Diisopropylethylamine → n-[6-[3-[4-(Diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl]-2,2-dimethylglycine ethyl ester fumarate

HRID 1169103Notes

Reaction equation

HRID 1169103 reaction equation
[C:1]1([CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH2:18])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:25]([O:27][C:28](=[O:45])[C:29]([CH3:44])([CH3:43])[NH:30][C:31]([C:33]1[N:41]=[C:40]2[N:35]([N:36]=[C:37](Cl)[CH:38]=[CH:39]2)[N:34]=1)=[O:32])[CH3:26].C(N(C(C)C)C(C)C)C.C(=O)(O)[O-].[Na+].[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64]>CN(C)C=O.C(O)C>[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64].[CH2:25]([O:27][C:28](=[O:45])[C:29]([CH3:44])([CH3:43])[NH:30][C:31]([C:33]1[N:41]=[C:40]2[N:35]([N:36]=[C:37]([NH:18][CH2:17][CH2:16][CH2:15][N:12]3[CH2:13][CH2:14][CH:9]([O:8][CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:10][CH2:11]3)[CH:38]=[CH:39]2)[N:34]=1)=[O:32])[CH3:26]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 444972Fumaric AcidHCID 516892Sodium BicarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 22989275N-(6-chloro[1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl)-2,2-dimethylglycine ethyl ester

Product 1

HCID 69842953n-[6-[3-[4-(Diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl]-2,2-dimethylglycine ethyl ester fumarateYield 88.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

1.56 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 1.50 g of N-(6-chloro[1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl)-2,2-dimethylglycine ethyl ester were dissolved in 20 ml of N,N-dimethylformamide; 1.65 ml of N-ethyldiisopropylamine was added, followed by stirring at 70° C. for 16 hours. After cooling, aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate; the extract was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol:triethylamine (50:5:1). The desired fraction was collected and concentrated; 880 mg of the oily substance obtained was dissolved in 5 ml of ethanol, followed by the addition of 170 mg of fumaric acid and concentration; the resulting concentrate was powdered by the addition of ethyl ether, washed with ethyl ether, collected by filtration and dried to yield 931 mg of the title compound.

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washthe extract was washed with saturated saline
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washeluted with ethyl acetate:methanol:triethylamine (50:5:1)
  7. customThe desired fraction was collected
  8. concentrationconcentrated
  9. custom880 mg of the oily substance obtained
  10. concentrationthe resulting concentrate
  11. additionwas powdered by the addition of ethyl ether
  12. washwashed with ethyl ether
  13. filtrationcollected by filtration
  14. customdried

Sources & evidence

ORD record
ord-aca898cede1443fbb712aefd5aa7e24f
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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