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

HRID 1776740Notes

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-9e39f993bb5d4515b7b898bfe482f4ea
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265770B2

Reaction notes

Loading…