6-Chloro-3-pyridinecarbonitrile → 6-{4-[(4-Cyclobutylhexahydro-1H-1,4-diazepin-1-yl)carbonyl]phenyl}-3-cyanopyridine hydrochloride

HRID 2261237Notes

Reaction equation

HRID 2261237 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C:14]3[CH:19]=[CH:18][C:17](B4OC(C)(C)C(C)(C)O4)=[CH:16][CH:15]=3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[Cl:29][C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][N:31]=1>>[ClH:29].[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C:14]3[CH:15]=[CH:16][C:17]([C:30]4[N:31]=[CH:32][C:33]([C:34]#[N:35])=[CH:36][CH:37]=4)=[CH:18][CH:19]=3)=[O:13])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

3

Reactant 2

HCID 51520946-Chloro-3-pyridinecarbonitrileHCID 66930417(4-Cyclobutylhexahydro-1H-1,4-diazepin-1-yl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone

Product 1

HCID 669303616-{4-[(4-Cyclobutylhexahydro-1H-1,4-diazepin-1-yl)carbonyl]phenyl}-3-cyanopyridine hydrochlorideYield 29.7%

Procedure

The title compound (E12) was prepared in a similar manner to Example 11 from 1-cyclobutyl-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbonyl}hexahydro-1H-1,4-diazepine (D7) (0.15 g) and 6-chloronicotinonitrile (0.054 g). The crude reaction mixture was purified by flash chromatography [silica gel, step gradient 0-15% MeOH (containing 10% 0.88 ammonia solution) in DCM]. The free base compound was converted into the HCl salt in dry DCM (2 ml) with ethereal HCl (1 ml), 1N). Evaporation of solvent afforded the title compound (E12) as a white solid (0.046 g). 1H NMR δ (methanol-d4): 1.78-1.90 (2H, m), 2.1-2.4 (6H, m), 3.03-3.2 (2H, m), 3.5-3.9 (6H, m), 4.28-4.35 (1H, m), 7.65 (2H, d, J=8 Hz), 8.13 (1H, d, J=8 Hz), 8.23-8.26 (3H, m), 8.99 (1H, d, J=2.4 Hz). LCMS electrospray (+ve) 361 (MH+).

Workup

  1. customThe crude reaction mixture
  2. customwas purified by flash chromatography [silica gel, step gradient 0-15% MeOH (containing 10% 0.88 ammonia solution) in DCM]
  3. customEvaporation of solvent

Sources & evidence

ORD record
ord-7df3449aca124822ad09ada3a95dc1c7
Source dataset
uspto-grants-2010_12
Patent number
US07846922B2

Reaction notes

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