Acetic Acid → racemic 3-[1-(4-Cyanobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]-2,2-dimethylcyclopropanecarboxylic acid

HRID 2178447Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:5]=[CH:4][C:3]=1[NH:20][CH2:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=1.[CH3:30][C:31]1([CH3:39])[C@@H:36]2[C@H:32]1[C:33](=[O:38])[O:34][C:35]2=O.CC(O)=O>C(#N)C>[C:26]([C:25]1[CH:24]=[CH:23][C:22]([CH2:21][N:20]2[C:3]3[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]4[CH:19]=[CH:18][C:17]5[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=5)[N:11]=4)=[CH:7][C:2]=3[N:1]=[C:35]2[CH:36]2[CH:32]([C:33]([OH:38])=[O:34])[C:31]2([CH3:39])[CH3:30])=[CH:29][CH:28]=1)#[N:27]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-(((2-amino-4-(quinolin-2-ylmethoxy)phenyl)amino)methyl)benzonitrile (124 mg, 0.33 mmol) in acetonitrile (3 mL) was added cis-6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (49 mg, 0.33 mmol) and the solution heated to 80° C. for 4 h. AcOH (1 mL) was then added and the heating continued at 80° C. for an additional 16 h. The resulting mixture was cooled to RT and the mixture was concentrated to dryness. The residue purified using FCC to provide 81.4 mg of the title compound. MS (ESI): mass calcd. for C31H26N4O3, 502.20; m/z found, 503.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J=8.6 Hz, 1H), 8.11 (d, J=8.3 Hz, 1H), 7.84 (d, J=8.1 Hz, 1H), 7.78-7.73 (m, 1H), 7.70-7.65 (m, 3H), 7.59-7.54 (m, 1H), 7.33 (d, J=2.3 Hz, 1H), 7.19-7.09 (m, 4H), 5.49-5.39 (m, 4H), 2.32 (d, J=8.3 Hz, 1H), 1.99 (d, J=8.3 Hz, 1H), 1.20 (s, 3H), 1.01 (s, 3H).

Workup

temperatureThe resulting mixture was cooled to RT
concentrationthe mixture was concentrated to dryness
customThe residue purified

Sources & evidence

ORD record: ord-be522d23c39243b783502ea2c244f7b2
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067917B2

Reaction notes

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