Diisopropylethylamine → 1'-(4-Imidazol-1-yl-butyl)-3,3''-dimethyl-1',2',3',4',5',6'-hexahydro-[2,2':6',2'']terpyridine

HRID 1987383Notes

Reaction equation

HRID 1987383 reaction equation
[CH3:1][C:2]1[C:3]([CH:8]2[CH2:13][CH2:12][CH2:11][CH:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Br[CH2:22][CH2:23][CH2:24][CH2:25][N:26]1[CH:30]=[CH:29][N:28]=[CH:27]1.CCN(C(C)C)C(C)C>CN(C=O)C>[N:26]1([CH2:25][CH2:24][CH2:23][CH2:22][N:9]2[CH:8]([C:3]3[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=3)[CH2:13][CH2:12][CH2:11][CH:10]2[C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=2)[CH:30]=[CH:29][N:28]=[CH:27]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 14885696HCID 14885696, compoundHCID 674211653,3''-Dimethyl-1',2',3',4',5',6'-hexahydro-[2,2'; 6',2'']terpyridine

Product 1

HCID 674233861'-(4-Imidazol-1-yl-butyl)-3,3''-dimethyl-1',2',3',4',5',6'-hexahydro-[2,2':6',2'']terpyridineYield 34.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of imidazole (500 mg, 7.35 mmol) and 1,4-dibromobutane (2.6 mL, 22.0) in THF (50 mL) was added 60% NaH (356 mg, 8.81 mmol), and the resultant mixture was refluxed for 2 h and stirred at room temperature overnight. The mixture was quenched with H2O (50 mL) and diluted with CH2Cl2 (75 mL). The aqueous phase was separated and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to dryness. Purification by flash chromatography on silica gel (CH2Cl2/MeOH, 97:3) resulted in partial decomposition of 1-(4-Bromo-butyl)-1H-imidazole. This material was used without any further purification. Using General Procedure A: 3,3″-Dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (94.4 mg, 0.353 mmol), impure 1-(4-Bromo-butyl)-1H-imidazole (145 mg), KI (6.0 mg, 0.035 mmol), DIPEA (0.18 mL, 1.02 mmol), and DMF (3.5 mL) were stirred for 48 h at 60° C. Purification of the crude material by radial chromatography on a 1 mm TLC grade silica gel plate (CH2Cl2/MeOH/NH4OH, 96:2:2) afforded the free base of the title compound (47 mg, 34% over 2 steps) as a colorless oil.

Workup

  1. customThis material was used without any further purification
  2. customPurification of the crude material by radial chromatography on a 1 mm TLC grade silica gel plate (CH2Cl2/MeOH/NH4OH, 96:2:2)

Sources & evidence

ORD record
ord-1a192a0760e84a0c8fc83343148346d4
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

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