Sodium hydride → US10918640, Example 14

HRID 1469363

Reaction equation

HRID 1469363 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:5]=[N:6][CH:7]=[CH:8][CH:9]=1.[N+](C1C=CC([O:19][C:20]([N:22]2[CH2:25][CH:24]([O:26][C:27]3[CH:32]=[CH:31][C:30]([I:33])=[CH:29][N:28]=3)[CH2:23]2)=O)=CC=1)([O-])=O.C(=O)(O)[O-].[Na+]>CN(C=O)C>[N:6]1[CH:7]=[CH:8][CH:9]=[C:4]([NH:3][C:20]([N:22]2[CH2:23][CH:24]([O:26][C:27]3[CH:32]=[CH:31][C:30]([I:33])=[CH:29][N:28]=3)[CH2:25]2)=[O:19])[N:5]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 230373AminopyridazineHCID 516892Sodium BicarbonateHCID 580730963-(5-Iodo-pyridin-2-yloxy)-azetidine-1-carboxylic acid 4-nitro-phenyl ester

Product 1

HCID 66710496US10918640, Example 14Yield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To an ice-bath cooled solution of sodium hydride (60 wt % in mineral oil, (2.1 g, 52.4 mmol) in DMF (50 mL) under nitrogen atmosphere was added (dropwise) a solution of 3-aminopyridazine (2.74 g, 28.79 mmol) in DMF (50 mL). After several minute a solution of 3-(5-iodo-pyridin-2-yloxy)-azetidine-1-carboxylic acid 4-nitro-phenyl ester (Example 5, step 3); 11.54 g, 26.18 mmol) in DMF (40 mL) was added. After 5 min the cooling bath was removed and reaction allowed to warm to ambient temperature and stir for 1.5 hr. Saturated sodium bicarbonate solution (500 mL) was added and the mixture was extracted with EtOAc (4×400 mL). Combined organic phases were washed with sat sodium chloride solution (500 mL), dried over sodium sulphate and filtered. The filtrate solvents were removed in vacuo to afford a crude product that was triturated with diethyl ether to afford the title compound (7.52 g, 72%) as a colourless solid.

Workup

  1. customAfter 5 min the cooling bath was removed
  2. customreaction
  3. extractionthe mixture was extracted with EtOAc (4×400 mL)
  4. washCombined organic phases were washed with sat sodium chloride solution (500 mL)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customThe filtrate solvents were removed in vacuo
  8. customto afford a crude product that
  9. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-9a853fd2d6cc4f0bbd016333bac771d8
Source dataset
uspto-grants-2015_04
Patent number
US09006269B2

Linked notes

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