Triethylamine → tert-butyl N-({[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]amino}carbonyl)glycinate

HRID 1715300Notes

Reaction equation

HRID 1715300 reaction equation
[C:1]([NH:4][C:5]1[S:6][C:7]([C:11]2[N:12]=[C:13]([C:16](NCC3CCCO3)=O)[S:14][CH:15]=2)=[C:8]([CH3:10])[N:9]=1)(=[O:3])C.[C:25]([O:29][C:30](=[O:33])[CH2:31][NH2:32])([CH3:28])([CH3:27])[CH3:26].[CH2:34]([N:36](CC)CC)C>CN(C=O)C>[C:34]([CH2:16][C:13]1[S:14][CH:15]=[C:11]([C:7]2[S:6][C:5]([NH:4][C:1]([NH:32][CH2:31][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:33])=[O:3])=[N:9][C:8]=2[CH3:10])[N:12]=1)#[N:36]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 151417Glycine tert-butyl esterHCID 119895252'-(Acetylamino)-4'-methyl-N-(tetrahydrofuran-2-ylmethyl)-4,5'-bi-1,3-thiazole-2-carboxamide2×

Product 1

HCID 11988393tert-butyl N-({[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]amino}carbonyl)glycinateYield 124.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]-1H-imidazole-1-carboxamide (Intermediate 6) (160 mg; 0.48 mmol; 1 eq) is dissolved in DMF (8 ml). A solution of glycine tert-butyl ester (63.5 mg; 0.48 mmol; 1 eq) in DMF (1 ml) and triethylamine (74 μl; 0.53 mmol; 1.10 eq) are added. After less than 1 min the mixture becomes homogeneous. After 45 min, the reaction is complete. DMF is removed under reduced pressure to afford 235.8 mg of a dark brown solid, which 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, affording Compound (65) as a brown solid (27.30 mg; 14%).

Workup

  1. waitAfter less than 1 min the mixture becomes homogeneous
  2. customDMF is removed under reduced pressure

Sources & evidence

ORD record
ord-c03f8be9269448b9b861f28e062079cf
Source dataset
uspto-grants-2010_09
Patent number
US07799814B2

Reaction notes

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