Potassium Carbonate → But-2-ynyl 4-[4-[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-benzimidazol-1-yl]-1-piperidyl]-4-methyl-piperidine-1-carboxylate

HRID 1642500ノート

反応式

HRID 1642500 の反応式
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@H:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]4[NH:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Cl[C:31]([O:33][CH2:34][C:35]#[C:36][CH3:37])=[O:32]>O.ClCCl>[O:23]=[C:15]1[N:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:2]3([CH3:1])[CH2:7][CH2:6][N:5]([C:31]([O:33][CH2:34][C:35]#[C:36][CH3:37])=[O:32])[CH2:4][CH2:3]3)[CH2:9][CH2:10]2)[C@H:18]2[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]2[NH:16]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 41316692-Butyn-1-yl chloroformateHCID 57619802(3aS,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

生成物 1

HCID 25221447But-2-ynyl 4-[4-[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-benzimidazol-1-yl]-1-piperidyl]-4-methyl-piperidine-1-carboxylate収率 7.59%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of (3aS,7aS)-3-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-1H-benzimidazol-2-one (HCl salt, 0.4105 g, 1.15 mmol) and potassium carbonate (0.170 g, 1.23 mmol) in water (3.00 mL) was added a solution of but-2-ynyl chloroformate (0.156 mL, 1.38 mmol) in dichloromethane (3 mL). The reaction mixture was stirred at room temperature overnight. The mixture was poured into hydrometrix varian column chem elut catridge column and rinsed with dichloromethane (3 Column volumes). Concentrated in vacuo and the residue was purified by flash chromatography (0 to 50% MeOH/Ethyl acetate) and followed by preparative LC/MS (high pH) to give the title compound (0.036 g, 7.59%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1H NMR (400 MHz, CDCl3) δ ppm 1.30-1.47 (m, 6H), 1.49 (s, 2H), 1.62-1.76 (m, 1H), 1.76-2.00 (m, 9H), 2.34 (s, 2H), 2.72-2.98 (m, 6H), 2.99-3.09 (m, 2H), 3.49-3.85 (m, 2H), 4.11 (s, 1H), 4.27 (s, 2H), 4.49 (s, 1H), 4.61-4.72 (m, 2H) MS (M+1): 417.3.

後処理

  1. additionThe mixture was poured into hydrometrix varian column chem elut catridge column
  2. washrinsed with dichloromethane (3 Column volumes)
  3. concentrationConcentrated in vacuo
  4. customthe residue was purified by flash chromatography (0 to 50% MeOH/Ethyl acetate)

出典と根拠

ORDレコード
ord-ae3371726be84aecaae6f1cc7b2d718c
出典データセット
uspto-grants-2012_02
特許番号
US08119661B2

反応ノート

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