Potassium ethyl malonate → ethyl [6-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazin-3-ylcarbonyl]acetate

HRID 1455953Notes

Reaction equation

HRID 1455953 reaction equation
[CH2:1]([O:8][C:9]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:10]=1[CH2:11][N:12]([C:15]1[N:20]=[N:19][C:18]([C:21]([OH:23])=O)=[CH:17][CH:16]=1)[CH2:13][CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C1NC=CN=1)(C1NC=CN=1)=O.[C:41]([O:47][CH2:48][CH3:49])(=[O:46])[CH2:42]C([O-])=O.[K+].[Cl-].[Mg+2].[Cl-]>C(#N)C.C(N(CC)CC)C>[CH2:1]([O:8][C:9]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:10]=1[CH2:11][N:12]([C:15]1[N:20]=[N:19][C:18]([C:21]([CH2:42][C:41]([O:47][CH2:48][CH3:49])=[O:46])=[O:23])=[CH:17][CH:16]=1)[CH2:13][CH3:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 3446434Potassium ethyl malonateHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 5360315Magnesium ChlorideHCID 98461706-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazine-3-carboxylic acid

Product 1

HCID 53869694ethyl [6-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazin-3-ylcarbonyl]acetateYield 86.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
5 °C

Procedure

A mixture of 6-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazine-3-carboxylic acid (12.5 g) and carbonyl di-imidazole (6.0 g) was heated at 5° C. for 1 hour. Separately, a mixture of potassium ethyl malonate (7.0 g), triethylamine (8.0 ml) and anhydrous magnesium chloride (5.0 g) in acetonitrile (200 ml) was stirred at ambient temperature for 2 hours. The two mixtures were combined and stirred for 18 hours at ambient temperature, then at reflux for 1 hour. The solvents were evaporated, and the residue partitioned between dichloromethane and 2N HCl. The organic solution was dried (MgSO4) and evaporated. The resulting residue was purified by flash chromatography, eluting with diethyl ether, to give ethyl [6-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridazin-3-ylcarbonyl]acetate (12.5 g) as a yellow gum.

Workup

  1. stirringstirred for 18 hours at ambient temperature
  2. temperatureat reflux for 1 hour
  3. customThe solvents were evaporated
  4. customthe residue partitioned between dichloromethane and 2N HCl
  5. dry with materialThe organic solution was dried (MgSO4)
  6. customevaporated
  7. customThe resulting residue was purified by flash chromatography
  8. washeluting with diethyl ether

Sources & evidence

ORD record
ord-2ecfc51f22fb4129aadd47bcba2c8270
Source dataset
uspto-grants-1998_12
Patent number
US05843942

Reaction notes

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