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

HRID 625593Notes

Reaction equation

HRID 625593 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[N:31]=[C:32]5[C:37](=[CH:38][CH:39]=4)[N:36]=[C:35]([C:40]4[CH:61]=[CH:60][C:43]6[NH:44][C:45]([C@@H:47]7[CH2:52][C@@H:51]8[C@@H:49]([CH2:50]8)[N:48]7C(OC(C)(C)C)=O)=[N:46][C:42]=6[CH:41]=4)[CH:34]=[CH: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:39]=[CH: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)[N: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 178452517HCID 178452517, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 669818382,6-bis(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)-1,5-naphthyridineYield 78.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.25 mL, 3.2 mmol) was added to a solution of tert-butyl (1R,3S,5R)-3-(5-(6-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-b enzimidazol-6-yl)-1,5-naphthyridin-2-yl)-1H-benzimidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (20 mg, 0.028 mmol) in DCM (0.5 mL) and the mixture was stirred at rt for 16 h. The volatile were removed under vacuum and the residue was triturated with Et2O. The resulting solid was collected via filtration 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)-1,5-naphthyridine (26 mg, 0.022 mmol, 78% yield) as a yellow solid. LC-MS retention time 1.41 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 8.61 (2H, d, J=8.8 Hz), 8.51 (2H, s), 8.40 (2H, d, J=9.0 Hz), 8.23 (2H, dd, J=8.5, 1.5 Hz), 7.81 (2H, d, J=8.5 Hz), 4.74-4.97 (2H, m), 3.47-3.57 (2H, m), 2.78-2.88 (2H, m), 2.52-2.65 (2H, m), 2.04-2.15 (2H, m), 1.22-1.33 (2H, m), 0.99-1.11 (2H, m).

Workup

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

Sources & evidence

ORD record
ord-be950b59a8e445aeb969a034d64c3f23
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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