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

HRID 1715301Notes

Reaction equation

HRID 1715301 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.Cl.[NH2:26][CH2:27][CH2:28][CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].[CH2:37]([N:39](CC)CC)C>CN(C=O)C>[C:37]([CH2:16][C:13]1[S:14][CH:15]=[C:11]([C:7]2[S:6][C:5]([NH:4][C:1]([NH:26][CH2:27][CH2:28][CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:3])=[N:9][C:8]=2[CH3:10])[N:12]=1)#[N:39]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 119895252'-(Acetylamino)-4'-methyl-N-(tetrahydrofuran-2-ylmethyl)-4,5'-bi-1,3-thiazole-2-carboxamide2×HCID 24750478Tert-butyl 4-aminobutanoate hydrochloride

Product 1

HCID 11988517Tert-butyl 4-[({[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]amino}carbonyl)amino]butanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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). Tert-butyl 4-aminobutanoate hydrochloride (94.8 mg; 0.48 mmol; 1 eq) and triethylamine (148 μl; 1.07 mmol; 2.20 eq) are added. After less than 1 min, the mixture becomes homogeneous. After 30 min the reaction is complete. DMF is removed under reduced pressure. The resulting crude oil is dissolved in DCM and washed twice with NH4Cl sat. solution and twice with NaHCO3 sat. solution. The organic layer is dried over Na2SO4, filtered and concentrated. The resulting crude product is purified by preparative HPLC. The purified fractions are neutralized with NaHCO3 sat. solution and the desired compound is extracted with DCM.

Workup

  1. waitAfter less than 1 min
  2. customDMF is removed under reduced pressure
  3. dissolutionThe resulting crude oil is dissolved in DCM
  4. washwashed twice with NH4Cl sat. solution and twice with NaHCO3 sat. solution
  5. dry with materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude product is purified by preparative HPLC
  9. extractionthe desired compound is extracted with DCM

Sources & evidence

ORD record
ord-fc98975c7d1d488ca22fb17f625dc189
Source dataset
uspto-grants-2010_09
Patent number
US07799814B2

Reaction notes

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