Sodium hydride → HCID 68802368, compound

HRID 860502Notes

Reaction equation

HRID 860502 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:10]2[C:11]3[N:12]([C:25]([CH2:28][CH3:29])=[CH:26][CH:27]=3)[N:13]=[C:14]([CH2:23][OH:24])[C:15]=2[CH2:16][CH2:17][C:18]([O:20]CC)=[O:19])[CH:7]=[N:8][CH:9]=1.Br.Br[CH2:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1>CN(C=O)C>[Br:3][C:4]1[CH:5]=[C:6]([C:10]2[C:11]3[N:12]([C:25]([CH2:28][CH3:29])=[CH:26][CH:27]=3)[N:13]=[C:14]([CH2:23][O:24][CH2:32][C:33]3[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=3)[C:15]=2[CH2:16][CH2:17][C:18]([OH:20])=[O:19])[CH:7]=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 127070373-(Bromomethyl)pyridine hydrobromideHCID 68802937HCID 68802937, compound

Product 1

HCID 68802368HCID 68802368, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 60% NaH (74 mg) in DMF (3 mL) was added ethyl 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[1,2-b]pyridazin-3-yl]propanoate (200 mg) under ice-water cooling, and the mixture was stirred at 0° C. for 0.5 hour. To this was added 3-(bromomethyl)pyridine hydrobromide (234 mg) under ice-water cooling, and the mixture was stirred at ambient temperature for 2 hours. The mixture was partitioned between AcOEt and water. The aqueous layer was separated, acidified to pH 3–4 with HCl and extracted with AcOEt. The organic layer was 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 CHCl3 and MeOH (100:1-20:1) to give 3-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(3-pyridinylmethoxy)methyl]pyrrolo[1,2-b]pyridazin-3-yl}propanoic acid as a yellow powder (110 mg).

Workup

  1. stirringthe mixture was stirred at ambient temperature for 2 hours
  2. customThe mixture was partitioned between AcOEt and water
  3. customThe aqueous layer was separated
  4. extractionextracted with AcOEt
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over MgSO4
  7. customevaporated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with a mixture of CHCl3 and MeOH (100:1-20:1)

Sources & evidence

ORD record
ord-332a45524c18419aa28ab42f8454d1ff
Source dataset
uspto-grants-2006_12
Patent number
US07153854B2

Reaction notes

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