HCID 86659022, compound → HCID 178452528, compound

HRID 1471170Notes

Reaction equation

HRID 1471170 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]2[NH:15][C:16]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[CH:25]=[C:24]([C:29]3[CH:34]=[CH:33][C:32]([C:35]5[NH:39][C:38]([CH:40]6[CH2:45][C@@H:44]7[C@@H:42]([CH2:43]7)[N:41]6C(OCC6C=CC=CC=6)=O)=[N:37][CH:36]=5)=[CH:31][CH:30]=3)[CH:23]=[CH:22]4)=[CH:17][N:18]=2)[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C@@H:42]12[CH2:43][C@@H:44]1[CH2:45][C@@H:40]([C:38]1[NH:37][CH:36]=[C:35]([C:32]3[CH:33]=[CH:34][C:29]([C:24]4[CH:25]=[C:26]5[C:21](=[CH:22][CH:23]=4)[CH:20]=[C:19]([C:16]4[NH:15][C:14]([C@@H:13]6[CH2:12][C@@H:11]7[C@@H:9]([CH2:10]7)[N:8]6[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:18][CH:17]=4)[CH:28]=[CH:27]5)=[CH:30][CH:31]=3)[N:39]=1)[NH:41]2

Participants

4

Reactant 1

HCID 86659022HCID 86659022, compound

Product 1

HCID 178452528HCID 178452528, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A reaction mixture of (1R,5R)-benzyl 3-(5-(4-(6-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (0.305 g, 0.416 mmol) and NaHCO2 (0.070 g, 0.832 mmol) in MeOH (15 mL) was charged with 10% Pd/C (0.022 g, 0.021 mmol). The resulting suspension was vacuum flushed with N2 (3×) and placed under 1 atm of H2 (balloon) for 3 h at room temperature. The mixture was then filtered though a pad of diatomaceous earth (CELITE®) and concentrated under vacuum. An off-white solid corresponding to (1R,3S,5R)-tert-butyl 3-(5-(6-(4-(2-((1R,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (0.235 g) was recovered and used without further purification. LC/MS [M+H]+=599; Rt=1.96 min is product. Column Luna 3u C18 2×50 mm; start % B: 0, final % B: 100 Solvent A: 10% Acetonitrile/90% H2O+1% TFA; Solvent B: 90% Acetonitrile/10% H2O+1% TFA; flow rate 4 ml/min. Run time: 5 min. Purity=94%. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.00 (2 H, br. s.), 8.11-8.32 (3 H, m), 7.88-8.02 (5 H, m), 7.72-7.88 (9 H, m), 7.63 (4 H, br. s.), 4.64 (2 H, br. s.), 4.42 (1 H, t, J=7.93 Hz), 3.97-4.18 (1 H, m), 3.45 (1 H, br. s.), 3.17 (3 H, s), 2.96 (1 H, dd, J=13.43, 6.71 Hz), 2.08-2.43 (6 H, m), 1.66 (2 H, br. s.), 1.07-1.50 (20 H, m), 0.81-0.89 (3 H, m), 0.77 (1 H, br. s.), 0.45-0.61 (3 H, m), 0.30 (1 H, br. s.).

Workup

  1. customflushed with N2 (3×)
  2. filtrationThe mixture was then filtered though a pad of diatomaceous earth (CELITE®)
  3. concentrationconcentrated under vacuum
  4. customAn off-white solid corresponding to (1R,3S,5R)-tert-butyl 3-(5-(6-(4-(2-((1R,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (0.235 g) was recovered
  5. customused without further purification
  6. custom5 min

Sources & evidence

ORD record
ord-f1c0e6051edf4a60b354add4c20ba3a9
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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