Diisopropylcarbodiimide → 3-[4-(2-chloro-phenoxy)-piperidin-1-yl]-3-oxo-N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-propionamide

HRID 1093698Notes

Reaction equation

HRID 1093698 reaction equation
[C:1]1([C:7]2[N:11]=[C:10]([NH:12][C:13](=[O:18])[CH2:14][C:15]([OH:17])=O)[S:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[Cl:20][C:21]1[CH:33]=[CH:32][CH:31]=[CH:30][C:22]=1[O:23][CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.CC(C)N=C=NC(C)C>C1COCC1>[Cl:20][C:21]1[CH:33]=[CH:32][CH:31]=[CH:30][C:22]=1[O:23][CH:24]1[CH2:29][CH2:28][N:27]([C:15](=[O:17])[CH2:14][C:13]([NH:12][C:10]2[S:9][N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:11]=2)=[O:18])[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 167325894-(2-Chlorophenoxy)piperidine hydrochlorideHCID 57874387N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acid

Product 1

HCID 578744833-[4-(2-chloro-phenoxy)-piperidin-1-yl]-3-oxo-N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-propionamideYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acid (0.07 g, 0.00027 mole) in THF (3 mL) was added, 4-(2-chloro-phenoxy)-piperidine hydrochloride (0.072 g, 0.00029 mol) followed by DIC (0.04 g, 0.00031 mole). The resulting mixture was heated to reflux for 4 hours then concentrated. The resulting residue was purified by column chromatography using neutral aluminium oxide (0.5% methanol in dichloromethane) to afford 0.045 g (37%) of 3-[4-(2-chloro-phenoxy)-piperidin-1-yl]-3-oxo-N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-propionamide. LC-MS purity: 457.1 (M+1)+, 84.85% 1H NMR (CDCl3): δ 8.2 (s, 2H), 7.5 (m, 4H), 7.2 (m, 1H), 7.0 (d, 2H), 4.7 (s, 1H), 4.2 (d, 1H), 3.8 (m, 1H), 3.6 (m, 5H), 2.0 (dd, 4H), 2.6 (bs, 3H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 4 hours
  3. concentrationthen concentrated
  4. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-be144eed95464c549382ac862b41ad4f
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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