Iodoethane → HCID 178467650, compound

HRID 1852826Notes

Reaction equation

HRID 1852826 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:24][C@H:25]4[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]4)[C:15]([CH:17]([CH:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)[OH:18])=[N:16][C:12]=3[CH:11]=[C:10]([C:32]#[N:33])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[H-].[Na+].I[CH2:37][CH3:38]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:24][C@H:25]4[CH2:26][CH2:27][C@H:28]([CH3:31])[CH2:29][CH2:30]4)[C:15]([CH:17]([CH:19]4[CH2:20][CH2:21][CH2:22][CH2:23]4)[O:18][CH2:37][CH3:38])=[N:16][C:12]=3[CH:11]=[C:10]([C:32]#[N:33])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 178461198HCID 178461198, compound

Product 1

HCID 178467650HCID 178467650, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-(5-chloropyridin-3-yl)-2-(cyclopentyl(hydroxy)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (240 mg, 0.517 mmol) was dissolved in THF (5.2 mL) and cooled to 0° C. in a flask under nitrogen before adding sodium hydride (41.4 mg, 1.034 mmol). Upon cessation of gas evolution, iodoethane (0.125 μL, 1.552 mmol) was added, and the reaction was allowed to warm to room temperature overnight. 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/0-40% EtOAc) to afford racemic 4-(5-chloropyridin-3-yl)-2-(cyclopentyl(ethoxy)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. The racemic material was then purified by chiral supercritical fluid chromatography (Chiralpak IC, 21×250 mm, 2-Propanol +0.25% Dimethyl Ethyl Amine in CO2) to afford 4-(5-chloropyridin-3-yl)-2-(R)-cyclopentyl(ethoxy)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile and 4-(5-chloropyridin-3-yl)-2-((S)-cyclopentyl(ethoxy)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. 1H NMR (600 MHz, CD3OD) δ 8.78 (d, J=2.3, 1H), 8.75 (d, J=1.5, 1H), 8.29 (t, J=2.0, 1H), 8.24 (s, 1H), 4.65 (d, J=8.5, 1H), 4.08-3.97 (m, 2H), 3.59-3.34 (m, 2H), 2.65-2.54 (m, 1H), 1.88-1.77 (m, 1H), 1.73-1.54 (m, 6H), 1.49 (d, J=13.2, 2H), 1.30-1.25 (m, 1H), 1.17 (t, J=7.0, 3H), 1.15-1.08 (m, 1H), 1.01-0.95 (m, 1H), 0.91-0.76 (m, 4H), 0.75 (d, J=6.6, 3H), 0.56-0.45 (m, 2H). MS ESI calc'd. for C28H34ClN5O [M+H]+ 492. found 492.

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe reaction mixture was quenched with sat. aqueous ammonium chloride
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (hexanes/0-40% EtOAc)

Sources & evidence

ORD record
ord-b7a9e9a2e6024d79bc14f94d068eb335
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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