Hydrochloric Acid → 3-[5-(3-Hydroxy-8-aza-bicyclo[3.2.1]octane-8-carbonyl)-benzoimidazol-1-yl]-propionitrile
Reaction equation
[C:1]([CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]([OH:16])=O)=[CH:13][C:8]=2[N:7]=[CH:6]1)#[N:2].C1C=CC2N(O)N=NC=2C=1.Cl.CC[N:30]([CH:34]([CH3:36])[CH3:35])[CH:31]([CH3:33])[CH3:32].CCN=C=NCCCN(C)C.Cl.CN([CH:52]=[O:53])C>>[OH:53][CH:52]1[CH2:35][CH:34]2[N:30]([C:14]([C:12]3[CH:11]=[CH:10][C:9]4[N:5]([CH2:4][CH2:3][C:1]#[N:2])[CH:6]=[N:7][C:8]=4[CH:13]=3)=[O:16])[CH:31]([CH2:32][CH2:36]2)[CH2:33]1Participants
7
Reactant 6
Product 1
Procedure
To a solution of 1-(2-cyanoethyl)-1H-benzoimidazole-5-carboxylic acid (0.25 g, 1.16 mmol) in DMF (2.5 mL) was added with stirring HOBt (0.17 g, 1.27 mmol) followed by exo-nortropinol hydrochloride (0.21 g, 1.27 mmol), DIPEA (0.45 g, 3.48 mmol). EDCl.HCl was then added and it was stirred at room temperature for 12 h. The solvent was then evaporated and to the residue diluted with water (5 mL) and extracted with CH2Cl2. The organic phase was washed with brine solution, dried (Na2SO4) and the solvent evaporated. The residue was purified by preparative HPLC which afforded 0.26 g (67%) of 3-[5-(3-Hydroxy-8-aza-bicyclo[3.2.1]octane-8-carbonyl)-benzoimidazol-1-yl]-propionitrile. MS-ESI m/z 325 (M+1).
Workup
- customThe solvent was then evaporated and to the residue
- additiondiluted with water (5 mL)
- extractionextracted with CH2Cl2
- washThe organic phase was washed with brine solution
- dry with materialdried (Na2SO4)
- customthe solvent evaporated
- customThe residue was purified by preparative HPLC which
Sources & evidence
- ORD record
- ord-70da5a04389a435099296b11e06fea50
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08053431B2
Reaction notes
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