Triethylamine → HCID 58728658, compound

HRID 1992117Notes

Reaction equation

HRID 1992117 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([CH2:16][CH2:17][N:18]3[CH:23]4[CH2:24][CH2:25][CH:19]3[CH2:20][CH:21]([N:26]3[C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=5[N:28]=[C:27]3[CH3:35])[CH2:22]4)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1[F:36].C(N(CC)CC)C.[CH3:44][C:45]([CH3:50])([CH3:49])[C:46](Cl)=[O:47]>ClCCl>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([CH2:16][CH2:17][N:18]3[C@H:23]4[CH2:24][CH2:25][C@@H:19]3[CH2:20][CH:21]([N:26]3[C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=5[N:28]=[C:27]3[CH3:35])[CH2:22]4)[CH2:15][CH2:14][N:13]([C:46](=[O:47])[C:45]([CH3:50])([CH3:49])[CH3:44])[CH2:12][CH2:11]2)=[CH:6][C:5]=1[F:36]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 68676149HCID 68676149, compound

Product 1

HCID 58728658HCID 58728658, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(8-{2-[4-(4-chloro-3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride (0.20 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-[4-(4-chloro-3-fluorophenyl)-1-(2,2-dimethylpropanoyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole as a white foam (0.11 g, 51%). 1H NMR (400 MHz, CDCl3) δ 7.67 (m, 1H), 7.40 (m, 1H), 7.29 (m, 1H), 7.03-7.19 (m, 4H), 4.72 (m, 1H), 3.90 (m, 2H), 3.33 (m, 4H), 2.59 (s, 3H), 2.42 (m, 2H), 1.78-2.13 (m, 14H), 1.27 (s, 9H). HRMS C33H42ClFN4O m/z 565.3109 (M+H)Cal., 565.3134 (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-10008c8872ed48a0825643badb2db71b
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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