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

HRID 1067559Notes

Reaction equation

HRID 1067559 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:44])[CH2:29][NH:30][C:31]([C:33]1[N:34]=[C:35]2[CH:40]=[CH:39][C:38](Cl)=[N:37][N:36]2[C:42]=1[Cl:43])=[O:32])[CH3:26].C(N(C(C)C)C(C)C)C>CN1CCCC1=O>[CH2:25]([O:27][C:28](=[O:44])[CH2:29][NH:30][C:31]([C:33]1[N:34]=[C:35]2[CH:40]=[CH:39][C:38]([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)=[N:37][N:36]2[C:42]=1[Cl:43])=[O:32])[CH3:26]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 22989337N-(3,6-dichloroimidazo[1,2-b]pyridazine-2-carbonyl)glycine ethyl ester

Product 1

HCID 22989271N-[3-chloro-6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazine-2-carbonyl]glycine ethyl esterYield 70.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
95 °C

Procedure

0.649 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 0.53 g of N-(3,6-dichloroimidazo[1,2-b]pyridazine-2-carbonyl)glycine ethyl ester were dissolved in 7 ml of 1-methyl-2-pyrrolidone; 0.345 ml of N-ethyldiisopropylamine was added, followed by stirring in an oil bath (90-100° C.) for 24 hours. After cooling, ice water was added, followed by extraction with ethyl acetate; the extract was washed with saline and 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 (185:15:2). The desired fraction was collected and recrystallized from ethyl acetate to yield 0.711 g of the title compound.

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washthe extract was washed with saline
  4. dry with materialdried with magnesium sulfate
  5. concentrationThe dry product was concentrated under reduced pressure
  6. washeluted with ethyl acetate:methanol:triethylamine (185:15:2)
  7. customThe desired fraction was collected
  8. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-dc8e5443991d407db4fe5b4a458c798b
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

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