4-Vinylpyridine → 5-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

HRID 1780361노트

반응식

HRID 1780361 반응식
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][N:12]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][C:7]=1[Cl:8].[CH:22]([C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1)=[CH2:23].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:27]1[CH:28]=[CH:29][C:24]([CH:22]=[CH:23][C:2]2[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]3[CH2:14][CH2:13][N:12]3[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][C:7]=2[Cl:8])=[CH:25][CH:26]=1

참가 물질

7

반응물 4

HCID 75024-VinylpyridineHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 228726673-(1-BOC-2-(S)-azetidinylmethoxy)-5-bromo-6-chloropyridine

생성물 1

HCID 538519835-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine수율 35%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6342Acetonitrile용매

실험 절차

To a solution of 5-bromo-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from Example 66a (470 mg, 1.25 mmol) in acetonitrile (6.2 mL) was added 4-vinylpyridine (0.17 mL, 1.57 mmol), palladium acetate (26.0 mg, 0.11 mmol), tri-o-tolylphosphine (130 mg, 0.1 mmol) and triethylamine (2.6 mL). The reaction mixture was heated at reflux overnight, then cooled to room temperature. The solvent was removed, and the residue was chromatographed on a silica gel column, eluting with ethyl acetate:hexane 1:1 to 3:1 to afford the title compound (176 mg, 35% yield). MS (CI/NH3) m/z 402 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.42 (s, 9H), 2.27-2.43 (m, 2H), 3.86-3.95 (m, 2H), 4.27-4.24 (m, 1H), 4.36-4.67 (m, 1H), 4.50-4.60 (m, 1H), 7.07 (d, J=11, 1H), 7.41-7.47 (m, 4H), 7.57 (d, J=11, 1H), 7.58-7.65 (m, 1H), 8.09 (d, J=2, 1H), 8.61-8.68 (m, 2H).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customThe solvent was removed
  4. customthe residue was chromatographed on a silica gel column
  5. washeluting with ethyl acetate:hexane 1:1 to 3:1

출처 및 근거

ORD 기록
ord-6381875492d74e8381a8778f5b01aa4c
출처 데이터셋
uspto-grants-1997_05
특허 번호
US05629325

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