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Triethylamine → 1-((1R,5S)-8-{2-[1-(2-furoyl)-4-phenylpiperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole

HRID 1992061
ノート
印刷プレビュー

反応式

HRID 1992061 の反応式
Cl.Cl.[CH3:3][C:4]1[N:8]([CH:9]2[CH2:15][CH:14]3[N:16]([CH2:17][CH2:18][C:19]4([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1.C(N(CC)CC)C.[O:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[C:47](Cl)=[O:48]>ClCCl>[O:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[C:47]([N:22]1[CH2:21][CH2:20][C:19]([CH2:18][CH2:17][N:16]2[C@H:14]3[CH2:13][CH2:12][C@@H:11]2[CH2:10][CH:9]([N:8]2[C:7]4[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=4[N:5]=[C:4]2[CH3:3])[CH2:15]3)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:24][CH2:23]1)=[O:48]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 8471TriethylamineHCID 682422-Furancarbonyl chlorideHCID 686757782-methyl-1-{8-[2-(4-phenyl piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride

生成物 1

HCID 587280631-((1R,5S)-8-{2-[1-(2-furoyl)-4-phenylpiperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole収率 86%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

実験手順

To a stirred solution of endo 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride II (0.35 g, 0.69 mmol) in dichloromethane (7 mL) and triethylamine (0.209 g, 2.07 mmol) was added 2-furoyl chloride (0.094 g, 0.72 mmol) at 0° C. The ice bath was then removed and the mixture allowed to stir for 30 min. The solvents were then removed in vacuo and the solid was added ethyl acetate and water. The insoluble precipitate was then filtered off and subsequently characterized as the desired product 19. Additional 0.18 g of the desired product 19 was obtained by extracting the organic layer with water (3×), drying with magnesium sulfate and evaporating solvents in vacuo. Following the SFC purification, on a portion of crude 19, 60 mg of the desired product 1-((1R,5S)-8-{2-[1-(2-furoyl)-4-phenylpiperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole 19 was obtained (calculated yield 86%). 1H NMR (400 MHz, CD3OD) δ 7.57 (1H, dist. d, J=1.1 Hz), 7.47 (1H, d, J=7.1 Hz), 7.43-7.29 (5H, m), 7.26-7.09 (3H, m), 6.89 (1H, d, J=3.6 Hz), 6.48 (1H, dd, J=1.8, 3.6 Hz), 4.08 (2H, m), 3.84 (2H, m), 2.60 (5H, m), 2.42 (3H, s), 2.30 (2H, m), 2.20 (2H, m), 2.05 (7H, m), 1.83 (2H, m). HRMS m/z (M+H)+Calc 523.3062; (M+H)+Obs 523.3073.

後処理

  1. customThe ice bath was then removed
  2. customThe solvents were then removed in vacuo
  3. additionthe solid was added ethyl acetate and water
  4. filtrationThe insoluble precipitate was then filtered off

出典と根拠

ORDレコード
ord-36d7d102287a4c418b7f5a5c498ab74e
出典データセット
uspto-grants-2010_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07645771B2

反応ノート

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