Trifluoroacetic acid → HCID 59504642, compound

HRID 2400600Notes

Reaction equation

HRID 2400600 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:21]=[C:20]([C:22]3[CH:26]=[C:25]([CH3:27])[N:24]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=4)[N:23]=3)[O:19][N:18]=2)=[CH:13][CH:12]=1.FC(F)(F)C(O)=O>CN(C=O)C.C(#N)C.O>[CH3:27][C:25]1[N:24]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)[N:23]=[C:22]([C:20]2[O:19][N:18]=[C:17]([C:14]3[CH:13]=[CH:12][C:11]([CH2:10][N:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:16][CH:15]=3)[N:21]=2)[CH:26]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8082PiperidineHCID 24758Sodium hydrideHCID 59504622HCID 59504622, compound

Product 1

HCID 59504642HCID 59504642, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

To a mechanically stirred solution of piperidine (24 mg, 0.28 mmol) in DMF (1.5 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 11.3 mg, 0.28 mmol), and the mixture was stirred at 0° C. for 30 min. 3-[4-(Bromomethyl)phenyl]-5-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazole (Intermediate LL, 100 mg, 0.24 mmol) was added, and the mixture was stirred at rt over night whereupon it was directly subjected to preparative HPLC (RP-18 column; acetonitrile/water gradient containing 0.1% trifluoroacetic acid). The product-containing fractions were combined and the solvent was partly removed. A neutral pH was established by adding saturated aqueous sodium bicarbonate solution, and the mixture was extracted three times with ethyl acetate (20 mL each). The combined organic fractions were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound (62 mg, 61%): 1H-NMR (400 MHz, DMSO-d6) δ 8.01 (d, 2H), 7.50 (d, 2H), 7.17 (d, 2H), 7.12 (d, 2H), 6.90 (s, 1H), 5.42 (s, 2H), 3.50 (s, 2H), 2.42-2.30 (m, 4H), 2.32 (s, 3H), 2.28 (s, 3H), 1.55-1.47 (m, 4H), 1.44-1.35 (m, 2H); ES-MS m/z 428 (MH)+; HPLC RT (Method K) 1.10 min.

Workup

  1. stirringthe mixture was stirred at rt over night whereupon it
  2. customthe solvent was partly removed
  3. additionby adding saturated aqueous sodium bicarbonate solution
  4. extractionthe mixture was extracted three times with ethyl acetate (20 mL each)
  5. dry with materialThe combined organic fractions were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-21138ffeb929493c8b117f04a456008e
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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