Ethanesulfonyl chloride → N-(5-(5-(1-(ethylsulfonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 570359Notes

Reaction equation

HRID 570359 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14]3)[O:10][N:9]=2)=[CH:4][C:3]=1[NH:24][C:25]([C:27]1[N:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]2=[N:29][CH:28]=1)=[O:26].CCN(C(C)C)C(C)C.[CH2:45]([S:47](Cl)(=[O:49])=[O:48])[CH3:46]>C(O)(C(F)(F)F)=O>[CH2:45]([S:47]([N:15]1[CH2:14][CH:13]([C:11]2[O:10][N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[C:3]([NH:24][C:25]([C:27]4[N:31]5[CH:32]=[CH:33][CH:34]=[CH:35][C:30]5=[N:29][CH:28]=4)=[O:26])[CH:4]=3)[N:12]=2)[CH2:16]1)(=[O:49])=[O:48])[CH3:46]

Participants

5

Reactant 3

HCID 11667Ethanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 71281163Tert-butyl 3-(3-(4-fluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

Product 1

HCID 71281188N-(5-(5-(1-(ethylsulfonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Tert-butyl 3-(3-(4-fluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F27) (14.4 mg, 0.03 mmol) was dissolved in TFA (0.5 mL) and stirred at room temperature for 10 minutes. Then TFA was removed under vacuum. The residue was dissolved in anhydrous dichloromethane (1 mL) and DIEA (13.0 mg, 0.10 mmol) and ethanesulfonyl chloride (5.8 mg, 0.045 mmol) were added. The reaction was stirred at room temperature for 10 minutes. The solvent was removed and the crude was purified by preparative HPLC to afford N-(5-(5-(1-(ethylsulfonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (F28). 1H NMR (400 MHz, CDCl3) δ 9.50 (d, J=2 Hz, 1H), 9.09 (dd, J=2, 7.2 Hz, 1H), 8.21 (s, 1H), 7.87 (m, 1H), 7.79 (m, 1H), 7.71 (d, J=9.2 Hz, 1H), 7.41 (m, 1H), 7.22 (dd, J=8.8, 10.4 Hz, 1H), 7.02 (dt, J=0.8, 6.8 Hz, 1H), 4.34 (m, 4H), 4.07 (m, 1H), 3.00 (q, J=7.6 Hz, 2H), 1.35 (t, J=7.6 Hz, 3H). MS m/z 471.1 (M+1)+.

Workup

  1. customThen TFA was removed under vacuum
  2. dissolutionThe residue was dissolved in anhydrous dichloromethane (1 mL)
  3. stirringThe reaction was stirred at room temperature for 10 minutes
  4. customThe solvent was removed
  5. customthe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-a19690117d3640f6a3e4189b01c7ff7c
Source dataset
uspto-grants-2015_05
Patent number
US09023839B2

Reaction notes

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