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

HRID 1715262Notes

Reaction equation

HRID 1715262 reaction equation
[C:1]([NH:4][C:5]1[S:6][C:7]([C:11]2[N:12]=[C:13]([C:16](OCC)=O)[S:14][CH:15]=2)=[C:8]([CH3:10])[N:9]=1)(=[O:3])[CH3:2].[CH2:21]([N:23](CC)CC)C.C(CC(N)=S)#N>CCO>[C:21]([CH2:16][C:13]1[S:14][CH:15]=[C:11]([C:7]2[S:6][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[N:9][C:8]=2[CH3:10])[N:12]=1)#[N:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 14162772-CyanoethanethioamideHCID 11989521Ethyl 2'-(acetylamino)-4'-methyl-4,5'-bi-1,3-thiazole-2-carboxylate2×

Product 1

HCID 11989522N-[2-(cyanomethyl)-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl]acetamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

N-[5-(bromoacetyl)-4-methyl-1,3-thiazol-2-yl]acetamide (Intermediate 1)(1.0 g; 2.79 mmol; 1 eq.) is dissolved in EtOH (25 ml). Triethylamine (980 μl; 6.98 mmol; 2.50 eq.) and 2-cyanothioacetamide (Aldrich)(279.7 mg; 2.79 mmol; 1 eq.) are added. The mixture is stirred 2 h30 at rt. Solvents are evaporated and the crude product is purified by flash chromatography, with cyclohexane/EtOAc gradient as eluent. Compound (3) is isolated as a white-off powder (680.3 mg; 88%). HPLC (method A), Rt 2.30 min (purity: 92.79%). Compound (3) is further crystallized in EtOAc, affording a new batch as colorless needles (412.60 mg; 52.75%). 1H NMR (DMSO-d6, 300 MHz) δ 2.13 (s, 3H), 2.47 (s, 3H), 4.61 (s, 2H), 7.71 (s, 1H), 12.12 (br s, 1H). M− (ESI): 277; M+ (ESI): 279. HPLC (method A), Rt: 2.28 min (purity: 99.5%).

Workup

  1. customSolvents are evaporated
  2. customthe crude product is purified by flash chromatography, with cyclohexane/EtOAc gradient as eluent

Sources & evidence

ORD record
ord-732d6948e6844071aafc71f4978e0cdb
Source dataset
uspto-grants-2010_09
Patent number
US07799814B2

Reaction notes

Loading…