Sodium hydride → HCID 68804695, compound

HRID 2250649Notes

Reaction equation

HRID 2250649 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:10]2[C:11]3[N:12]([C:27]([CH2:30][CH3:31])=[CH:28][CH:29]=3)[N:13]=[C:14]([CH2:25][OH:26])[C:15]=2[CH2:16][CH2:17][CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:7]=[N:8][CH:9]=1.[N:32]1([C:38](Cl)=[O:39])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>CN(C=O)C>[N:32]1([C:38]([O:26][CH2:25][C:14]2[C:15]([CH2:16][CH2:17][CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:10]([C:6]3[CH:7]=[N:8][CH:9]=[C:4]([Br:3])[CH:5]=3)[C:11]3[N:12]([C:27]([CH2:30][CH3:31])=[CH:28][CH:29]=3)[N:13]=2)=[O:39])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 848104-Morpholinecarbonyl chlorideHCID 68802719HCID 68802719, compound

Product 1

HCID 68804695HCID 68804695, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 60% NaH (695 mg) in DMF (3 mL) was added ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[1,2-b]pyridazin-3-yl]pentanoate 5 (200 mg) under ice-water cooling and the mixture was stirred at 0° C. for 0.5 hour. To this was added 4-morpholinecarbonyl chloride (659 mg) and the mixture was stirred at ambient temperature for 15 hours. The mixture was partitioned between AcOEt and water. The organic layer was separated, washed with water and brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and AcOEt (20:1-1:1) to give [4-(5-bromo-3-pyridinyl)-3-(5-ethoxy-5-oxopentyl)-7-ethylpyrrolo[1,2-b]pyridazin-2-yl]methyl 4-morpholinecarboxylate as yellow oil (75 mg).

Workup

  1. stirringthe mixture was stirred at ambient temperature for 15 hours
  2. customThe mixture was partitioned between AcOEt and water
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with a mixture of hexane and AcOEt (20:1-1:1)

Sources & evidence

ORD record
ord-830e8a90d5524af99c6334df8fa627c9
Source dataset
uspto-grants-2008_01
Patent number
US07317009B2

Reaction notes

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