Tetrahydrofuran → (3R)-N-methyl-1-({5-[4-methyl-5-(trifluoromethyl)isoxazol-3-yl]thien-2-yl}carbonyl)piperidine-3-carboxamide

HRID 572326Notes

Reaction equation

HRID 572326 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].[CH3:19][NH:20][C:21]([C@@H:23]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]1)=[O:22].C1COCC1>C(N(CC)CC)C>[CH3:19][NH:20][C:21]([C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:13]([C:11]2[S:12][C:8]([C:5]3[C:4]([CH3:16])=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=3)=[CH:9][CH:10]=2)=[O:15])[CH2:24]1)=[O:22]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 7175805(3R)-N-methylpiperidine-3-carboxamide2×HCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 25212207(3R)-N-methyl-1-({5-[4-methyl-5-(trifluoromethyl)isoxazol-3-yl]thien-2-yl}carbonyl)piperidine-3-carboxamideYield 86%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and (3R)-N-methylpiperidine-3-carboxamide (Preparative Example 31) 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 (3R)-N-methylpiperidine-3-carboxamide. After 3 hr the reaction mixture was evaporated in vacuo and filtered with the aid of water. The resulting solids were then washed with a 1 N aqueous HCl solution followed by water. The material was air dried to afford product as a colorless solid (157 mg, 86%). LC/MS 6.00 min, [M+1]+ 402.

Workup

  1. customAfter 3 hr the reaction mixture was evaporated in vacuo
  2. filtrationfiltered with the aid of water
  3. washThe resulting solids were then washed with a 1 N aqueous HCl solution
  4. customdried

Sources & evidence

ORD record
ord-5ec28b1fe71d4189a7cfecaf0cc203e2
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

Loading…