1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-cyclopropyl-1-(4-{[(2-piperidin-1-ylethyl)amino]carbonyl}phenyl)-5-propyl-1H-1,2,3-triazole-4-carboxamide

HRID 1717274Notes

Reaction equation

HRID 1717274 reaction equation
[N:1]1([CH2:7][CH2:8][NH:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([N:18]3[C:22]([CH2:23][CH2:24][CH3:25])=[C:21]([C:26]([OH:28])=O)[N:20]=[N:19]3)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=C[C:32]2N(O)N=[N:35][C:33]=2[CH:34]=1.C1(N)CC1.CCN=C=NCCCN(C)C>C(#N)C.CN(C=O)C>[CH:33]1([NH:35][C:26]([C:21]2[N:20]=[N:19][N:18]([C:15]3[CH:14]=[CH:13][C:12]([C:10]([NH:9][CH2:8][CH2:7][N:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[O:11])=[CH:17][CH:16]=3)[C:22]=2[CH2:23][CH2:24][CH3:25])=[O:28])[CH2:34][CH2:32]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 68513562HCID 68513562, compound

Product 1

HCID 68513516N-cyclopropyl-1-(4-{[(2-piperidin-1-ylethyl)amino]carbonyl}phenyl)-5-propyl-1H-1,2,3-triazole-4-carboxamideYield 126.6%

Reagents, catalysts & solvents 1

HCID 21891449acetonitrile N,N-dimethylformamideSolvent

Procedure

1-(4-{[(2-Piperidin-1-ylethyl)amino]carbonyl}phenyl)-5-propyl-1H-1,2,3-triazole-4-carboxylic acid (650 mg, 1.52 mmol) obtained in Example 62b), HOBt (104 mg, 0.759 mmol, 0.5 eq.) and cyclopropylamine (0.152 ml, 2.12 mmol, 1.4 eq.) were dissolved in acetonitrile-DMF (1:1, 10 ml), WSC (386 mg, 1.97 mmol, 1.3 eq.) was added, and the mixture was stirred at room temperature for 61 hr. The reaction mixture was concentrated, dissolved in ethyl acetate (35 ml) and washed sequentially with 2% aqueous sodium carbonate solution-saturated brine (1:1, 40 ml×2, 1:4, 40 ml×1). The aqueous layers were each extracted with ethyl acetate (30 ml). The organic layers were combined and dried over anhydrous sodium sulfate and concentrated, the residue was dissolved in toluene, and the solution was subjected to column chromatography on NH silica gel (Fuji Silysia Chemical Ltd., 100-200 mesh, DM1020, 6 g). The flow-through solution and the fraction obtained by elution with ethyl acetate-hexane (1:1-2:1) were concentrated, and ethyl acetate and diethyl ether were added. The precipitate was collected by filtration, washed with diethyl ether and dried to give the title compound as a white powder (408 mg, 0.961 mmol, 63.2%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in ethyl acetate (35 ml)
  3. washwashed sequentially with 2% aqueous sodium carbonate solution-saturated brine (1:1, 40 ml×2, 1:4, 40 ml×1)
  4. extractioneach extracted with ethyl acetate (30 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. dissolutionthe residue was dissolved in toluene
  8. customThe flow-through solution and the fraction obtained by elution with ethyl acetate-hexane (1:1-2:1)
  9. concentrationwere concentrated
  10. additionethyl acetate and diethyl ether were added
  11. filtrationThe precipitate was collected by filtration
  12. washwashed with diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-d20c9a457db74173a1c5040b5e9bda11
Source dataset
uspto-grants-2010_09
Patent number
US07803822B2

Reaction notes

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