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

HRID 647011Notes

Reaction equation

HRID 647011 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[C:16]([CH:18]=O)[CH:15]=[CH:14][N:13]=2)[CH2:3][CH2:2]1.[CH3:20][C:21]1[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([NH2:28])[C:22]=1[NH2:29].[CH3:30]N(C=O)C>>[CH3:20][C:21]1[C:22]2[N:29]=[C:18]([C:16]3[CH:15]=[CH:14][N:13]=[C:12]([O:11][CH2:10][CH2:9][CH2:8][CH2:7][CH:4]4[CH2:5][CH2:6][N:1]([CH3:30])[CH2:2][CH2:3]4)[CH:17]=3)[NH:28][C:23]=2[CH:24]=[C:25]([CH3:27])[CH:26]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 3613321(2-Amino-3,5-dimethylphenyl)amineHCID 574347702-(4-Piperidin-4-yl-butoxy)-pyridine-4-carbaldehyde

Product 1

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

Procedure

4,6-Dimethyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole. To a stirred solution of 2-[4-(1-methyl-piperidin-4-yl)-butoxy]-isonicotinonitrile (440 mg, 1.61 mmol, 1.0 equiv) in toluene (5.0 mL) at 0° C. was added 1.0 M diisobutylaluminum hydride in toluene (2.41 mL, 2.41 mmol, 1.5 equiv). After 3 h, methanol (8 mL) and 1.0 M H2SO4 (5 mL) were added. The mixture was stirred for 30 min, and then 1.0 M NaOH (10 mL) was added, followed by satd. aq. sodium potassium tartrate (40 mL) and dichloromethane (100 mL). After stirring for 30 min, the mixture was extracted with chloroform (3×50 mL) and the combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was partially purified by Method 2 to afford 318 mg of a mixture of 2-(4-piperidin-4-yl-butoxy)-pyridine-4-carbaldehyde and several other unidentified products. A portion of the crude of 2-(4-piperidin-4-yl-butoxy)-pyridine-4-carbaldehyde (100 mg), 3,5-dimethyl-benzene-1,2-diamine (70 mg), and Na2S2O5 (93 mg) were stirred in DMF (3 mL) at 90° C. for 18 h. The reaction mixture was loaded directly on silica gel and purified according to Method 2, which afforded 38 mg of the title compound. MS (electrospray): mass calculated for C24H32N4O, 392.26; m/z found 393.4 [M+H]+. 1H NMR (400 MHz, CD3OD): 8.25 (d, J=5.3 Hz, 1H), 7.62 (dd, J=4.5, 1.0 Hz, 1H), 7.48 (s, 1H), 7.24 (s, 1H), 6.95 (s, 1H), 4.34 (t, J=6.6 Hz, 2H), 2.91-2.83 (m, 2H), 2.58 (s, 3H), 2.43 (s, 3H), 2.25 (s, 3H), 2.07-1.95 (m, 2H), 1.86-1.69 (m, 5H), 1.57-1.18 (m, 6H).

Workup

  1. custompurified

Sources & evidence

ORD record
ord-fcfcb011e4484a40b47333307a2a59cb
Source dataset
uspto-grants-2010_04
Patent number
US07705143B2

Reaction notes

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