HCID 59371579, compound → HCID 59371376, compound

HRID 2095399Notes

Reaction equation

HRID 2095399 reaction equation
C([O:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3C(OC(C)(C)C)=O)[CH:22]=2)[CH2:13]1)C1C=CC=CC=1>[Pd].CO.C(Cl)(Cl)Cl>[NH:26]1[CH2:27][CH2:28][CH2:29][C@H:25]1[CH2:24][O:23][C:21]1[CH:22]=[C:17]([N:14]2[CH2:15][CH2:16][C@H:12]([CH2:11][CH2:10][CH2:9][OH:8])[CH2:13]2)[CH:18]=[N:19][CH:20]=1

Participants

4

Reactant 1

HCID 59371579HCID 59371579, compound

Product 1

HCID 59371376HCID 59371376, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
70 °C

Procedure

In a 100 mL round-bottom flask with reflux condenser, 10% palladium on carbon (100 mg) was added to a solution of 3-[3(R)-[3-(benzyloxy)propyl]-1-pyrrolidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (500 mg, 1.01 mmol) in a mixed solvent of methanol/CHCl3 (40/5 mL). The reaction mixture was deoxygenated under vacuum, then H2 was admitted from a balloon placed above the condenser. The process was repeated three times, and the reaction mixture was stirred for 16 h at 70° C. in an oil bath. After cooling, the mixture was filtered through celite, and the filtrate was evaporated under reduced pressure. The crude product (340 mg) was purified by preparative HPLC (column: SunFire Prep C18, 100×19 mm, 5 μm particle size; UV detection at 220 nm; flow 20 mL/min; mobile phase: A, water with 0.05% CF3COOH; B, CH3OH; 15 to 100% B in A within 7 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3OH. The residue was basified with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried. After concentration in vacuo, the free base (250 mg, 81%) was obtained as a light-yellow oil. 1H NMR (CD3OD, 300 MHz) δ 7.54 (s, 1H), 7.50 (s, 1H), 6.53 (s, 1H), 4.10-4.04 (m, 1H), 3.99-3.97 (m, 1H), 3.61 (t, 2H, J=6.0 Hz), 3.53-3.50 (m, 2H), 3.35-3.30 (m, 1H), 3.00-2.94 (m, 3H), 2.38-2.18 (m, 2H), 2.09-1.95 (m, 2H), 1.91-1.81 (m, 2H), 1.71-1.51 (m, 6H). LC-MS (ESI) m/z 306 (M+H+).

Workup

  1. temperatureIn a 100 mL round-bottom flask with reflux condenser
  2. customThe reaction mixture was deoxygenated under vacuum
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered through celite
  5. customthe filtrate was evaporated under reduced pressure
  6. customThe crude product (340 mg) was purified by preparative HPLC (column
  7. wait15 to 100% B in A within 7 min)
  8. customThe eluate was partially evaporated under reduced pressure (bath 30° C.)
  9. customto remove CH3OH
  10. extractionextracted with EtOAc
  11. washThe combined organic layers were washed with brine
  12. customdried
  13. concentrationAfter concentration in vacuo

Sources & evidence

ORD record
ord-6a7f1cf85c8447559eff6920a9fc8fc4
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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