Diethyl (ethoxymethylene)malonate → Diethyl 2-(((2-(Morpholin-4-ylmethyl)-1,3-thiazol-5-yl)amino)methylene)malonate

HRID 411210Notes

Reaction equation

HRID 411210 reaction equation
[N:1]1([CH2:7][C:8]2[S:9][C:10]([NH2:13])=[CH:11][N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(O[CH:17]=[C:18]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:19]([O:21][CH2:22][CH3:23])=[O:20])C>N1C=CC=CC=1.O>[N:1]1([CH2:7][C:8]2[S:9][C:10]([NH:13][CH:17]=[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:11][N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 6871Diethyl (ethoxymethylene)malonateHCID 223971412-(Morpholin-4-ylmethyl)-1,3-thiazol-5-amine

Product 1

HCID 22397215Diethyl 2-(((2-(Morpholin-4-ylmethyl)-1,3-thiazol-5-yl)amino)methylene)malonateYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a solution of 2-(morpholin-4-ylmethyl)-1,3-thiazol-5-amine (Preparation 27, 1.13 g) in pyridine (10 mL) at 45° C. is added diethyl ethoxymethylenemalonate (2.26 mL). The mixture is stirred overnight, diluted with water (100 mL), and extracted with EtOAc (3×75 mL). The organic layer is dried (MgSO4) and the solvent removed. The residue is purified by column chromatography (eluent 50% EtOAc/hexane) to afford 1.51 g (86%) of the title compound as a brown oil. Physical characteristics: 1H NMR (CDCl3) δ 1.27-1.37, 2.58, 3.72, 3.73, 4.20-4.30, 8.10, 11.02; IR (diffuse reflectance) 1687, 1637, 1596, 1416, 1337, 1301, 1274, 1268, 1243, 1234, 1114, 1094, 1011, 867, 801 cm−1; HRMS (FAB) m/z 370.1420 (C16H23N3O5S+H). Anal. Found: C, 51.80; H, 6.32; N, 11.26.

Workup

  1. extractionextracted with EtOAc (3×75 mL)
  2. dry with materialThe organic layer is dried (MgSO4)
  3. customthe solvent removed
  4. customThe residue is purified by column chromatography (eluent 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-8466d0b4da954502ae6632e5211f861a
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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