Triethylamine → N-{3-[1-[4-(2-pyridyl)piperazinyl]-methyl]-[1,2,4]thiadiazol-5-yl}-L-leucyl-L-proline methyl ester

HRID 1275604Notes

Reaction equation

HRID 1275604 reaction equation
[CH3:1][O:2][C:3](=[O:24])[C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9](=[O:23])[C@H:10]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH:11][C:12]1[S:16][N:15]=[C:14]([CH2:17]Cl)[N:13]=1.[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C(N(CC)CC)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:24])[C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9](=[O:23])[C@H:10]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH:11][C:12]1[S:16][N:15]=[C:14]([CH2:17][N:34]2[CH2:35][CH2:36][N:31]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=3)[CH2:32][CH2:33]2)[N:13]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 944591-(2-Pyridyl)piperazineHCID 12052380N-(3-chloromethyl-[1,2,4]thiadiazol-5-yl)-L-leucyl-L-proline methyl ester

Product 1

HCID 12052381N-{3-[1-[4-(2-pyridyl)piperazinyl]-methyl]-[1,2,4]thiadiazol-5-yl}-L-leucyl-L-proline methyl esterYield 91.7%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-(3-chloromethyl-[1,2,4]thiadiazol-5-yl)-L-leucyl-L-proline methyl ester (0.45 g, 1.2 mmol), 1-(2-pyridyl)piperazine (0.62 mL, 4 mmol), triethylamine (1.2 mL, 8 mmol) and tetra-butylammonium bromide (100 mg) in DMF (20 mL) was stirred at room temperature for 24 h. The reaction mixture was diluted with water and ethyl acetate. The organic layer was collected, washed with water, dried (sodium sulfate), filtered and concentrated in vacuo to give a light yellow oil. Purification by column chromatography on silica gel using a solvent mixture of 5% methanol in dichloromethane afforded N-{3-[1-[4-(2-pyridyl)piperazinyl]-methyl]-[1,2,4]thiadiazol-5-yl}-L-leucyl-L-proline methyl ester as a white foam (0.55 g, 91.7 %). 1H-NMR (CDCl3) δ8.19 (m, 1H), 7.48-7.52 (m, 1H), 7.14 (br. m, 1H, NH), 6.64-6.67 (m, 2H), 4.67 (m, 1H, CHCO), 4.57 (dd, J=8.4 and 4.6 Hz, 1H, CHCO2), 3.92 (m, 1H, NCHpro), 3.62-3.78 (m, 1OH, OMe, NCHpro, N=CCH2, 2NCH2), 2.83 (m, 4H, 2NCH2), 1.62-2.30 (m, 6H, 2CH2 pro and CH2), 0.90-1.03 (2d, J=6.5 and 6.6 Hz, 7H, 2Me and 1CH); MS (m/z) 502 (M+ +1), 459, 408, 382, 300, 253, 225, 176, 147, 121, 95.

Workup

  1. customThe organic layer was collected
  2. washwashed with water
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a light yellow oil
  7. customPurification by column chromatography on silica gel using
  8. additiona solvent mixture of 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-9d8e2649a6fb44d79fd5e32a245738d7
Source dataset
uspto-grants-2000_12
Patent number
US06162791

Reaction notes

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