Triethylamine → HCID 21994305, compound

HRID 1939239Notes

Reaction equation

HRID 1939239 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:6][NH:7][CH2:8][CH:9]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[O:28][CH3:29])[N:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][CH2:11]1.FC(F)(F)C1C=C(C=C(C(F)(F)F)C=1)C(O)=[O:45].C(P(C#N)(CC)=O)C.C(N(CC)CC)C>CN(C=O)C>[CH3:29][O:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[CH:9]([N:10]1[CH2:15][CH2:14][N:13]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:12][CH2:11]1)[CH2:8][NH:7][C:6](=[O:45])[C:5]1[CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=[C:3]([C:2]([F:1])([F:37])[F:38])[CH:4]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 13586794DiethylphosphorylcyanideHCID 15288973HCID 15288973, compound

Product 1

HCID 21994305HCID 21994305, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
3 °C

Procedure

317 mg (1 mmol) of 2-Methoxyphenyl-2-(4-cyclohexylpiperazine-1-yl)-ethylamine (prepared as described in Example 1) are combined with 272 mg (1 mmol) of 3,5-bistrifluoromethylbenzoic acid in 30 ml of DMF. The mixture is cooled to about 3° C. and combined with 501 ml (3.3 mmol) of diethylphosphorylcyanide and 1.4 ml triethylamine. After about 1 hour the ice bath is removed and the mixture is stirred overnight at ambient temperature. It is evaporated down in vacuo and the residue is stirred with a little water and 20% sodium hydrogen carbonate solution. It is suction filtered and washed thoroughly with water. The crude product is chromatographed over silica gel with ethyl acetate/methanol 1:1. The fractions which are uniform according to TLC are combined and freed from solvent in vacuo. The residue is dissolved in a little isopropanol and the N-[2-(2-methoxyphenyl)-2-(4-cyclohexylpiperazine-1-yl)-ethyl]-3,5-bistrifluoromethyl-benzamide is precipitated therefrom in the form of the hydrochloride using ethereal hydrochloric acid and diisopropylether. The product is suction filtered, washed with diisopropylether and dried in vacuo at about 50° C. 200 mg of the substance are obtained as a slightly beige solid (yield 32%).

Workup

  1. customAfter about 1 hour the ice bath is removed
  2. customIt is evaporated down in vacuo
  3. stirringthe residue is stirred with a little water and 20% sodium hydrogen carbonate solution
  4. filtrationfiltered
  5. washwashed thoroughly with water
  6. customThe crude product is chromatographed over silica gel with ethyl acetate/methanol 1:1
  7. dissolutionThe residue is dissolved in a little isopropanol
  8. customthe N-[2-(2-methoxyphenyl)-2-(4-cyclohexylpiperazine-1-yl)-ethyl]-3,5-bistrifluoromethyl-benzamide is precipitated
  9. filtrationfiltered
  10. washwashed with diisopropylether
  11. customdried in vacuo at about 50° C

Sources & evidence

ORD record
ord-2a5fb173326f4708b8fb09e4ddeb1baa
Source dataset
uspto-grants-1997_12
Patent number
US05696123

Reaction notes

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