Diisopropylethylamine → N-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl]glycine ethyl ester

HRID 1067568Notes

Reaction equation

HRID 1067568 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:43])[CH2:29][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+]>CN(C)C=O>[CH2:25]([O:27][C:28](=[O:43])[CH2:29][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

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 22989303N-(6-chloro[1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl)glycine ethyl ester

Product 1

HCID 22989377N-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl]glycine ethyl esterYield 39.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.41 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 1.23 g of N-(6-chloro[1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl)glycine ethyl ester were dissolved in 17 ml of N,N-dimethylformamide; 1.50 ml of N-ethyldiisopropylamine was added, followed by stirring at room temperature for 28 hours, then at 60° C. for 19 hours. After cooling, aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate-tetrahydrofuran (1:1); the extract was dried with magnesium sulfate. The dry product was 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, concentrated, recrystallized by the addition of tetrahydrofuran, collected by filtration, washed with ethyl ether and dried to yield 987 mg of the title compound.

Workup

  1. waitat 60° C. for 19 hours
  2. temperatureAfter cooling
  3. extractionfollowed by extraction with ethyl acetate-tetrahydrofuran (1:1)
  4. dry with materialthe extract was dried with magnesium sulfate
  5. concentrationThe dry product was concentrated under reduced pressure
  6. washeluted with ethyl acetate:methanol:triethylamine (50:5:1)
  7. customThe desired fraction was collected
  8. concentrationconcentrated
  9. customrecrystallized by the addition of tetrahydrofuran
  10. filtrationcollected by filtration
  11. washwashed with ethyl ether
  12. customdried

Sources & evidence

ORD record
ord-572f488a777c4b89857a670ffb9f69ba
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

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