Triethylamine → HCID 9954774, compound

HRID 1107264Notes

Reaction equation

HRID 1107264 reaction equation
[C:1]1([CH:7]([C:15]2[N:19]=[C:18](Cl)[S:17][N:16]=2)[O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(N(CC)CC)C>CN(C=O)C.O.C(OCC)(=O)C>[C:1]1([CH:7]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[C:15]2[N:19]=[C:18]([N:30]3[CH2:31][CH2:32][N:27]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=4)[CH2:28][CH2:29]3)[S:17][N:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 944591-(2-Pyridyl)piperazineHCID 14763544HCID 14763544, compound

Product 1

HCID 9954774HCID 9954774, compoundYield 98.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-[1-phenyl-1-(tetrahydropyran-2-yloxy)methyl]-5-chloro-[1,2,4]thiadiazole (3.11 g, 10 mmol) in DMF (50 mL) was added 1-(2-pyridyl)piperazine (3.26 g, 20 mmol) dissolved in DMF (5 mL) followed by triethylamine (4.04 g, 40 mmol). The resulting mixture was stirred at room temperature for 30 min then diluted with water (150 mL) and ethyl acetate (150 mL). The organic layer was collected, washed with water (100 mL), dried (sodium sulfate), filtered and concentrated in vacuo. Purification by column chromatography on silica gel using a solvent gradient of a mixture of hexane and ethyl acetate (7/3 and 1/1) afforded 1 -{3-[phenyl-(tetrahydropyran-2-yloxy) methyl]-[1,2,4]thiadiazol -5-yl}4-pyridin-2-yl-piperazine (4.31 g, 98.4%) as a colorless foam and as a mixture of diastereoisomers. 1H-NMR (CDCl3) δ8.22 (d, J=4.6 Hz, 1H, Py-H), 7.51-7.58 (m, 3H), 7.27-7.39 (m, 3H), 6.68-6.71 (m, 2H), 5.93 and 5.88 (s, 0.5H each, αH), 4.91 and 4.67 (t, J=3.2 Hz, 0.5H each, OCHO), 3.51-4.02 (m, 2H, OCH2), 3.69-3.71 (m, 4H, 2CH2), 3.63-3.64 (m, 4H, 2CH2), 1.51-1.97 (m, 6H, 3CH2).

Workup

  1. customThe organic layer was collected
  2. washwashed with water (100 mL)
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by column chromatography on silica gel using
  7. additiona solvent gradient of a mixture of hexane and ethyl acetate (7/3 and 1/1)

Sources & evidence

ORD record
ord-1750cf983208458e95fa14cf06eb589c
Source dataset
uspto-grants-2000_05
Patent number
US06060472

Reaction notes

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