Methanesulfonyl chloride → 6-bromo-N-(5-(5-((3-cyanoazetidin-1-yl)methyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 405835Notes

Reaction equation

HRID 405835 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20]4[N:24]=[C:23]([CH2:25]O)[O:22][N:21]=4)[CH:17]=[CH:16][C:15]=3[CH3:27])=[O:12])=[CH:9][N:10]=2)[CH:7]=1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.[NH:42]1[CH2:45][CH:44]([C:46]#[N:47])[CH2:43]1>ClCCl.CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20]4[N:24]=[C:23]([CH2:25][N:42]5[CH2:45][CH:44]([C:46]#[N:47])[CH2:43]5)[O:22][N:21]=4)[CH:17]=[CH:16][C:15]=3[CH3:27])=[O:12])=[CH:9][N:10]=2)[CH:7]=1

Participants

8

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 221323843-AzetidinecarbonitrileHCID 712806916-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 712807916-bromo-N-(5-(5-((3-cyanoazetidin-1-yl)methyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 6-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (142) (200 mg, 0.47 mmol) and DIEA (0.25 mL, 1.41 mmol) in dichloromethane (5 mL) was added MsCl (108.1 mg, 0.94 mmol). The mixture was stirred at room temperature for 10 minutes and then diluted with dichloromethane (10 mL) and washed with water. The organic layers were dried over Na2SO4, filtered and concentrated to give a residue which was dissolved in DMF (2 mL). Then azetidine-3-carbonitrile (116 mg, 1.41 mmol) was added and the reaction mixture was heated at 80° C. for 1 hour. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated to give the crude product which was purified by silica chromatography to yield 6-bromo-N-(5-(5-((3-cyanoazetidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (143). 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 9.62 (dd, J=0.8, 2.0 Hz, 1H), 8.60 (s, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.83 (dd, J=1.6, 8.0 Hz, 1H), 7.79 (dd, J=0.8, 9.6 Hz, 1H), 7.68 (dd, J=2.0, 9.6 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 4.06 (s, 2H), 3.67 (m, 2H), 3.51-3.60 (m, 3H), 2.37 (s, 3H). MS m/z 492.0, 494.0 (M+1)+.

Workup

  1. washwashed with water
  2. dry with materialThe organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue which
  6. temperaturethe reaction mixture was heated at 80° C. for 1 hour
  7. extractionextracted with EtOAc
  8. dry with materialThe organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product which
  12. customwas purified by silica chromatography

Sources & evidence

ORD record
ord-96d756ff8857411988a57eaaf0d7c0e5
Source dataset
uspto-grants-2014_06
Patent number
US08754071B2

Reaction notes

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