Lithium Hydroxide → HCID 178467594, compound

HRID 81223Notes

Reaction equation

HRID 81223 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:31][CH2:30][C@H:29]([CH3:32])[CH2:28][CH2:27]4)[C:15]([CH:17]([OH:24])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:33]#[N:34])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[OH-].[Li+].I[CH2:38][CH3:39]>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:31][CH2:30][C@H:29]([CH3:32])[CH2:28][CH2:27]4)[C:15]([CH:17]([O:24][CH2:38][CH3:39])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:33]#[N:34])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 6340IodoethaneHCID 178461201HCID 178461201, compound

Product 1

HCID 178467594HCID 178467594, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-2-(hydroxy(phenyl)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (276 mg, 0.585 mmol) in NMP (3 mL) was added lithium hydroxide (28.0 mg, 1.170 mmol) and iodoethane (142 μL, 1.754 mmol), and the reaction mixture was allowed to stir at 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/0-50% EtOAc) to afford racemic 4-(5-chloropyridin-3-yl)-2-(ethoxy(phenyl)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 OJ-H, 21×250 mm, MeOH in CO2) to afford 4-(5-chloropyridin-3-yl)-2-((R)-ethoxy(phenyl)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile and 4-(5-chloropyridin-3-yl)-2-(S)-ethoxy(phenyl)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C29H30ClN5O [M+H]+ 500. found 500. 1H NMR (600 MHz, CD3OD) δ 8.75 (d, J=2.3, 1H), 8.70 (d, J=1.6, 1H), 8.27 (s, 1H), 8.23 (t, J=2.0, 1H), 7.49 (d, J=7.2, 2H), 7.38 (t, J=7.3, 2H), 7.36-7.31 (m, 1H), 5.94 (s, 1H), 4.01-3.85 (m, 2H), 3.68-3.59 (m, 2H), 1.44-1.36 (m, 2H), 1.27 (t, J=7.0, 3H), 1.07-0.98 (m, 1H), 0.89-0.78 (m, 1H), 0.76-0.66 (m, 5H), 0.64-0.54 (m, 1H), 0.54-0.46 (m, 1H), 0.46-0.36 (m, 2H).

Workup

  1. customThe reaction mixture was quenched with sat. aqueous ammonium chloride
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (hexanes/0-50% EtOAc)

Sources & evidence

ORD record
ord-989f487bd63e4a6bb14891cb7913a9a9
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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