Ethyl 4,6-dichloropyridazine-3-carboxylate → 6-chloro-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazine-3-carboxylic acid ethyl ester

HRID 1396366Notes

Reaction equation

HRID 1396366 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[N:8][C:9]([Cl:13])=[CH:10][C:11]=1Cl)=[O:5])[CH3:2].[CH3:14][N:15]1[C:19]2=[N:20][C:21]([NH2:24])=[CH:22][CH:23]=[C:18]2[CH:17]=[CH:16]1>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[N:8][C:9]([Cl:13])=[CH:10][C:11]=1[NH:24][C:21]1[N:20]=[C:19]2[N:15]([CH3:14])[CH:16]=[CH:17][C:18]2=[CH:23][CH:22]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 53428795Ethyl 4,6-dichloropyridazine-3-carboxylateHCID 866897281-methyl-1H-pyrrolo[2,3-b]pyridin-6-amine

Product 1

HCID 866897296-chloro-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazine-3-carboxylic acid ethyl esterYield 18%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

4,6-Dichloro-pyridazine-3-carboxylic acid ethyl ester (195 mg, 0.882 mmol) and 1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamine (156 mg, 1.06 mmol) were dissolved in acetonitrile (2.7 mL), then heated at 140° C. for 2 d. The reaction mixture was cooled and concentrated in vacuo. The residue was diluted with water and then extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. Purification by chromatography (silica, 5 to 70% ethyl acetate in hexanes) gave 6-chloro-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazine-3-carboxylic acid ethyl ester (52 mg, 18%) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.78 (s, 1H) 9.34 (s, 1H) 7.90 (d, J=8.3 Hz, 1H) 7.14 (d, J=3.3 Hz, 1H) 6.74 (d, J=8.3 Hz, 1H) 6.45 (d, J=3.5 Hz, 1H) 4.58 (d, J=7.1 Hz, 2H) 3.90 (s, 3H) 1.52 (t, J=7.2 Hz, 3H); LCMS (EI/CI) m/z: 332 [M+H].

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by chromatography (silica, 5 to 70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0c2769bca5b5470a9efa63a367a212b4
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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