Trifluoroacetic acid → HCID 66982147, compound

HRID 1471131Notes

Reaction equation

HRID 1471131 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[CH:61]=[CH:60][C:43]7[NH:44][C:45]([C@@H:47]8[CH2:52][C@@H:51]9[C@@H:49]([CH2:50]9)[N:48]8C(OC(C)(C)C)=O)=[N:46][C:42]=7[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[CH:61]=[CH:60][C:43]7[N:44]=[C:45]([C@@H:47]8[CH2:52][C@@H:51]9[C@@H:49]([CH2:50]9)[NH:48]8)[NH:46][C:42]=7[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 acid2×HCID 178452518HCID 178452518, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 66982147HCID 66982147, compoundYield 127.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.25 mL, 3.24 mmol) was added to a solution of a TFA salt of tert-butyl (1R,3S,5R)-3-(5-(2-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-benzimidazol-6-yl)-6-quinoxalinyl)-1H-benzimidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (65 mg) in DCM (0.5 mL) and the mixture was stirred at rt for 16 h. The volatiles were removed and the residue was triturated with Et2O. The resulting solid was collected via filtration funnel and rinsed with Et2O to yield a TFA salt of 2,6-bis(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxaline (60 mg) as yellow solid. LC-MS retention time 1.51 min; m/z 525 [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 9.52 (1H, s), 8.58 (1H, s), 8.36 (1H, s), 8.22-8.33 (2H, m), 8.30 (1H, d, J=9.5 Hz), 8.08 (1H, s), 7.76-7.94 (2H, m), 7.83 (1H, d, J=9.5 Hz), 4.80-5.05 (2H, m), 3.45-3.61 (2H, m), 2.70-2.92 (2H, m), 2.50-2.67 (2H, m), 2.00-2.18 (2H, m), 1.26 (2H, br s), 1.04 (2H, br s).

Workup

  1. customThe volatiles were removed
  2. customthe residue was triturated with Et2O
  3. filtrationThe resulting solid was collected via filtration funnel
  4. washrinsed with Et2O

Sources & evidence

ORD record
ord-6dcb19269ae145eaa1c17ae712535ecd
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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