Reaktion #1955153

Reaktionsgleichung

4-isobutylaminobenzenesulfonic acid 2-aminobenzo-thiazol-6-yl ester

intermediate 27

4-isobutylaminobenzenesulfonic acid 2-aminobenzo-thiazol-6-yl ester

4-carboxymethyl-piperidine-1-carboxylic acid tert-butyl ester

HBTU

N,N-diisopropylethylamine

→

4-{[6-(4-isobutylamino-benzenesulfonyloxy)benzothiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl ester

Lösungsmittel

Water

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionis extracted with ethyl acetate
2. 2
   WaschenThe organic phase is washed with water
3. 3
   Trocknenwith saturated sodium chloride solution, dried over magnesium sulfate
4. 4
   Einengenconcentrated to dryness
5. 5
   SonstigeThe residue obtained
6. 6
   Sonstigeis purified by HPLC on a Dynamax C18, 60 Å, 21×300 mm column with a 95/5 mixture of water/acetonitrile, for 5 minutes, with a gradient of from 5% to 40% in water for 5 minutes, with a gradient of from 40% to 80% of acetonitrile in water for 30 minutes, with a gradient of from 80% to 95% of acetonitrile in water for 5 minutes
7. 7
   workup.ADDITIONwith a 5/95 mixture of water/acetonitrile for 5 minutes with a flow rate of 20 ml/minute
8. 8
   SonstigeThe fractions are collected every 30 seconds
9. 9
   workup.ADDITIONThe fractions containing the expected product
10. 10
    Einengenare concentrated to dryness

Vorschrift

1st step: A solution of 4-isobutylaminobenzenesulfonic acid 2-aminobenzo-thiazol-6-yl ester (intermediate 27) (300 mg, 0.495 mmol), 4-carboxymethyl-piperidine-1-carboxylic acid tert-butyl ester (361 mg, 1.485 mmol), HBTU (563 mg, 1.485 mmol) and N,N-diisopropylethylamine (432 μl, 2.475 mmol) in 4 ml of dimethylformamide is stirred at room temperature overnight. Water is added to the reaction medium, which is extracted with ethyl acetate. The organic phase is washed with water and then with saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness. The residue obtained is purified by HPLC on a Dynamax C18, 60 Å, 21×300 mm column with a 95/5 mixture of water/acetonitrile, for 5 minutes, with a gradient of from 5% to 40% in water for 5 minutes, with a gradient of from 40% to 80% of acetonitrile in water for 30 minutes, with a gradient of from 80% to 95% of acetonitrile in water for 5 minutes, and then with a 5/95 mixture of water/acetonitrile for 5 minutes with a flow rate of 20 ml/minute. The solvents each contain 0.07% (v/v) of trifluoroacetic acid. The fractions are collected every 30 seconds and are monitored by analytical HPLC on a Hypersil C18, 4.6×50 mm column, with a gradient of from 0 to 100% of acetonitrile in water, over 10 minutes at a flow rate of 1 ml/minute. The solvents each contain 0.07% (v/v) of trifluoroacetic acid. The fractions containing the expected product are concentrated to dryness to give 4-{[6-(4-isobutylamino-benzenesulfonyloxy)benzothiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl ester.

Quelle