HCID 71281072, compound → HCID 71281342, compound

HRID 405854Notes

Reaction equation

HRID 405854 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:16][N:15]([C:17]([O:19][CH3:20])=[O:18])[CH2:14]3)[O:10][N:9]=2)=[CH:4][C:3]=1[NH:21][C:22]([C:24]1[N:28]2[CH:29]=[C:30]([CH2:33][CH2:34][C:35](=[O:37])[CH3:36])[CH:31]=[CH:32][C:27]2=[N:26][CH:25]=1)=[O:23].[CH3:38][Mg]Br>C1COCC1>[OH:37][C:35]([CH3:38])([CH3:36])[CH2:34][CH2:33][C:30]1[CH:31]=[CH:32][C:27]2[N:28]([C:24]([C:22]([NH:21][C:3]3[CH:4]=[C:5]([C:8]4[N:12]=[C:11]([CH:13]5[CH2:14][N:15]([C:17]([O:19][CH3:20])=[O:18])[CH2:16]5)[O:10][N:9]=4)[CH:6]=[CH:7][C:2]=3[CH3:1])=[O:23])=[CH:25][N:26]=2)[CH:29]=1

Participants

4

Reactant 2

HCID 71281072HCID 71281072, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 71281342HCID 71281342, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of methyl 3-(3-(4-methyl-3-(6-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F65) (10 mg, 0.0199 mmol) in anhydrous THF (1 mL) at −78° C. under a stream of Argon was added methylmagnesium bromide (27 uL, 0.080 mmol). The reaction was stirred to room temperature for 15 minutes then cooled to 0° C. and quenched with 1N HCl. The crude product was purified by reverse phase preparative HPLC to give methyl 3-(3-(3-(6-(3-hydroxy-3-methylbutyl)imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F67). 1H NMR (400 MHz, d6-DMSO) δ 10.10 (s, 1H), 9.34 (s, 1H), 8.63 (s, 1H), 8.10 (d, J=1.6 Hz, 1H), 7.84 (dd, J=1.6, 8.0 Hz, 1H), 7.78 (d, J=9.2 Hz, 1H), 7.56-7.54 (m, 1H), 7.51 (d, J=8.4 Hz, 1H), 4.39-4.34 (m, 2H), 4.31-4.25 (m, 1H), 4.22-4.17 (m, 2H), 3.59 (s, 3H), 2.76-2.72 (m, 2H), 2.37 (s, 3H), 1.71-1.67 (m, 2H), 1.15 (s, 6H). MS m/z 519.23 (M+1)+.

Workup

  1. temperaturethen cooled to 0° C.
  2. customquenched with 1N HCl
  3. customThe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-a3e2c1c8cfd84881a12543dcc797cf41
Source dataset
uspto-grants-2014_06
Patent number
US08754071B2

Reaction notes

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