ethyl acetate/triethylamine=10/1/0.001)

Sources & evidence

ORD record
ord-31ba8520b6cb4f45b7399c0e8b461b51
Source dataset
uspto-grants-2013_06
Patent number
US08461348B2

Reaction notes

Loading…