Diisopropylethylamine → N-[6-[3-[4-(Diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[4,3-b]pyridazine-3-carbonyl]-2,2-dimethylglycine Ethyl Ester

HRID 397566Notes

Reaction equation

HRID 397566 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:37]2[N:38]=[C:39](Cl)[CH:40]=[CH:41][C:36]2=[N:35][N:34]=1)=[O:32])[CH3:26].C(N(C(C)C)C(C)C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH2:25]([O:27][C:28](=[O:45])[C:29]([CH3:44])([CH3:43])[NH:30][C:31]([C:33]1[N:37]2[N:38]=[C:39]([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:40]=[CH:41][C:36]2=[N:35][N:34]=1)=[O:32])[CH3:26]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 23000300N-(6-chloro[1,2,4]triazolo[4,3-b]pyridazine-3-carbonyl)-2,2-dimethylglycine ethyl ester

Product 1

HCID 23000293N-[6-[3-[4-(Diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[4,3-b]pyridazine-3-carbonyl]-2,2-dimethylglycine Ethyl EsterYield 50.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

1.25 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 1.20 g of N-(6-chloro[1,2,4]triazolo[4,3-b]pyridazine-3-carbonyl)-2,2-dimethylglycine ethyl ester were dissolved in 20 ml of N,N-dimethylformamide; 1.33 ml of N-ethyldiisopropylamine was added, followed by stirring under heating at an external temperature of 60° C. for 7.5 hours. After cooling, cold aqueous sodium bicarbonate was added; the reaction mixture was extracted with ethyl acetate, washed with saturated saline, and dried over magnesium sulfate. After concentration 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 under reduced pressure; the precipitated crystal was recrystallized from ethanol-ethyl acetate fir (1:3), collected by filtration, and dried, to yield 1.17 g of the title compound.

Workup

  1. temperatureAfter cooling
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washwashed with saturated saline
  4. dry with materialdried over magnesium sulfate
  5. concentrationAfter concentration under reduced pressure
  6. washeluted with ethyl acetate-methanol-triethylamine (50:5:1)
  7. customThe desired fraction was collected
  8. concentrationconcentrated under reduced pressure
  9. customthe precipitated crystal was recrystallized from ethanol-ethyl acetate fir (1:3)
  10. filtrationcollected by filtration
  11. customdried

Sources & evidence

ORD record
ord-3b6e70eab6a54532a4147175b77be483
Source dataset
uspto-grants-2003_08
Patent number
US06610694B1

Reaction notes

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