Sodium hydride → 4,6-Dimethyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole

HRID 646980Notes

Reaction equation

HRID 646980 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][N:20]=2)[C:16]#[N:17])[CH2:4][CH2:3]1.C[N:22]1[CH2:27][CH2:26][CH:25]([CH2:28][CH2:29][CH2:30][CH2:31]O)CC1.[H-].[Na+].Cl[C:36]1C=C(C=CN=1)C#N.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[CH3:31][C:30]1[C:27]2[N:22]=[C:16]([C:15]3[CH:18]=[CH:19][N:20]=[C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][CH:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)[CH:14]=3)[NH:17][C:26]=2[CH:25]=[C:28]([CH3:36])[CH:29]=1

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 5686382-Chloro-4-cyanopyridineHCID 230339654-(1-Methyl-piperidin-4-yl)-butan-1-olHCID 574528642-[4-(1-Methyl-piperidin-4-yl)-butoxy]-isonicotinonitrile

Product 1

HCID 442538274,6-Dimethyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazoleYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

2-[4-(1-Methyl-piperidin-4-yl)-butoxy]-isonicotinonitrile. To a solution of 4-(1-methyl-piperidin-4-yl)-butan-1-ol (1.0 g, 5.85 mmol, 1.0 equiv) in DMF (25 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 0.28 g, 7.02 mmol, 1.2 equiv). The mixture was warmed to rt and stirred for 1 h. The mixture was then re-cooled to 0° C. and a solution of 2-chloro-isonicotinonitrile (0.81 g, 5.85 mmol, 1.0 equiv) in DMF (10 mL) was added dropwise. The mixture was stirred at rt for 18 h, then was diluted with water (25 mL) and satd. aq. NaHCO3 (100 mL). The mixture was extracted with chloroform (3×100 mL), and the combined extracts were concentrated. Purification by Method 2 afforded 0.44 g (28%) of title compound. MS (electrospray): mass calculated for C16H23N3O, 273.18. m/z found, 274.4 [M+H]+. 1H NMR (400 MHz, CD3OD): 8.28 (dd, J=5.2, 0.7 Hz, 1H), 7.05 (dd, J=5.2, 1.3 Hz, 1H), 6.99-6.95 (m, 1H), 4.21 (t, J=6.6 Hz, 2H), 2.88-2.79 (m, 2H), 2.26 (s, 3H), 1.95-1.83 (m, 2H), 1.81-1.59 (m, 4H), 1.51-1.38 (m, 2H), 1.34-1.16 (m, 5H).

Workup

  1. temperatureThe mixture was then re-cooled to 0° C.
  2. stirringThe mixture was stirred at rt for 18 h
  3. extractionThe mixture was extracted with chloroform (3×100 mL)
  4. concentrationthe combined extracts were concentrated
  5. customPurification by Method 2

Sources & evidence

ORD record
ord-419445fd1dfe440c825b2bb842f68bb2
Source dataset
uspto-grants-2010_04
Patent number
US07705149B2

Reaction notes

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