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 272004노트

반응식

HRID 272004 반응식
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]

참가 물질

5

반응물 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

생성물 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-benzimidazole수율 107.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e9ae0128fd274a21afd294e3314143ce
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07452992B2

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