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

HRID 1471160Notes

Reaction equation

HRID 1471160 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:31]=[C:32]5[C:37](=[CH:38][CH:39]=4)[N:36]=[C:35]([C:40]4[NH:44][C:43]([C@@H:45]6[CH2:50][C@@H:49]7[C@@H:47]([CH2:48]7)[N:46]6C(OC(C)(C)C)=O)=[N:42][CH:41]=4)[CH:34]=[N:33]5)[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:31]=[C:32]5[C:37](=[CH:38][CH:39]=4)[N:36]=[C:35]([C:40]4[NH:44][C:43]([C@@H:45]6[CH2:50][C@@H:49]7[C@@H:47]([CH2:48]7)[NH:46]6)=[N:42][CH:41]=4)[CH:34]=[N:33]5)[CH:28]=[CH:29][C:23]=3[N:22]=1)[NH:15]2

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66981900(1R,3S,5R)-tert-butyl 3-(5-(6-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxalin-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 669818746-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)-2-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)quinoxalineYield 147.5%

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-(6-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxalin-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (10 mg, 0.015 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. The resulting solid was rinsed with Et2O to yield a TFA salt of 6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)-2-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)quinoxaline (10.5 mg) as yellow solid. LC-MS retention time 1.32 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).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe residue was triturated with Et2O
  3. washThe resulting solid was rinsed with Et2O

Sources & evidence

ORD record
ord-935dfcc5cbb146aebea5ef92db8a4fc8
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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