Tetrahydrofuran → 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid-{(R)-1-(3,4-diethyl-benzyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 644323Notes

Reaction equation

HRID 644323 reaction equation
[NH2:1][C@H:2]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH3:26])=[C:21]([CH2:27][CH3:28])[CH:20]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[CH2:7][CH2:6]1)=[O:4].C(N(C(C)C)C(C)C)C.[C:38]1([C:44]2[NH:45][C:46](=[O:55])[N:47]([CH:49]3[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[N:48]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C1C[O:59][CH2:58]C1>>[CH2:27]([C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][C:22]=1[CH2:25][CH3:26])[CH2:18][C@@H:2]([NH:1][C:58]([N:52]1[CH2:51][CH2:50][CH:49]([N:47]2[C:46](=[O:55])[NH:45][C:44]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)=[N:48]2)[CH2:54][CH2:53]1)=[O:59])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[CH2:7][CH2:6]1)=[O:4])[CH3:28]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 11560098(R)-2-amino-3-(3,4-diethyl-phenyl)-1-[4-(1-methylpiperidin-4-yl)-piperazin-1-yl]-propan-1-oneHCID 1356275985-Phenyl-2-piperidin-4-YL-2,4-dihydro-[1,2,4]triazol-3-one

Product 1

HCID 1354745224-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid-{(R)-1-(3,4-diethyl-benzyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide

Procedure

A mixture of 400 mg (1.04 mmol) (R)-2-amino-3-(3,4-diethyl-phenyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-propan-1-one, 205 mg (1.25 mmol) CDT, 0.2 mL (1.15 mmol) ethyldiisopropylamine and 50 mL THF was stirred for 1 h while cooling with an ice bath and stirred for 1 h at RT, then combined with 270 mg (1.11 mmol) 5-phenyl-2-piperidin-4-yl-2,4-dihydro-[1,2,4]triazol-3-one and refluxed for 4 h. The reaction mixture was evaporated down under reduced pressure, the residue was combined with saturated NaHCO3 solution and exhaustively extracted with DCM. The combined organic phases were dried, evaporated down under reduced pressure and the residue was purified by chromatography on silica gel. The product fractions were evaporated down under reduced pressure, the residue was triturated with diisopropylether, suction filtered and dried.

Workup

  1. temperaturewhile cooling with an ice bath
  2. stirringstirred for 1 h at RT
  3. temperaturerefluxed for 4 h
  4. customThe reaction mixture was evaporated down under reduced pressure
  5. extractionexhaustively extracted with DCM
  6. customThe combined organic phases were dried
  7. customevaporated down under reduced pressure
  8. customthe residue was purified by chromatography on silica gel
  9. customThe product fractions were evaporated down under reduced pressure
  10. customthe residue was triturated with diisopropylether, suction
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-4974a1792c8b44b0ae05504382bee047
Source dataset
uspto-grants-2010_04
Patent number
US07700589B2

Reaction notes

Loading…