p-Toluidine → HCID 86689713, compound

HRID 1396343Notes

Reaction equation

HRID 1396343 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[N:7][C:8]([Cl:12])=[CH:9][C:10]=1Cl)=[O:4].[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>CN(C)C(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[N:7][C:8]([Cl:12])=[CH:9][C:10]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)=[O:4]

Participants

7

Reactant 4

HCID 7813p-ToluidineHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 17848322Methyl 4,6-dichloropyridazine-3-carboxylate

Product 1

HCID 86689713HCID 86689713, compoundYield 79.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

4,6-Dichloro-pyridazine-3-carboxylic acid methyl ester (200 mg, 0.966 mmol), p-toluidine (104 mg, 0.966 mmol) and N,N-diisopropylethylamine (0.34 mL, 1.93 mmol) were dissolved in N,N-dimethylacetamide (2.4 mL), then heated at 110° C. for 1 h. The reaction mixture was cooled, then poured into ethyl acetate and water. The aqueous layer was extracted with ethyl acetate, and then the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by chromatography (silica, 0 to 50% ethyl acetate in hexanes) gave 6-chloro-4-p-tolylamino-pyridazine-3-carboxylic acid methyl ester (214 mg, 79%) as an off-white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 9.61 (br. s., 1H) 7.23-7.32 (m, 2H) 7.13 (d, J=7.9 Hz, 2H) 6.96 (s, 1H) 4.08 (s, 3H) 2.41 (s, 3H); LCMS (EI/CI) m/z: 278 [M+H].

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography (silica, 0 to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6f3539c7d1c744fdadc74fba0a948466
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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