Triethylamine → HCID 10119815, compound

HRID 432581Notes

Reaction equation

HRID 432581 reaction equation
[CH3:1][NH:2][C:3](=[O:11])[NH:4][CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[F:12][C:13]([F:43])([F:42])[C:14]1[CH:15]=[C:16]([CH2:24][CH2:25][N:26]([CH3:41])[C:27](=[O:40])[CH:28](OS(C)(=O)=O)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.C(N(CC)CC)C>CC(C)=O>[F:12][C:13]([F:42])([F:43])[C:14]1[CH:15]=[C:16]([CH2:24][CH2:25][N:26]([CH3:41])[C:27](=[O:40])[CH:28]([N:8]2[CH2:7][CH2:6][CH:5]([NH:4][C:3]([NH:2][CH3:1])=[O:11])[CH2:10][CH2:9]2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:17]=[C:18]([C:20]([F:22])([F:23])[F:21])[CH:19]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12019500HCID 12019500, compoundHCID 18759970HCID 18759970, compound

Product 1

HCID 10119815HCID 10119815, compoundYield 32.8%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

6.8 g of 4-(3-methylureido)-piperidine are refluxed together with 19.2 g of N-[2-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-2-methanesulphonyloxy-N-methyl-2-phenyl-acetamide (prepared analogously to the method described in WO 99/62893) and 6.8 ml of triethylamine in 400 ml of acetone for 8 hours. Then the solution is evaporated down, combined with saturated sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract is dried, the solvent is eliminated in vacuo and the residue is chromatographed with methylene chloride/methanol 9:1 over silica gel. The fractions found to be uniform by TLC are combined and the solvent is eliminated in vacuo. N-[2-(3,5-bis-tifluormethyl-phenyl)-ethyl]-N-methyl-2-[4-(3-methyl-ureido)-piperidin-1-yl]-2-phenyl-acetamide is crystallised from the residue with ethanolic hydrochloric acid and ether in the form of the hydrochloride, yielding 7.1 g of colourless crystals. 1H-NMR (250 MHz, CD3OD) δppm=7.93-7.33 (8H, m); 5.58; 5.38 (1H, 2s); 4.03-2.59 (5H, m); 3.05 (4H, m); 2.98; 2.90 (3H, 2s); 2.74; 2.70 (3H, 2s); NH in the solvent blind peak 4.89; 2.27-1.52 (4H, m). Most signals are split by amide rotation.

Workup

  1. customprepared analogously to the method
  2. customfor 8 hours
  3. customThen the solution is evaporated down
  4. extractionextracted with ethyl acetate
  5. customThe extract is dried
  6. customthe residue is chromatographed with methylene chloride/methanol 9:1 over silica gel
  7. customN-[2-(3,5-bis-tifluormethyl-phenyl)-ethyl]-N-methyl-2-[4-(3-methyl-ureido)-piperidin-1-yl]-2-phenyl-acetamide is crystallised from the residue with ethanolic hydrochloric acid and ether in the form of the hydrochloride

Sources & evidence

ORD record
ord-7a3ebf3077a149589cdd37c74f9895bf
Source dataset
uspto-grants-2003_12
Patent number
US06664253B2

Reaction notes

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