Methoxyacetone → HCID 178495539, compound

HRID 81231Notes

Reaction equation

HRID 81231 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:17][C@H:18]4[CH2:23][CH2:22][C@H:21]([CH3:24])[CH2:20][CH2:19]4)[CH:15]=[N:16][C:12]=3[CH:11]=[C:10]([C:25]#[N:26])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[Cl-].[Li+].CC1(C)CCCC(C)(C)N1[Mg]Cl.[CH3:41][O:42][CH2:43][C:44](=[O:46])[CH3:45]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:17][C@H:18]4[CH2:23][CH2:22][C@H:21]([CH3:24])[CH2:20][CH2:19]4)[C:15]([C:44]([OH:46])([CH3:45])[CH2:43][O:42][CH3:41])=[N:16][C:12]=3[CH:11]=[C:10]([C:25]#[N:26])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 22172MethoxyacetoneHCID 178424953HCID 178424953, compoundHCID 178461253HCID 178461253, compound

Product 1

HCID 178495539HCID 178495539, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, Step 2) (350 mg, 0.95 mmol) was dissolved in THF (10 mL) and cooled to −78° C. 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex (Aldrich, 1M in THF/toluene) (2.0 mL, 2.0 mmol) was added slowly to the solution at −78° C. The reaction was stirred at −78° C. for 2 hours. Then methoxyacetone (168 mg, 2.0 mmol) was added into the reaction mixture at −78° C. The reaction was allowed to warm to room temperature and stirred for 8 hours under a nitrogen atmosphere. The reaction was quenched with saturated NH4Cl solution (5 mL) at −78° C. and extracted with EtOAc (2×10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on a silica gel column (0 to 100% EtOAc/hexanes) to afford 4-(5-chloropyridin-3-yl)-2-(2-hydroxy-1-methoxypropan-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS APCl calcd. for C24H28ClN5O2 [M+H]+ 454. found 454.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 8 hours under a nitrogen atmosphere
  3. customThe reaction was quenched with saturated NH4Cl solution (5 mL) at −78° C.
  4. extractionextracted with EtOAc (2×10 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on a silica gel column (0 to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e1a17ee3f889489f9302403d6a0540b7
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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