Sodium hydride → 4-Methyl-2-{6-[3-(1-methyl-piperidin-4-yl)-propoxy]-pyridin-3-yl}-1H-benzoimidazole

HRID 646975Notes

Reaction equation

[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][N:13]=2)[CH2:4][CH2:3]1.C[N:21]1[CH2:26][CH2:25][CH:24]([CH2:27][CH2:28][CH2:29]O)CC1.[H-].[Na+].Cl[C:34]1C=CC(C#N)=CN=1>CN(C=O)C>[CH3:34][C:29]1[C:26]2[N:21]=[C:16]([C:15]3[CH:14]=[N:13][C:12]([O:11][CH2:10][CH2:9][CH2:8][CH:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]4)=[CH:19][CH:18]=3)[NH:17][C:25]=2[CH:24]=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 60 °C

Procedure

6-[3-(1-Methyl-Piperidin-4-yl)-propoxy]-nicotinonitrile. To a stirred solution of 3-(1-methyl-piperidin-4-yl)-propan-1-ol (5.0 g, 31.7 mmol, 1.1 equiv) in DMF (200 mL) under an atmosphere of nitrogen, was added 60% sodium hydride (1.73 g, 43.3 mmol, 1.5 equiv) portion wise. Once the initial effervescence had subsided, the mixture was heated at 60° C. for 1 h then cooled to rt. A solution of 6-chloronicotinonitrile (4.0 g, 28.9 mmol, 1.0 equiv) in DMF (20 mL) was then added and the mixture stirred for 16 h. The reaction was quenched with satd. aq. NaHCO3 (50 mL) and brine (50 mL). A precipitate was formed and was collected by vacuum filtration to afford 3.67 g of the desired product. The filtrate was concentrated to half the volume and a second crop of precipitate was collected and combined to give 5.64 g (76%) of an orange solid, which was used without further purification. MS (electrospray): mass calculated for C15H21N3O, 259.17. m/z found, 260.4 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.46 (dd, J=2.3, 0.8 Hz, 1H), 7.77 (dd, J=8.6, 2.3 Hz, 1H), 6.80 (dd, J=8.6, 0.8 Hz, 1H), 4.34 (t, J=6.6 Hz, 2H), 2.96-2.82 (m, 2H), 2.25 (s, 3H), 1.92-1.68 (m, 7H), 1.37-1.34 (m, 2H), 0.89-0.81 (m, 2H).

Workup

temperaturethen cooled to rt
customThe reaction was quenched with satd
customA precipitate was formed
filtrationwas collected by vacuum filtration

Sources & evidence

ORD record: ord-b82d85e09a594e4895abe980a1f30068
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07705149B2

Reaction notes

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