Pyridine → (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

HRID 2199168Notes

Reaction equation

HRID 2199168 reaction equation
[NH2:1][C:2]1[CH:19]=[C:18]([Cl:20])[C:5]([CH2:6][C:7]2[CH:8]=[C:9]([CH:15]([CH3:17])[CH3:16])[C:10](=[O:14])[N:11]([CH3:13])[N:12]=2)=[C:4]([Cl:21])[CH:3]=1.N([O-])=O.[Na+].[C:26]([CH2:28][C:29]([NH:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:30])#[N:27].[N:37]1C=CC=CC=1>O.Cl>[CH2:35]([O:34][C:32](=[O:33])[NH:31][C:29](=[O:30])[C:28]([C:26]#[N:27])=[N:37][NH:1][C:2]1[CH:3]=[C:4]([Cl:21])[C:5]([CH2:6][C:7]2[CH:8]=[C:9]([CH:15]([CH3:17])[CH3:16])[C:10](=[O:14])[N:11]([CH3:13])[N:12]=2)=[C:18]([Cl:20])[CH:19]=1)[CH3:36]

Participants

7

Reactant 4

HCID 1049PyridineHCID 23112N-CyanoacetylethylcarbamateHCID 23668193Sodium NitriteHCID 598344356-(4-Amino-2,6-dichloro-benzyl)-4-isopropyl-2-methyl-2H-pyridazin-3-one

Product 1

HCID 72574095(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 esterYield 86%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent4×

Conditions

Temperature
0 °C

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.

Workup

  1. washrinse (0.5 mL) of the Pasteur pipette
  2. filtrationAt this time, the reaction was filtered through a pad of cotton
  3. temperaturecooled to 0° C
  4. additionUpon mixing
  5. customorange-red solids immediately formed
  6. stirringThis mixture was stirred at 0° C. for 30 min
  7. filtrationAt this time, the solids were collected by filtration
  8. filtrationthrough filter paper
  9. washThe solids were washed with water and petroleum ether
  10. customair-dried under house vacuum
  11. customdried under vacuum

Sources & evidence

ORD record
ord-b6e3098512c64b04ad1479d9bc856144
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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