Sodium Acetate → 2-[3,5-Dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile

HRID 2199169Notes

Reaction equation

HRID 2199169 reaction equation
C([O:3][C:4](=O)[NH:5][C:6](=[O:32])[C:7]([C:30]#[N:31])=[N:8][NH:9][C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([CH2:17][C:18]2[CH:23]=[C:22]([CH:24]([CH3:26])[CH3:25])[C:21](=[O:27])[N:20]([CH3:28])[N:19]=2)=[C:12]([Cl:29])[CH:11]=1)C.C([O-])(=O)C.[Na+]>C(O)(=O)C>[Cl:29][C:12]1[CH:11]=[C:10]([N:9]2[C:4](=[O:3])[NH:5][C:6](=[O:32])[C:7]([C:30]#[N:31])=[N:8]2)[CH:15]=[C:14]([Cl:16])[C:13]=1[CH2:17][C:18]1[CH:23]=[C:22]([CH:24]([CH3:26])[CH3:25])[C:21](=[O:27])[N:20]([CH3:28])[N:19]=1

Participants

4

Reactant 2

HCID 517045Sodium AcetateHCID 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 ester

Product 1

HCID 159812792-[3,5-Dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrileYield 51.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

A solution of (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) (190 mg, 0.38 mmol) in glacial acetic acid (4 mL) was treated with sodium acetate (158 mg, 1.15 mmol). The resulting mixture was heated to 120° C. for 3.5 h. The reaction was cooled to 25° C. and was then poured onto water (125 mL). The resulting orange mixture was extracted with ethyl acetate (150 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, treated with Norite neutral decolorizing carbon, filtered through celite and washed with ethyl acetate. The filtrate was concentrated under vacuum. Purification by HPLC (10-90 acetonitrile/water with 0.1% trifluoroacetic acid over 30 min) afforded 2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (96) (87.2 mg, 44%) as an off-white solid; ES-HRMS m/e calcd for C19H16Cl2N6O3 (M+H)+ 447.0734, found 447.0735. Exact Mass=446.0661; Molecular Weight=447.2838.

Workup

  1. temperatureThe reaction was cooled to 25° C.
  2. additionwas then poured onto water (125 mL)
  3. extractionThe resulting orange mixture was extracted with ethyl acetate (150 mL)
  4. washThe combined organics were washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried with magnesium sulfate
  6. additiontreated with Norite neutral decolorizing carbon
  7. filtrationfiltered through celite
  8. washwashed with ethyl acetate
  9. concentrationThe filtrate was concentrated under vacuum
  10. customPurification by HPLC (10-90 acetonitrile/water with 0.1% trifluoroacetic acid over 30 min)

Sources & evidence

ORD record
ord-5e9bb09744574bc98f14f2f999ead3ef
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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