Piperidine → HCID 131729825, compound

HRID 1409829Notes

Reaction equation

HRID 1409829 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[S:12][C:11]([C:13]([OH:15])=O)=[CH:10][CH:9]=2)[C:4]=1[CH3:16].[ClH:19].Cl.Cl.[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH:29]2[CH2:34][CH2:33][CH2:32][NH:31][CH2:30]2)[CH2:25][CH2:24]1.N1CCCCC1>C(N(CC)CC)C.C1COCC1>[ClH:19].[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH:29]2[CH2:34][CH2:33][CH2:32][N:31]([C:13]([C:11]3[S:12][C:8]([C:5]4[C:4]([CH3:16])=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=4)=[CH:9][CH:10]=3)=[O:15])[CH2:30]2)[CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acidHCID 1317298261124199-57-0

Product 1

HCID 131729825HCID 131729825, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Procedure

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and 1-Methyl-4-piperidin-3-yl-piperazine, tri-hydrochloride by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF solution of triethylamine and piperidine derivative. An additional 3 equivalents of triethylamine was used. The reaction mixture was evaporated to an oil, triturated and filtered with the aid of water, then with a saturated aqueous NaHCO3 solution. The residual oil was then dissolved in EtOAc (2 mL), dried over MgSO4, filtered, and evaporated to an oil. The crude oil was then dissolved in diethyl ether (1 mL) and treated with a 4 N solution of hydrogen chloride in 1,4-dioxane to precipitate product as a colorless solid. The solid was filtered with the aid of diethyl ether and air dried to afford product as a colorless solid (47 mg, 53%). LC/MS 4.62 min, [M+1]+ 443.

Workup

  1. customThe reaction mixture was evaporated to an oil
  2. customtriturated
  3. filtrationfiltered with the aid of water
  4. dissolutionThe residual oil was then dissolved in EtOAc (2 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to an oil
  8. dissolutionThe crude oil was then dissolved in diethyl ether (1 mL)
  9. additiontreated with a 4 N solution of hydrogen chloride in 1,4-dioxane
  10. customto precipitate product as a colorless solid
  11. filtrationThe solid was filtered with the aid of diethyl ether and air
  12. customdried

Sources & evidence

ORD record
ord-d243d199db794439818f50c51ec28865
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

Loading…