Cyclopentanecarbaldehyde → HCID 178461198, compound

HRID 1852825Notes

Reaction equation

HRID 1852825 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-].[Cl-].CC1(C)CCCC(C)(C)[N-]1.[Mg+2].[Li+].[CH:41]1([CH:46]=[O:47])[CH2:45][CH2:44][CH2:43][CH2:42]1>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]([CH:46]([CH:41]4[CH2:45][CH2:44][CH2:43][CH2:42]4)[OH:47])=[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 70106CyclopentanecarbaldehydeHCID 25150783Lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichlorideHCID 178461253HCID 178461253, compound

Product 1

HCID 178461198HCID 178461198, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (product of Step 2, Preparative Example 3.1) (500 mg, 1.367 mmol) was dissolved in THF (13.7 mL) and cooled to −78° C. in a flask under nitrogen before adding lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichloride, 1.0 M in THF (3.01 mL, 3.01 mmol). After stirring at −78° C. for 45 minutes, cyclopentanecarbaldehyde (321 μL, 3.01 mmol) was added, and the reaction was allowed to stir at −78° C. for 30 minutes before removing the cooling bath. After warming to room temperature over 1 hr, the reaction mixture was quenched with sat. aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (hexanes/0-65% EtOAc) to afford 4-(5-chloropyridin-3-yl)-2-(cyclopentyl(hydroxy)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C26H30ClN5O [M+H]+ 464. found 464. 1H NMR (600 MHz, CD3OD) δ 8.78 (d, J=2.1, 1H), 8.74 (d, J=1.3, 1H), 8.27-8.24 (m, 1H), 8.23 (s, 1H), 4.68 (d, J=9.1, 1H), 4.15-3.88 (m, 2H), 2.73 (dd, J=8.0, 16.0, 1H), 1.99-1.91 (m, 1H), 1.76-1.54 (m, 6H), 1.50 (d, J=13.3, 2H), 1.31-1.22 (m, 1H), 1.19-1.09 (m, 1H), 1.02-0.96 (m, 1H), 0.92-0.77 (m, 4H), 0.75 (d, J=6.5, 3H), 0.60-0.47 (m, 2H).

Workup

  1. stirringto stir at −78° C. for 30 minutes
  2. custombefore removing the cooling bath
  3. temperatureAfter warming to room temperature over 1 hr
  4. customthe reaction mixture was quenched with sat. aqueous ammonium chloride
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (hexanes/0-65% EtOAc)

Sources & evidence

ORD record
ord-7b32bd6bafaf4be7872fa1c4b1e16c32
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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