Cyanogen Bromide → 4-((1R,2S)-2-(2-(5-(methylsulfonyl)pyridin-2-yloxy)ethyl)cyclopropyl)piperidine-1-carbonitrile

HRID 1850786ノート

反応式

HRID 1850786 の反応式
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[N:9][CH:10]=1)(=[O:4])=[O:3].C(=O)([O-])[O-].[K+].[K+].[N:29]#[C:30]Br>C(Cl)(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][N:20]([C:30]#[N:29])[CH2:19][CH2:18]2)=[N:9][CH:10]=1)(=[O:3])=[O:4]

参加物

5

反応物 3

HCID 10476Cyanogen BromideHCID 11430Potassium CarbonateHCID 708192275-(methylsulfonyl)-2-{2-[(1S,2R)-2-piperidin-4-ylcyclopropyl]ethoxy}pyridine

生成物 1

HCID 867112044-((1R,2S)-2-(2-(5-(methylsulfonyl)pyridin-2-yloxy)ethyl)cyclopropyl)piperidine-1-carbonitrile

試薬・触媒・溶媒 1

HCID 6212Chloroform溶媒

実験手順

5-(Methylsulfonyl)-2-(2-((1S,2R)-2-(piperidin-4-yl)cyclopropyl)ethoxy)pyridine (Step A, Example 11; 310 mg, 0.957 mmol) and potassium carbonate (489 mg, 3.54 mmol) were stirred in chloroform (15 mL). Cyanogen bromide (122 mg, 1.15 mmol) was added. The mixture was stirred at RT for 15 min and refluxed overnight. The mixture was cooled to RT, mixed with silica gel (5 g), and concentrated to dryness under reduced pressure. The residue was loaded on a silica gel column (15 g of silica gel) and eluted with dichloromethane/methanol (99:1, 1 L to provide the title compound as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.71 (dd, J=0.5, 2.5 Hz, 1H), 8.03 (dd, J=2.5, 8.7 Hz, 1H), 6.84 (dd, J=0.6, 8.7 Hz, 1H), 4.48 (t, J=7.2 Hz, 2H), 3.50-3.35 (m, 2H), 3.07 (s, 3H), 3.05-2.90 (m, 2H), 2.15-2.00 (m, 1H), 1.85-1.75 (m, 2H), 1.60-1.35 (m, 3H), 1.00-0.85 (m, 2H), 0.80-0.50 (m, 2H), −0.12 (q, J=5.0 Hz, 1H). MS (Multimode) m/z 339 [M+H]+.

後処理

  1. temperaturerefluxed overnight
  2. temperatureThe mixture was cooled to RT
  3. additionmixed with silica gel (5 g)
  4. concentrationconcentrated to dryness under reduced pressure
  5. washeluted with dichloromethane/methanol (99:1, 1 L

出典と根拠

ORDレコード
ord-f780068952d747828e063fb5b17a9d21
出典データセット
uspto-grants-2015_02
特許番号
US08957062B2

反応ノート

読み込み中…