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

HRID 2199161Notes

Reaction equation

HRID 2199161 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([S:9][C:10]2[CH:11]=[C:12]([CH:17]([CH3:19])[CH3:18])[C:13](=[O:16])[NH:14][N:15]=2)=[C:4]([Cl:20])[CH:3]=1.N([O-])=O.[Na+].[C:25]([CH2:27][C:28]([NH:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:29])#[N:26].[N:36]1C=CC=CC=1>O.Cl>[CH2:34]([O:33][C:31](=[O:32])[NH:30][C:28](=[O:29])[C:27]([C:25]#[N:26])=[N:36][NH:1][C:2]1[CH:3]=[C:4]([Cl:20])[C:5]([S:9][C:10]2[CH:11]=[C:12]([CH:17]([CH3:18])[CH3:19])[C:13](=[O:16])[NH:14][N:15]=2)=[C:6]([Cl:8])[CH:7]=1)[CH3:35]

Participants

7

Reactant 4

HCID 1049PyridineHCID 23112N-CyanoacetylethylcarbamateHCID 23668193Sodium NitriteHCID 598345166-(4-Amino-2,6-dichloro-phenylsulfanyl)-4-isopropyl-2H-pyridazin-3-one

Product 1

HCID 86610368(2-Cyano-2-{[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-hydrazono}-acetyl)-carbamic acid ethyl esterYield 58%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent4×

Conditions

Temperature
0 °C

Procedure

A mixture of 6-(4-amino-2,6-dichloro-phenylsulfanyl)-4-isopropyl-2H-pyridazin-3-one (85) (3.40 g, 10.4 mmol) in water (135 mL) and concentrated hydrochloric acid (68 mL) cooled to 0° C. was treated with a solution of sodium nitrite (853 mg, 12.36 mmol) in water (7.0 mL) via Pasteur pipette under the surface of the reaction mixture. This was followed by a water rinse (1.0 mL) of the Pasteur pipette. The resulting yellow mixture was stirred at 0° C. for 30 min. More concentrated hydrochloric acid (7.0 mL) was added. The reaction was stirred at 0° C. for an additional 1.3 h. The solids were removed by filtration through filter paper and were rinsed with water. The clear, yellow diazonium salt solution of the filtrate was quickly poured into a solution of cyanoacetylurethane (1.77 g, 11.33 mmol), pyridine (75 mL) and water (204 mL) cooled to 0° C. Upon mixing, orange-red solids immediately formed. This mixture was stirred at 0° C. for 1 h. At this time, the solids were collected by filtration through filter paper. The solids were washed with water, air-dried under house vacuum for 2 h, and then dried under vacuum to afford (2-cyano-2-{[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]hydrazono}-acetyl)-carbamic acid ethyl ester (86) (2.98 g, 58%) as an orange solid; ES(+)-HRMS m/e calcd for C19H18Cl2N6O4S (M+H)+ 497.0560, found 497.0559. Exact Mass=496.0487; Molecular weight=497.36

Workup

  1. washrinse (1.0 mL) of the Pasteur pipette
  2. additionMore concentrated hydrochloric acid (7.0 mL) was added
  3. stirringThe reaction was stirred at 0° C. for an additional 1.3 h
  4. customThe solids were removed by filtration
  5. filtrationthrough filter paper
  6. washwere rinsed with water
  7. temperaturecooled to 0° C
  8. additionUpon mixing
  9. customorange-red solids immediately formed
  10. stirringThis mixture was stirred at 0° C. for 1 h
  11. filtrationAt this time, the solids were collected by filtration
  12. filtrationthrough filter paper
  13. washThe solids were washed with water
  14. customair-dried under house vacuum for 2 h
  15. customdried under vacuum

Sources & evidence

ORD record
ord-4a642449c941423e9b96d9b695c4b05b
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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