Acetic Acid → HCID 66742595, compound

HRID 1431064Notes

Reaction equation

HRID 1431064 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([O:17][C:18]([CH3:22])([CH3:21])[CH:19]=O)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[NH:41]1[CH2:44][CH2:43][CH2:42]1.C(=O)(O)[O-].[Na+]>ClCCl>[N:41]1([CH2:19][C:18]([CH3:21])([CH3:22])[O:17][C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:4]3[C:5](=[O:9])[N:6]([CH3:8])[N:7]=[C:2]([Cl:1])[CH:3]=3)=[N:16][CH:15]=2)[CH2:44][CH2:43][CH2:42]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 10422AzetidineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86662317HCID 86662317, compound

Product 1

HCID 66742595HCID 66742595, compoundYield 65.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

A pressure flask containing 2-[6-(6-chloro-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-ylamino)-pyridin-3-yloxy]-2-methyl-propionaldehyde (188 mg, 0.582 mmol) was taken up in dichloromethane (2.5 ml). Sodium triacetoxyborohydride (309 mg, 1.46 mmol) and acetic acid (0.1 ml, 1.75 mmol) were added and the flask was next cooled in an ice bath under nitrogen atmosphere. Azetidine (0.24 ml, 3.49 mmol) was added and the flask was sealed. The flask was placed in an oil bath heated to 50° C. and stirred for 16 hours. The mixture was cooled to ambient and taken up in dichloromethane (50 ml) and a saturated solution of aqueous sodium bicarbonate (50 ml). The material was transferred to a separatory funnel and shaken. The organic phase was collected and washed with a solution of 50% diluted brine (50 ml). The dichloromethane phase was collected and the aqueous phases were back extracted with methylene chloride (2×40 ml). The combined organic phase was dried (magnesium sulfate), filtered and concentrated in vacuo. The crude residue was loaded onto two preparatory TLC plates and eluted with 8% methanol/dichloromethane. The product band was collected to provide the desired product as a light white-brown powder (139 mg). (M+H)+=364 m/e.

Workup

  1. temperaturethe flask was next cooled in an ice bath under nitrogen atmosphere
  2. customthe flask was sealed
  3. customThe flask was placed in an oil bath
  4. temperatureThe mixture was cooled to ambient and
  5. customThe material was transferred to a separatory funnel
  6. stirringshaken
  7. customThe organic phase was collected
  8. washwashed with a solution of 50% diluted brine (50 ml)
  9. customThe dichloromethane phase was collected
  10. extractionthe aqueous phases were back extracted with methylene chloride (2×40 ml)
  11. dry with materialThe combined organic phase was dried (magnesium sulfate)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. washeluted with 8% methanol/dichloromethane
  15. customThe product band was collected

Sources & evidence

ORD record
ord-758b7307efca465fa93c95f49ad2d4b1
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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