Sodium hydride → HCID 66875104, compound

HRID 2381488Notes

Reaction equation

HRID 2381488 reaction equation
[CH3:1][N:2]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:3]1[CH:8]=[N:7][NH:6][C:5](=[O:9])[CH:4]=1.[H-].[Na+].[CH3:18][O:19][C:20](=[O:29])[CH:21](Br)[CH2:22][CH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>O1CCCC1>[CH3:18][O:19][C:20](=[O:29])[CH:21]([N:6]1[C:5](=[O:9])[CH:4]=[C:3]([N:2]([CH3:1])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=[N:7]1)[CH2:22][CH:23]1[CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×HCID 66875499HCID 66875499, compound

Product 1

HCID 66875104HCID 66875104, compoundYield 52.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 5-(methyl-phenyl-amino)-2H-pyridazin-3-one (74.3 mg, 0.36 mmol) in tetrahydrofuran (1.8 mL) cooled to 0° C. was treated with a 60% suspension of sodium hydride in mineral oil (19.7 mg, 0.49 mmol). Upon complete addition of the sodium hydride, the cooling bath was removed and additional tetrahydrofuran (1.8 mL) was added to facilitate stirring. The reaction was stirred at 25° C. for 2.25 h. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 0.11 g, 0.46 mmol). The reaction was then warmed to 50° C., where it stirred overnight. After this time, the reaction was cooled to 25° C. and stirred overnight. At this point, the reaction was partitioned between water (25 mL) and methylene chloride (3×25 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×25 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix 8 g, 15-35% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-[4-(methyl-phenyl-amino)-6-oxo-6H-pyridazin-1-yl]-propionic acid methyl ester (67.4 mg, 51%) as a yellow oil.

Workup

  1. customthe cooling bath was removed
  2. additionadditional tetrahydrofuran (1.8 mL) was added
  3. stirringThe reaction was stirred at 25° C. for 2.25 h
  4. stirringwhere it stirred overnight
  5. temperatureAfter this time, the reaction was cooled to 25° C.
  6. stirringstirred overnight
  7. customAt this point, the reaction was partitioned between water (25 mL) and methylene chloride (3×25 mL)
  8. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (1×25 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a9cbc94dccc84b7b91bc8196cff0f2fb
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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