Cyclopentanecarbaldehyde → HCID 178461198、化合物

HRID 81219

反応式

HRID 81219 の反応式
[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

参加物

5

反応物 3

HCID 70106CyclopentanecarbaldehydeHCID 25150783Lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichlorideHCID 178461253HCID 178461253、化合物

生成物 1

HCID 178461198HCID 178461198、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e784fbea9a274ac5af29840baca69d9c
出典データセット
uspto-grants-2014_09
特許番号
US08846657B2

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