Triethylamine → 6-Chloro-N-(2-cyclopropylethyl)pyridazine-3-carboxamide

HRID 1714859Notes

Reaction equation

HRID 1714859 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([C:8]([OH:10])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH:17]1([CH2:20][CH2:21][NH2:22])[CH2:19][CH2:18]1.CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[N:7]=[N:6][C:5]([C:8]([NH:22][CH2:21][CH2:20][CH:17]2[CH2:19][CH2:18]2)=[O:10])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 64157626-chloropyridazine-3-carboxylic AcidHCID 10240761Cyclopropaneethanamine

Product 1

HCID 655615656-Chloro-N-(2-cyclopropylethyl)pyridazine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent4×

Procedure

To a suspension of 6-chloropyridazine-3-carboxylic acid (4.1 g, 25.8 mmol) from Step 1 and DMF (50 μL) in CH2Cl2 (60 mL) at r.t. was added oxalyl chloride (5.0 mL, 57.1 mmol) and the mixture was refluxed for 30 min. Volatile materials were removed in vacuo to give the crude acid chloride as a pale yellow solid. The acid chloride was dissolved in CH2Cl2 (40 mL) and added to a solution of cyclopropylethylamine (2.4 g, 28.2 mmol) and Et3N (11 mL, 78 mmol) in CH2Cl2 at 0° C. over a period of about 15 min. After further stirring for 30 min, the mixture was diluted with more CH2Cl2, washed successively with 10% HCl, saturated aqueous NaHCO3, water, dried (Na2SO4) and concentrated. Chromatography over silica gel and elution with hexanes-EtOAc (2:1) gave the title compound as a white powder. 1H NMR (500 MHz, Acetone-d6): δ 0.12 (d, 2H), 0.47 (t, 2H), 0.80 (s, 1H), 1.57-1.61 (m, 2H), 3.58-3.62 (m, 2H), 8.02 (d, 1H), 8.31 (d, 1H), 8.62 (s, 1H).

Workup

  1. temperaturethe mixture was refluxed for 30 min
  2. customVolatile materials were removed in vacuo
  3. customto give the crude acid chloride as a pale yellow solid
  4. washwashed successively with 10% HCl, saturated aqueous NaHCO3, water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. washChromatography over silica gel and elution with hexanes-EtOAc (2:1)

Sources & evidence

ORD record
ord-01cb756318994c59905983a5ba6ba2c7
Source dataset
uspto-grants-2010_09
Patent number
US07799787B2

Reaction notes

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