Triethylamine → 3-Bromo-5-[1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine

HRID 1521609Notes

Reaction equation

HRID 1521609 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)[CH:5]=[N:6][CH:7]=1.O[N:15]=[C:16]([CH:18]1[CH2:20][CH2:19]1)[NH2:17].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([C:8]2([C:11]3[O:13][N:17]=[C:16]([CH:18]4[CH2:20][CH2:19]4)[N:15]=3)[CH2:9][CH2:10]2)[CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 2794666N'-HydroxycyclopropanecarboximidamideHCID 595784161-(5-Bromopyridin-3-yl)cyclopropane-1-carboxylic acid

Product 1

HCID 899617073-Bromo-5-[1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]pyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the title compound from Example 72 Step A (45 mg, 0.19 mmol), N′-hydroxycyclopropanecarboximidamide (22 mg, 0.22 mmol) and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (116 mg, 0.223 mmol) in N,N-dimethylformamide (0.93 mL) was added triethylamine (26 μl, 0.19 mmol). The reaction stirred at room temperature overnight. It was then diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was then diluted with toluene and heated to reflux overnight. Purification by flash chromatography on silica gel (10-100% ethyl acetate in hexanes) provided the title compound: LCMS m/z 307.85 [M+2+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. additionThe resulting material was then diluted with toluene
  7. temperatureheated
  8. temperatureto reflux overnight
  9. customPurification by flash chromatography on silica gel (10-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-7499308e2ffc41a4bd1c927c130a6870
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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