Chlorosuccinimide → {3-[3-(tert-butoxycarbonyl-cyclopropylmethyl-amino)-propylamino]-6-chloro-2-oxo-2H-pyrazin-1-yl}-acetic acid ethyl ester

HRID 1795297Notes

Reaction equation

HRID 1795297 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][N:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][CH2:13][CH2:14][CH2:15][N:16]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:7]1=[O:28])[CH3:2].[Cl:30]N1C(=O)CCC1=O>ClCCCl>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][N:6]1[C:11]([Cl:30])=[CH:10][N:9]=[C:8]([NH:12][CH2:13][CH2:14][CH2:15][N:16]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:17][CH:18]2[CH2:19][CH2:20]2)[C:7]1=[O:28])[CH3:2]

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 21023630{3-[3-(tert-butoxycarbonyl-cyclopropylmethyl-amino)-propylamino]-2-oxo-2H-pyrazin-1-yl}-acetic acid ethyl ester

Product 1

HCID 21023631{3-[3-(tert-butoxycarbonyl-cyclopropylmethyl-amino)-propylamino]-6-chloro-2-oxo-2H-pyrazin-1-yl}-acetic acid ethyl esterYield 90.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of {3-[3-(tert-butoxycarbonyl-cyclopropylmethyl-amino)-propylamino]-2-oxo-2H-pyrazin-1-yl}-acetic acid ethyl ester (250 mg, 0.61 mmol, preparation described in example 21, step D) and N-chlorosuccinimide (73 mg, 0.55 mmol) in 1,2-dichloroethane (4.2 ml) was heated to 80° C. for 1.5 h. Additional N-chlorosuccinimide (8 mg) was added and the reaction mixture was heated for 1 h. Concentration and flash chromatography (silica gel, hexane-ethyl acetate, 80:20) gave {3-[3-(tert-butoxycarbonyl-cyclopropylmethyl-amino)-propylamino]-6-chloro-2-oxo-2H-pyrazin-1-yl}-acetic acid ethyl ester (0.22 g, 81%); 1H NMR (CDCl3, 400 MHz) δ 6.94 (s, 1H), 4.90 (s, 2H), 4.26 (q, 2H, J=7.1 Hz), 3.40 (m, 4H), 3.10 (m, 2H), 1.87 (m, 2H), 1.48 (s, 9H), 1.31 (t, 3H, J=7.1 Hz), 0.97 (m, 1H), 0.49 (m, 2H), 0.21 (m, 2H).

Workup

  1. temperaturethe reaction mixture was heated for 1 h
  2. concentrationConcentration and flash chromatography (silica gel, hexane-ethyl acetate, 80:20)

Sources & evidence

ORD record
ord-a29644e0a77e4260bdea98b75824266a
Source dataset
uspto-grants-2006_04
Patent number
US07026324B2

Reaction notes

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