Potassium Carbonate → 3-[5-(2-Methoxy-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamine

HRID 2097595Notes

Reaction equation

HRID 2097595 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH:18][C:19]([N:21]2[CH2:24][CH:23]([O:25][C:26]3[CH:31]=[CH:30][C:29](Br)=[CH:28][N:27]=3)[CH2:22]2)=[O:20])[N:13]=1.C(=O)([O-])[O-:34].[K+].[K+]>C1COCC1.O.C(OCC)(=O)C>[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH2:18])[N:13]=1.[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:29]1[CH:30]=[CH:31][C:26]([O:25][CH:23]2[CH2:24][N:21]([C:19]([OH:20])=[O:34])[CH2:22]2)=[N:27][CH:28]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 667103553-(5-Bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide

Product 1

HCID 667104303-[5-(2-Methoxy-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamineYield 68%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-methoxyphenyl boronic acid in THF/H2O (10:1; 40 mL) was added to a microwave vial containing 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide (prepared as in Example 19 Step 1) 1.5 g, 4.28 mmol) and potassium carbonate (1.78 g, 12.86 mmol). Nitrogen gas was bubbled through the mixture for 5 mins then 1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.350 g, 10 mole %) was added and the vial sealed and heated at 100° C. in microwave synthesiser for 30 min. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and washed sequentially with sat. aqueous sodium carbonate solution (100 mL) then sat. sodium chloride solution (100 mL). Mixture dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo to afford a brown gum, which was purified by flash chromatography, eluting with a gradient of 80 to 100% ethyl acetate in hexane to a afford a pale yellow solid. Product was triturated with diethyl ether, filtered and dried to afford the title compound as a white solid (1.098 g, 68%)

Workup

  1. customNitrogen gas was bubbled through the mixture for 5 mins
  2. addition1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.350 g, 10 mole %) was added
  3. customthe vial sealed
  4. customThe cooled reaction mixture
  5. washwashed sequentially with sat. aqueous sodium carbonate solution (100 mL)
  6. dry with materialMixture dried over magnesium sulphate
  7. filtrationfiltered
  8. customFiltrate solvents were removed in vacuo
  9. customto afford a brown gum, which
  10. customwas purified by flash chromatography
  11. washeluting with a gradient of 80 to 100% ethyl acetate in hexane to
  12. customa afford a pale yellow solid
  13. customProduct was triturated with diethyl ether
  14. filtrationfiltered
  15. customdried

Sources & evidence

ORD record
ord-89bfe541a0d44df688d489540c39bf14
Source dataset
uspto-grants-2013_05
Patent number
US08450346B2

Reaction notes

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