Trifluoroacetic acid → 2-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)-6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)quinoxaline

HRID 1471149Notes

Reaction equation

HRID 1471149 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].C(OC([N:15]1[C@H:20]([C:21]2[NH:25][C:24]3[CH:26]=[C:27]([C:30]4[CH:39]=[N:38][C:37]5[C:32](=[CH:33][CH:34]=[C:35]([C:40]6[NH:44][C:43]([C@@H:45]7[CH2:50][C@@H:49]8[C@@H:47]([CH2:48]8)[N:46]7C(OC(C)(C)C)=O)=[N:42][CH:41]=6)[CH:36]=5)[N:31]=4)[CH:28]=[CH:29][C:23]=3[N:22]=2)[CH2:19][C@@H:18]2[C@H:16]1[CH2:17]2)=O)(C)(C)C>C(Cl)Cl>[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[C@@H:16]12[CH2:17][C@@H:18]1[CH2:19][C@@H:20]([C:21]1[NH:25][C:24]3[CH:26]=[C:27]([C:30]4[CH:39]=[N:38][C:37]5[C:32](=[CH:33][CH:34]=[C:35]([C:40]6[NH:44][C:43]([C@@H:45]7[CH2:50][C@@H:49]8[C@@H:47]([CH2:48]8)[NH:46]7)=[N:42][CH:41]=6)[CH:36]=5)[N:31]=4)[CH:28]=[CH:29][C:23]=3[N:22]=1)[NH:15]2

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66981769(1R,3S,5R)-tert-butyl 3-(5-(2-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxalin-6-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 669818562-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)-6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)quinoxalineYield 156.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.25 mL, 3.24 mmol) was added to a solution of (1R,3S,5R)-tert-butyl 3-(5-(2-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxalin-6-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (30 mg, 0.044 mmol) in DCM (0.5 mL) and the mixture was stirred at rt for 16 h. The volatiles were removed under vacuum and the residue was triturated with Et2O to yield a TFA salt of 2-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)-6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)quinoxaline (32.7 mg) as yellow solid. LC-MS retention time 1.33 min; m/z 475 [M+H]+. (Column PHENOMENEX® Luna 3.0×50 mm S10. Solvent A=90% water:10% methanol:0.1% TFA. Solvent B=10% water:90% methanol:0.1% TFA. Flow Rate=4 mL/min. Start % B=0. Final % B=100. Gradient Time=3 min. Wavelength=220). 1H NMR (400 MHz, MeOD) δ ppm 9.47 (s, 1H), 8.54 (s, 1H), 8.50 (s, 1H), 8.31 (dd, J=8.8, 1.8 Hz, 1H), 8.26 (dd, J=8.5, 1.3 Hz, 1H), 8.15 (d, J=8.8 Hz, 1H), 7.83 (s, 1H), 7.82 (d, J=8.8 Hz, 1H), 4.85-4.97 (m, 1H), 4.67 (dd, J=10.8, 7.5 Hz, 1H), 3.45-3.57 (m, 2H), 2.77-2.86 (m, 1H), 2.65-2.74 (m, 1H), 2.52-2.65 (m, 2H), 2.02-2.15 (m, 2H), 1.18-1.30 (m, 2H), 0.95-1.09 (m, 2H).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe residue was triturated with Et2O

Sources & evidence

ORD record
ord-5e1bddce6cda45b9b165085756739f0a
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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