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

HRID 1850786노트

반응식

HRID 1850786 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6212Chloroform용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-f780068952d747828e063fb5b17a9d21
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957062B2

반응 노트

불러오는 중…