Triethylamine → HCID 58728230, compound

HRID 1992112Notes

Reaction equation

HRID 1992112 reaction equation
Cl.Cl.[CH2:3]([O:5][C:6]1[CH:7]=[C:8]([C:12]2([CH2:18][CH2:19][N:20]3[CH:25]4[CH2:26][CH2:27][CH:21]3[CH2:22][CH:23]([N:28]3[C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=5[N:30]=[C:29]3[CH3:37])[CH2:24]4)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:9]=[CH:10][CH:11]=1)[CH3:4].C(N(CC)CC)C.[CH3:45][C:46]([CH3:51])([CH3:50])[C:47](Cl)=[O:48]>ClCCl>[CH3:45][C:46]([CH3:51])([CH3:50])[C:47]([N:15]1[CH2:16][CH2:17][C:12]([CH2:18][CH2:19][N:20]2[C@H:21]3[CH2:27][CH2:26][C@@H:25]2[CH2:24][CH:23]([N:28]2[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[N:30]=[C:29]2[CH3:37])[CH2:22]3)([C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:3][CH3:4])[CH:7]=2)[CH2:13][CH2:14]1)=[O:48]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 68676165HCID 68676165, compound

Product 1

HCID 58728230HCID 58728230, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(8-{2-[4-(3-ethoxyphenyl) piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride (0.2 g, 0.39 mmol), triethylamine (0.11 mL, 0.78 mmol) and trimethylacetyl chloride (0.053 mL, 0.43 mmol) in dichloromethane (4 mL) was stirred at rt for 1 h before the reaction mixture was quenched with saturated sodium bicarbonate solution. The organic layer was separated, dried, concentrated and purified by chromatography on silica gel eluting with a dichloromethane to 1:9 methanol:dichloromethane gradient to give 1-((1R,5S)-8-{2-[1-(2,2-dimethylpropanoyl)-4-(3-ethoxyphenyl) piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole as a foam (0.14 g, 65%). 1H NMR (400 MHz, CDCl3) δ 7.65 (m, 1H), 7.28 (m, 2H), 7.16 (m, 2H), 6.86 (m, 2H), 6.76 (m, 1H), 4.63 (m, 1H), 4.04 (m, 2H), 3.94 (m, 2H), 3.29 (m, 4H), 2.59 (s, 3H), 2.40 (m, 2H), 2.19 (m, 2H), 1.66-1.95 (m, 12H), 1.43 (t, 3H), 1.26 (s, 9H). HRMS C35H48N4O2 m/z 557.3856 (M+H)Cal., 557.3840 (M+H)Obs..

Workup

  1. customwas quenched with saturated sodium bicarbonate solution
  2. customThe organic layer was separated
  3. customdried
  4. concentrationconcentrated
  5. custompurified by chromatography on silica gel eluting with a dichloromethane to 1:9 methanol

Sources & evidence

ORD record
ord-7b0ce4dfe0ec4f319ac0c0dea41e89b7
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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