Triethylamine → N-[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]-N'-[2-(5-isopropyl-1,2,4-oxadiazol-3-yl)ethyl]urea

HRID 1715302Notes

Reaction equation

HRID 1715302 reaction equation
[CH:1]([C:4]1[O:8][N:7]=[C:6]([CH2:9][CH2:10][NH2:11])[N:5]=1)([CH3:3])[CH3:2].[CH2:12]([N:14](CC)CC)C.[C:19]([NH:22][C:23]1[S:24][C:25]([C:29]2[N:30]=[C:31]([C:34](NCC3CCCO3)=O)[S:32][CH:33]=2)=[C:26]([CH3:28])[N:27]=1)(=[O:21])C>CN(C=O)C>[C:12]([CH2:34][C:31]1[S:32][CH:33]=[C:29]([C:25]2[S:24][C:23]([NH:22][C:19]([NH:11][CH2:10][CH2:9][C:6]3[N:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[O:8][N:7]=3)=[O:21])=[N:27][C:26]=2[CH3:28])[N:30]=1)#[N:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 119895252'-(Acetylamino)-4'-methyl-N-(tetrahydrofuran-2-ylmethyl)-4,5'-bi-1,3-thiazole-2-carboxamide2×HCID 176049972-(5-(Propan-2-yl)-1,2,4-oxadiazol-3-yl)ethan-1-amine

Product 1

HCID 11988783N-[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]-N'-[2-(5-isopropyl-1,2,4-oxadiazol-3-yl)ethyl]urea

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(5-Isopropyl-1,2,4-oxadiazol-3-yl)ethanamine (Amine 16) (129.2 mg; 0.48 mmol; 2 eq) is dissolved in DMF (4 ml). Triethylamine (133 μl; 0.96 mmol; 4 eq) and N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]-1H-imidazole-1-carboxamide (Intermediate 6) (79.3 mg; 0.24 mmol; 1 eq) are added. After less than 1 min the mixture becomes homogeneous, and after 30 min the reaction is complete. Solvents are evaporated and the resulting crude product is purified by preparative HPLC. The purified fractions are neutralized with NaHCO3 sat. solution and the desired product is extracted with DCM. The combined organic layers are dried over MgSO4, filtered and concentrated to Compound (82) as a white powder (29.6 mg; 30%).

Workup

  1. waitAfter less than 1 min the mixture becomes homogeneous
  2. customSolvents are evaporated
  3. customthe resulting crude product is purified by preparative HPLC
  4. extractionthe desired product is extracted with DCM
  5. dry with materialThe combined organic layers are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to Compound (82) as a white powder (29.6 mg; 30%)

Sources & evidence

ORD record
ord-97a1fd9d9eed4e2b9cd1e0c608ad8d60
Source dataset
uspto-grants-2010_09
Patent number
US07799814B2

Reaction notes

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