HCID 71280491, compound → HCID 71280656, compound

HRID 1497925Notes

Reaction equation

HRID 1497925 reaction equation
[F:1][C:2]1([F:35])[CH2:5][CH:4]([C:6]2[O:10][N:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:34])=[C:15]([NH:17][C:18]([C:20]4[N:24]5[CH:25]=[C:26]([CH2:29][CH2:30][C:31](=[O:33])[CH3:32])[CH:27]=[CH:28][C:23]5=[N:22][CH:21]=4)=[O:19])[CH:16]=3)[N:7]=2)[CH2:3]1.[CH3:36][Mg]Br>C1COCC1>[F:35][C:2]1([F:1])[CH2:5][CH:4]([C:6]2[O:10][N:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:34])=[C:15]([NH:17][C:18]([C:20]4[N:24]5[CH:25]=[C:26]([CH2:29][CH2:30][C:31]([OH:33])([CH3:36])[CH3:32])[CH:27]=[CH:28][C:23]5=[N:22][CH:21]=4)=[O:19])[CH:16]=3)[N:7]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 71280491HCID 71280491, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 71280656HCID 71280656, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamide (F53) (40 mg, 0.083 mmol) in anhydrous THF (2 mL) at −78° C. under a stream of Argon was added methylmagnesium bromide (83 uL, 0.25 mmol). The reaction was stirred to room temperature for 30 minutes. The reaction was cooled to 0° C. and was quenched with saturated NH4Cl (2 mL). The crude product was extracted with ethylacetate. The organic was washed with water, brine and dried over anhydrous sodium sulfate. The solvent was concentrated and the crude product was purified by reverse phase preparative HPLC to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(3-hydroxy-3-methylbutyl)imidazo[1,2-a]pyridine-3-carboxamide (F54). 1H NMR (400 MHz, d6-DMSO) δ 10.18 (s, 1H), 9.36 (s, 1H), 8.68 (s, 1H), 8.08 (d, J=1.6 Hz, 1H), 7.86-7.82 (m, 2H), 7.65-7.62 (m, 1H), 7.51 (d, J=8.4 Hz, 1H), 3.91-3.84 (m, 1H), 3.25-3.04 (m, 4H), 2.78-2.73 (m, 2H), 2.37 (s, 3H), 1.71-1.67 (m, 2H), 1.16 (s, 6H). MS m/z 496.21 (M+1)+.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customwas quenched with saturated NH4Cl (2 mL)
  3. extractionThe crude product was extracted with ethylacetate
  4. washThe organic was washed with water, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationThe solvent was concentrated
  7. customthe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-6c86a82d19264e778771cdc3cb365016
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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