Acetic Acid → 920509-35-9

HRID 2199119Notes

Reaction equation

HRID 2199119 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:20]2[C:25](=[O:26])[NH:24][C:23](=[O:27])C(C#N)=[N:21]2)[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[NH:11][N:10]=1.Cl.[OH-].[Na+].[C:33]([OH:36])(=[O:35])[CH3:34]>O>[Cl:19][C:6]1[CH:5]=[C:4]([N:20]2[C:25](=[O:26])[NH:24][C:23](=[O:27])[C:34]([C:33]([OH:36])=[O:35])=[N:21]2)[CH:3]=[C:2]([Cl:1])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[NH:11][N:10]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 159812372-{3,5-Dichloro-4-[(5-isopropyl-6-oxo-1,6-dihydro-3-pyridazinyl)oxy]phenyl}-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile

Product 1

HCID 59834482920509-35-9Yield 78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (31) (136 mg, 0.312 mmol) in glacial acetic acid (3.0 mL) was treated with concentrated hydrochloric acid (0.345 mL). The reaction mixture was heated to 120° C. for 24 h. Starting material was still present by LC/MS. Additional concentrated hydrochloric acid (0.34 mL) was added. The reaction mixture was heated to 120° C. for another 24 h. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). At this time, the reaction was made basic by the addition of a 1N aqueous sodium hydroxide solution and was extracted with ether (100 mL). The organic layer was discarded. The aqueous layer was acidified by the addition of a 1N aqueous hydrochloric acid solution and was extracted with ethyl acetate (2×100 mL). The organic layers were combined, washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated under vacuum to afford 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid (32) (111 mg, 78%) as an orange solid which was used without further purification; LRMS for C17H13Cl2N5O6 (M m/z=454. Molecular Weight=454.2291; Exact Mass=453.0243

Workup

  1. temperatureThe reaction mixture was heated to 120° C. for another 24 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionwas extracted with ether (100 mL)
  4. additionThe aqueous layer was acidified by the addition of a 1N aqueous hydrochloric acid solution
  5. extractionwas extracted with ethyl acetate (2×100 mL)
  6. washwashed with a saturated aqueous sodium chloride solution
  7. dry with materialdried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-acd64ba8fbca47659397cb0a99f2264d
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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