1-Hydroxybenzotriazole → 5-Thiophen-2-yl-isoxazole-3-carboxylic acid {1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-amide

HRID 1019917Notes

Reaction equation

HRID 1019917 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:10][N:9]=[C:8]([C:11]([OH:13])=O)[CH:7]=1.[CH3:14][O:15][C:16]1[CH:25]=[C:24]2[C:19]([N:20]=[CH:21][C:22]([S:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][CH:32]([NH2:35])[CH2:31][CH2:30]3)=[N:23]2)=[CH:18][CH:17]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:14][O:15][C:16]1[CH:25]=[C:24]2[C:19]([N:20]=[CH:21][C:22]([S:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH:32]([NH:35][C:11]([C:8]4[CH:7]=[C:6]([C:2]5[S:1][CH:5]=[CH:4][CH:3]=5)[O:10][N:9]=4)=[O:13])[CH2:33][CH2:34]3)=[N:23]2)=[CH:18][CH:17]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 31570985-(Thiophen-2-yl)-1,2-oxazole-3-carboxylic acidHCID 667465301-[2-(7-Methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-ylamine

Product 1

HCID 468526925-Thiophen-2-yl-isoxazole-3-carboxylic acid {1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-amideYield 13.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Thiophen-2-yl-isoxazole-3-carboxylic acid (43 mg, 0.22 mmol, 1.0 eq) is added at room temperature to a stirred solution of 1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-ylamine (70 mg, 0.22 mmol, 1.0 eq) in N,N-dimethylformamide (5 mL), followed by 1-hydroxybenzotriazole (32 mg, 0.24 mmol, 1.1 eq), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (47 mg, 0.25 mmol, 1.15 eq) and N,N-diisopropylethylamine (83 μL, 0.48 mmol, 2.25 eq). After 15 hours stirring at room temperature, solvent is evaporated and the residue is extracted with dichloromethane (3×10 mL) and water (10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by preparative HPLC to afford 5-thiophen-2-yl-isoxazole-3-carboxylic acid {1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-amide as an orange solid (15 mg, 13% yield).

Workup

  1. customsolvent is evaporated
  2. extractionthe residue is extracted with dichloromethane (3×10 mL) and water (10 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-1f6cd7c2a4f7405faa656c6b5cd51ec6
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

Loading…