Triethylamine → HCID 58728710, compound

HRID 1992115Notes

Reaction equation

HRID 1992115 reaction equation
Br.[CH3:2][C:3]1[N:7]([CH:8]2[CH2:14][CH:13]3[N:15]([CH2:16][CH2:17][C:18]4([C:24]5[CH:25]=[C:26]([OH:30])[CH:27]=[CH:28][CH:29]=5)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)[CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[C:6]2[CH:31]=[CH:32][CH:33]=[CH:34][C:5]=2[N:4]=1.C(N(CC)CC)C.[CH3:42][C:43]([CH3:48])([CH3:47])[C:44](Cl)=[O:45]>ClCCl>[CH3:42][C:43]([CH3:48])([CH3:47])[C:44]([N:21]1[CH2:20][CH2:19][C:18]([C:24]2[CH:25]=[C:26]([OH:30])[CH:27]=[CH:28][CH:29]=2)([CH2:17][CH2:16][N:15]2[C@H:13]3[CH2:12][CH2:11][C@@H:10]2[CH2:9][CH:8]([N:7]2[C:6]4[CH:31]=[CH:32][CH:33]=[CH:34][C:5]=4[N:4]=[C:3]2[CH3:2])[CH2:14]3)[CH2:23][CH2:22]1)=[O:45]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 68677541HCID 68677541, compound

Product 1

HCID 58728710HCID 58728710, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3-(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-4-yl)phenol hydrobromide (0.22 g, 0.42 mmol), triethylamine (0.117 mL, 0.84 mmol) and trimethylacetyl chloride (0.057 mL, 0.462 mmol) in dichloromethane (2 mL) was stirred at rt for 3 h. The reaction mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate solution, dried, concentrated and purified by chromatography on silica gel eluting with 33:1 dichloromethane:methanol to give 3-(1-(2,2-dimethyl propanoyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-4-yl)phenol as a white solid (0.070 g, 32%). 1H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.47 (m, 1H), 7.34 (m, 1H), 7.05-7.15 (m, 3H), 6.77 (m, 1H), 6.73 (s, 1H), 6.59 (m, 1H), 4.51 (m, 1H), 3.74 (m, 2H), 3.24 (m, 4H), 2.47 (s, 3H), 2.36 (m, 2H), 1.97 (m, 2H), 1.86 (m, 4H), 1.75 (m, 6H), 1.58 (m, 2H), 1.15 (s, 9H). HRMS C33H44N4O2 m/z 529.3543 (M+H)Cal., 529-3542 (M+H)Obs..

Workup

  1. washwashed with saturated sodium bicarbonate solution
  2. customdried
  3. concentrationconcentrated
  4. custompurified by chromatography on silica gel eluting with 33:1 dichloromethane

Sources & evidence

ORD record
ord-1b31d93308d242f6887a88f73d6964ba
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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