Reaction #2286350

Reaction equation

pyridine

6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-2-methyl-2H-pyridazin-3-one

6-(4-Amino-2,6-dichloro-benzyl)-4-isopropyl-2-methyl-2H-pyridazin-3-one

sodium nitrite

cyanoacetylurethane

→

(2-cyano-2-{[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-hydrazono}-acetyl)-carbamic acid ethyl ester

Yield 86.0%

(2-Cyano-2-{[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-hydrazono}-acetyl)-carbamic acid ethyl ester

Yield 86.0%

Solvents

water

water

hydrochloric acid

water

water

Conditions

Workup

1. 1
   Washrinse (0.5 mL) of the Pasteur pipette
2. 2
   FiltrationAt this time, the reaction was filtered through a pad of cotton
3. 3
   Temperaturecooled to 0° C
4. 4
   workup.ADDITIONUpon mixing
5. 5
   Otherorange-red solids immediately formed
6. 6
   workup.STIRRINGThis mixture was stirred at 0° C. for 30 min
7. 7
   FiltrationAt this time, the solids were collected by filtration
8. 8
   Filtrationthrough filter paper
9. 9
   WashThe solids were washed with water and petroleum ether
10. 10
    Otherair-dried under house vacuum
11. 11
    Otherdried under vacuum

Procedure

A mixture of 6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-2-methyl-2H-pyridazin-3-one (94) (148 mg, 0.45 mmol) in water (6 mL) and concentrated hydrochloric acid (3 mL) cooled to 0° C. was treated with a solution of sodium nitrite (37.3 mg, 0.54 mmol) in water (0.5 mL) via Pasteur pipette under the surface of the reaction mixture. This was followed by a water rinse (0.5 mL) of the Pasteur pipette. The resulting pale yellow solution was stirred at 0° C. for 45 min. At this time, the reaction was filtered through a pad of cotton and was drained directly into a solution of cyanoacetylurethane (77.3 mg, 0.49 mmol), pyridine (3 mL) and water (9 mL) cooled to 0° C. Upon mixing, orange-red solids immediately formed. This mixture was stirred at 0° C. for 30 min. At this time, the solids were collected by filtration through filter paper. The solids were washed with water and petroleum ether, air-dried under house vacuum, and then dried under vacuum to afford (2-cyano-2-{[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-hydrazono}-acetyl)-carbamic acid ethyl ester (95) (192 mg, 86%) as an orange solid; ES-HRMS m/e calcd for C21H22Cl2N6O4 (M+H)+ 493.1153, found 493.1155. Exact Mass=492.1080; Molecular weight=493.3533.

Source