Cesium carbonate → 6-Chloro-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid ethyl ester

HRID 1396337Notes

Reaction equation

HRID 1396337 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].[N:14]1([C:19]2[N:24]=[C:23]([NH2:25])[CH:22]=[CH:21][CH:20]=2)[CH:18]=[CH:17][N:16]=[N:15]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(=O)(O)[O-].[Na+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[N:8][C:9]([Cl:13])=[CH:10][C:11]=1[NH:25][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]([N:14]2[CH:18]=[CH:17][N:16]=[N:15]2)[N:24]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 53428795Ethyl 4,6-dichloropyridazine-3-carboxylateHCID 846512016-[1,2,3]Triazol-1-yl-pyridin-2-ylamine

Product 1

HCID 866897086-Chloro-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid ethyl esterYield 15.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

4,6-Dichloro-pyridazine-3-carboxylic acid ethyl ester (200 mg, 0.905 mmol) and 6-[1,2,3]triazol-1-yl-pyridin-2-ylamine (147 mg, 0.914 mmol) were dissolved in 1,4-dioxane (6 mL) and the solution was purged with argon. Tris(dibenzylideneacetone)dipalladium (83 mg, 0.09 mmol), Xantphos (105 mg, 0.18 mmol), and cesium carbonate (884 mg, 2.7 mmol) were added and the reaction mixture was heated to 100° C. for 1 h. The reaction mixture was cooled, diluted with saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. Purification by chromatography (silica, 25 to 100% ethyl acetate in hexanes) gave 6-chloro-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid ethyl ester (48 mg, 15%) as a light yellow solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 9.34-9.43 (m, 1H) 8.54-8.57 (m, 1H) 8.43 (d, J=1.1 Hz, 1H) 7.87-7.97 (m, 3H) 7.60 (dd, J=7.4, 1.3 Hz, 1H) 4.55 (q, J=7.2 Hz, 2H) 1.50 (t, J=7.2 Hz, 3H); MS (EI/CI) m/z: 346 [M+H].

Workup

  1. customthe solution was purged with argon
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by chromatography (silica, 25 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-290b4c712aa5453d864aad1405d213cb
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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