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

HRID 272004ノート

反応式

HRID 272004 の反応式
Cl.Cl.Cl.[CH3:4][C:5]1[N:9]([CH:10]2[CH2:16][C@H:15]3[N:17]([CH2:18][CH2:19][C:20]4([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)[O:25][CH2:24][CH2:23][NH:22][CH2:21]4)[C@H:12]([CH2:13][CH2:14]3)[CH2:11]2)[C:8]2[CH:32]=[CH:33][CH:34]=[CH:35][C:7]=2[N:6]=1.CCN(CC)CC.[CH3:43][C:44]([CH3:49])([CH3:48])[C:45](Cl)=[O:46]>C(Cl)Cl>[CH3:43][C:44]([CH3:49])([CH3:48])[C:45]([N:22]1[CH2:23][CH2:24][O:25][C:20]([CH2:19][CH2:18][N:17]2[C@H:12]3[CH2:13][CH2:14][C@@H:15]2[CH2:16][CH:10]([N:9]2[C:8]4[CH:32]=[CH:33][CH:34]=[CH:35][C:7]=4[N:6]=[C:5]2[CH3:4])[CH2:11]3)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21]1)=[O:46]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 689336682-methyl-1-{(1R,5S)-8-[2-(2-phenylmorpholin-2-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole trihydrochloride

生成物 1

HCID 598359691-((1R,5S)-8-{2-[4-(2,2-dimethylpropanoyl)-2-phenylmorpholin-2-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole収率 107.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 2-methyl-1-{(1R,5S)-8-[2-(2-phenylmorpholin-2-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole trihyrdochloride (65 mg, 0.11 mmol) and Et3N (0.08 mL, 0.55 mmol in 1 mL CH2Cl2 was added trimethylacetyl chloride (0.02 mL, 0.17 mmol), and the reaction was stirred for 24 h. After washing with saturated aqueous NaHCO3, the organic phase was isolated, dried (Na2SO4), concentrated and chromatographed (5% (2M NH3/MeOH) in CHCl3) to afford 1-((1R,5S)-8-{2-[4-(2,2-dimethylpropanoyl)-2-phenylmorpholin-2-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (61 mg, quant.) as a film: 1H NMR (400 MHz, CDCl3), δ 7.68 (m, 1H), 7.45-7.40 (m, 2H), 7.38-7.27 (m, 3H), 7.19-7.11 (m, 2H), 4.77-4.63 (m, 2H), 3.76-3.54 (m, 4H), 3.40-3.20 (m, 3H), 2.59 (s, 3H), 2.48-2.36 (m, 2H), 2.15-1.85 (m, 8H), 1.69-1.59 (m, 2H), 1.19 (s, 9H); ESI-MS 515 (M+H).

後処理

  1. washAfter washing with saturated aqueous NaHCO3
  2. customthe organic phase was isolated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customchromatographed (5% (2M NH3/MeOH) in CHCl3)

出典と根拠

ORDレコード
ord-e9ae0128fd274a21afd294e3314143ce
出典データセット
uspto-grants-2008_11
特許番号
US07452992B2

反応ノート

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