HCID 178418573, compound → HCID 178466191, compound

HRID 81225Notes

Reaction equation

HRID 81225 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:26][C@H:27]4[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]4)[C:15]([C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[F:25])=[O:18])=[N:16][C:12]=3[CH:11]=[C:10]([C:34]3[NH:38][C:37](=[O:39])[O:36][N:35]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:40][Mg]Br>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([C:34]3[NH:38][C:37](=[O:39])[O:36][N:35]=3)[CH:11]=[C:12]3[N:16]=[C:15]([C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[F:25])([OH:18])[CH3:40])[N:14]([CH2:26][C@H:27]4[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]4)[C:13]=23)[CH:5]=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 178418573HCID 178418573, compoundHCID 178461199HCID 178461199, compound

Product 1

HCID 178466191HCID 178466191, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 3-{4-(5-chloropyridin-3-yl)-2-[(2-fluorophenyl)carbonyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-d]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one (Example 8.1, 44 mg, 0.08 mmol) in tetrahydrofuran (0.8 mL) at −78° C. was added dropwise methyl magnesium bromide (0.054 mL of 3.0 M in diethyl ether, 0.161 mmol). The reaction was stirred and slowly warmed to −20° C. over 3 hours. The reaction was then quenched via the addition of saturated aqueous ammonium chloride and extracted with ethyl acetate (2×). The combined organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography (0-10% methanol/DCM) to afford 3-{4-(5-chloropyridin-3-yl)-2-[1-(2-fluorophenyl)-1-hydroxyethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-d]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one as a white solid. MS ESI calcd. for C29H28ClFN6O3 [M+H]+ 563. found 563.

Workup

  1. customThe reaction was then quenched via the addition of saturated aqueous ammonium chloride
  2. extractionextracted with ethyl acetate (2×)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified via silica gel chromatography (0-10% methanol/DCM)

Sources & evidence

ORD record
ord-8b7d08e1f0834536b65ba9764210aca9
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

Loading…