Ammonium Chloride → HCID 21025133, compound

HRID 1796593Notes

Reaction equation

HRID 1796593 reaction equation
C(O[C:4]([C:6]1[N:7]([NH2:17])[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]=1[CH3:11])=[O:5])C.S(O)(C1C=CC(C)=CC=1)(=O)=O.O.C1CCN2[C:33](=[N:34]CCC2)[CH2:32][CH2:31]1.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[CH2:15]([O:14][C:12]([C:9]1[C:10]([CH3:11])=[C:6]2[C:4](=[O:5])[C:32]([C:33]#[N:34])=[CH:31][NH:17][N:7]2[CH:8]=1)=[O:13])[CH3:16]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 521998p-Toluenesulfonic acid monohydrateHCID 11499674Diethyl 1-amino-3-methyl-1H-pyrrole-2,4-dicarboxylate

Product 1

HCID 21025133HCID 21025133, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1-amino-3-methyl-1H-pyrrole-2,4-dicarboxylic acid diethyl ester (1.08 g, 4.50 mmol) in toluene (15 mL) were added 1,1-diethoxypropionitrile (2.02 mL, 1.93 g, 13.5 mmol) and TsOH-H2O (171 mg, 0.90 mmol). The reaction mixture was heated at reflux for 12 h and then cooled to 25° C. DBU (0.18 mL, 0.822 g, 5.40 mmol) was added and the resulting dark brown mixture was heated at 80° C. for 1 h and then coded to room temperature. The reaction mixture was poured onto dichloromethane (50 mL) and NH4Cl (sat. aq., 50 mL) and the layers were separated. The aqueous layer was extracted with dichloromethane (2×30 mL) and the combined organic extracts were washed with water (30 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (10-30% methanol/dichloromethane) to provided 441 mg (40%) of compound 1C as a brown solid. HPLC: 100% at 3.383 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 246.09 [M+H]+. D Preparation of 4-Chloro-3-cyano-5-methylpyrrolo[1,2-b]pyridazine-6-carboxylic acid ethyl ester (1D)

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 12 h
  3. temperaturethe resulting dark brown mixture was heated at 80° C. for 1 h
  4. customcoded to room temperature
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with dichloromethane (2×30 mL)
  7. washthe combined organic extracts were washed with water (30 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica gel column chromatography (10-30% methanol/dichloromethane)

Sources & evidence

ORD record
ord-5b195207fc0046a0919326f329ce191e
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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