Lithium Hydroxide → 1-{[1-(4-Furan-3-ylbenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]methyl}cyclopentanecarboxylic acid

HRID 1776756Notes

Reaction equation

HRID 1776756 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:44]=[CH:43][C:9]([CH2:10][N:11]3[C:15]4[CH:16]=[CH:17][C:18]([O:20][CH2:21][C:22]5[CH:31]=[CH:30][C:29]6[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=6)[N:23]=5)=[CH:19][C:14]=4[N:13]=[C:12]3[CH2:32][C:33]3([C:38]([O:40]CC)=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:8][CH:7]=2)=[CH:2]1.C1COCC1.[Li+].[OH-]>CO>[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[CH:8][C:9]([CH2:10][N:11]3[C:15]4[CH:16]=[CH:17][C:18]([O:20][CH2:21][C:22]5[CH:31]=[CH:30][C:29]6[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=6)[N:23]=5)=[CH:19][C:14]=4[N:13]=[C:12]3[CH2:32][C:33]3([C:38]([OH:40])=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:43][CH:44]=2)=[CH:2]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 90416780Ethyl 1-((1-(4-(furan-3-yl)benzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)methyl)cyclopentanecarboxylate

Product 1

HCID 862809891-{[1-(4-Furan-3-ylbenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]methyl}cyclopentanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a 20 mL vial were added ethyl 1-((1-(4-(furan-3-yl)benzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)methyl)cyclopentanecarboxylate (60 mg, 0.1 mmol), THF (1.3 mL) and MeOH (1.3 mL) followed by LiOH (1.4 mL, 1 M). The reaction mixture was heated at 80° C. for 1.5 h. The mixture was cooled to RT and concentrated to dryness. Water (5 mL) was added and the pH was adjusted to ˜5-6 using 1 M HCl. To the mixture was added DCM (5 mL) and the mixture was stirred for 1 h at RT. The organic layer was separated then concentrated to dryness. The resulting residue was purified using FCC or reverse phase HPLC to provide the title compound. MS (ESI): mass calcd. for C35H31N3O4, 557.23; m/z found, 558.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.22 (d, J=8.5, 1H), 8.10 (d, J=8.5, 1H), 7.84 (d, J=8.1, 1H), 7.77-7.69 (m, 3H), 7.58-7.54 (m, 1H), 7.48-7.46 (m, 1H), 7.42 (d, J=8.1, 2H), 7.35-7.34 (m, 1H), 7.16 (d, J=8.8, 1H), 7.04-7.01 (m, 3H), 6.65 (s, 1H), 5.42 (s, 2H), 5.35 (s, 2H), 3.12 (s, 2H), 2.32-2.26 (m, 2H), 1.73-1.68 (m, 2H), 1.65-1.52 (m, 4H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated to dryness
  3. additionWater (5 mL) was added
  4. additionTo the mixture was added DCM (5 mL)
  5. customThe organic layer was separated
  6. concentrationthen concentrated to dryness
  7. customThe resulting residue was purified

Sources & evidence

ORD record
ord-50a64820573445dabc630ed9c1de990a
Source dataset
uspto-grants-2016_02
Patent number
US09265770B2

Reaction notes

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