1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → GLPG-0778

HRID 2402604Notes

Reaction equation

HRID 2402604 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH:31]1([C:34]([NH:36][C:37]2[N:54]=[C:40]3[CH:41]=[CH:42][CH:43]=[C:44]([C:45]4[CH:53]=[CH:52][C:48]([C:49](O)=[O:50])=[CH:47][CH:46]=4)[N:39]3[N:38]=2)=[O:35])[CH2:33][CH2:32]1.Cl.[CH3:56][C:57]1([CH3:61])[CH2:60][NH:59][CH2:58]1>C(Cl)Cl.O>[CH3:56][C:57]1([CH3:61])[CH2:60][N:59]([C:49]([C:48]2[CH:47]=[CH:46][C:45]([C:44]3[N:39]4[N:38]=[C:37]([NH:36][C:34]([CH:31]5[CH2:33][CH2:32]5)=[O:35])[N:54]=[C:40]4[CH:41]=[CH:42][CH:43]=3)=[CH:53][CH:52]=2)=[O:50])[CH2:58]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 42597466HCID 42597466, compoundHCID 509881203,3-Dimethylazetidine--hydrogen chloride (1/1)

Product 1

HCID 44603362GLPG-0778

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

EDCI (3.59 g, 0.019 mol), HOBt (2.53 g, 0.019 mol) and DIPEA (4.48 mL) were added to a solution of 4-[2-(Cyclopropanecarbonyl-amino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-benzoic acid (4 g, 0.012 mol) in DCM (150 mL) at room temperature. The resulting mixture was stirred for 10 min at room temperature. Dimethylazetidine hydrochloride salt (1.64 g, 0.013 mol) was added to the solution and the reaction is stirred for 16 hrs. Water was added to the reaction mixture. The organic layer was separated and washed with 2 N NaOH solution, 2N HCl solution and water. The organic phase was dried over MgSO4, filtered and evaporated under vacuum. Purification by flash chromatography (eluant: 1:1 petrol/EtOAc to neat EtOAc) afforded cyclopropanecarboxylic acid{5-[4-(3,3-dimethyl-azetidine-1-carbonyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl}-amide.

Workup

  1. stirringthe reaction is stirred for 16 hrs
  2. customThe organic layer was separated
  3. washwashed with 2 N NaOH solution, 2N HCl solution and water
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated under vacuum
  7. customPurification by flash chromatography (eluant: 1:1 petrol/EtOAc to neat EtOAc)

Sources & evidence

ORD record
ord-d1befc1df4914e9d847732b350e0efbd
Source dataset
uspto-grants-2014_08
Patent number
US08796457B2

Reaction notes

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