Dimethylformamide → 2-Bromo-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine

HRID 423701Notes

Reaction equation

HRID 423701 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CS(O[CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[O:25][N:24]=[C:23]([CH:26]([CH3:28])[CH3:27])[N:22]=2)[CH2:17][CH2:16]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[O:25][N:24]=[C:23]([CH:26]([CH3:28])[CH3:27])[N:22]=3)[CH2:17][CH2:16]2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27628652-Bromo-5-hydroxypyridineHCID 57930198(1-(3-Isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonate

Product 1

HCID 866387382-Bromo-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridineYield 80.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-3-pyridinol (1 g, 5.75 mmol), {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl methanesulfonate (prepared as in Example 100, Steps 1-4, 1.74 g, 5.75 mmol), potassium carbonate (1.59 g, 11.49 mmol), and DMF (15 mL) stirred at 80° C. overnight. The mixture was cooled to room temperature, charged with water (100 mL), and was extracted with EtOAc. The organics were dried over MgSO4, filtered, and concentrated. The crude product was purified by chromatography on a silica gel column using 0 to 50% EtOAc/hexane to give 1.76 g (80%) of 2-bromo-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.03 (d, 1H, J=3.1 Hz), 7.36 (d, 1H, J=8.7 Hz), 7.07 (dd, 1H, Ja=8.7 Hz, Jb=3.1 Hz), 4.21 (dd, 2H, Ja=11.0 Hz, Jb=2.1 Hz), 3.84 (d, 2H, J=6.3 Hz), 3.09 (m, 2H), 2.94-2.83 (m, 1H), 2.12-1.98 (m, 1H), 1.92 (d, 2H, J=12.2 Hz), 1.36-1.53 (m, 2H), 1.28 (d, 6H, J=7.0 Hz); LRMS (ESI), m/z 381/383 (M+H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionwas extracted with EtOAc
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-a497d07438f049208531563dfe128ccb
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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