Acetic Acid → HCID 59504723, compound

HRID 2400594Notes

Reaction equation

HRID 2400594 reaction equation
C(O)(=O)C.N1C=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:11][C:12]1[N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[N:15]=[C:14]([C:25]2[O:29][N:28]=[C:27]([C:30]3[CH:35]=[CH:34][C:33]([CH2:36][NH2:37])=[CH:32][CH:31]=3)[N:26]=2)[CH:13]=1.COC1CCC(OC)O1>O>[CH3:11][C:12]1[N:16]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=2)[N:15]=[C:14]([C:25]2[O:29][N:28]=[C:27]([C:30]3[CH:31]=[CH:32][C:33]([CH2:36][N:37]4[CH:9]=[CH:8][CH:7]=[CH:6]4)=[CH:34][CH:35]=3)[N:26]=2)[CH:13]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1049PyridineHCID 790982,5-DimethoxytetrahydrofuranHCID 59504732HCID 59504732, compound

Product 1

HCID 59504723HCID 59504723, compoundYield 32.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of acetic acid (348 μL, 6.08 mmol) in water (194 μL) were added successively pyridine (491 μL, 6.08 mmol), 1-(4-{5-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazol-3-yl}phenyl)methanamine (Example 139, 130 mg, 0.362 mmol) and 2,5-dimethoxytetrahydrofuran (47 μL, 0.362 mmol). The reaction mixture was heated to 100° C. for 20 h. After being cooled to rt, water (50 mL) was added, and the mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over anhydrous sodium sulfate. After filtration and evaporation of the solvent, the crude product was first subjected to MPLC (silica, cyclohexane/ethyl acetate 4:1) and then to preparative HPLC affording the title compound as a white solid (48 mg, 31%): NMR (400 MHz, DMSO-d6) 8.02 (d, 2H), 7.35 (d, 2H), 7.18 (d, 2H), 7.11 (d, 2H), 6.91 (s, 1H), 6.86 (t, 2H), 6.05 (t, 2H), 5.42 (s, 2H), 5.21 (s, 2H), 2.32 (s, 3H), 2.27 (s, 3H); ES-MS m/z 410, HPLC RT (Method K) 1.54 min.

Workup

  1. temperatureAfter being cooled to rt
  2. extractionthe mixture was extracted with ethyl acetate (3×30 mL)
  3. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  4. filtrationAfter filtration and evaporation of the solvent

Sources & evidence

ORD record
ord-ddf197f2761842f8adb7639e1b4bceeb
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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