Hydrochloric Acid → (αR)-6-Methoxy-α-[[4-[[(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)methyl]amino]-1-piperidinyl]methyl]-4-quinolinemethanol

HRID 1271693Notes

Reaction equation

HRID 1271693 reaction equation
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][C@@H:10]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][CH:13]=2)[OH:11])[CH2:5][CH2:4]1.[N:24]1[C:33]2[NH:32][CH2:31][CH2:30][CH2:29][C:28]=2[CH:27]=[CH:26][C:25]=1[CH:34]=O.C(N(CC)CC)C.[O-]S([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>C(Cl)Cl.C(O)C>[CH3:23][O:22][C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][CH:13]=[C:12]2[C@@H:10]([OH:11])[CH2:9][N:6]1[CH2:7][CH2:8][CH:3]([NH:2][CH2:34][C:25]2[CH:26]=[CH:27][C:28]3[CH2:29][CH2:30][CH2:31][NH:32][C:33]=3[N:24]=2)[CH2:4][CH2:5]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 24436Sodium SulfateHCID 4311764Sodium borohydrideHCID 11312661HCID 11312661, compoundHCID 218737255,6,7,8-Tetrahydro-1,8-naphthyridine-2-carbaldehyde

Product 1

HCID 10204096(αR)-6-Methoxy-α-[[4-[[(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)methyl]amino]-1-piperidinyl]methyl]-4-quinolinemethanolYield 69%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the mono hydrochloride salt of (R)-2-(4-aminopiperidin-1-yl)-1-(6-methoxyquinolin-4-yl) ethanol (1d) (0.34 g, 1.0 mmole) in CH2Cl2 (25 mL) and dry ethanol (10 mL) at RT was added 5,6,7,8-tetrahydro[1,8]naphthyridine-2-carboxaldehyde (prepared according to the procedure of WO 98/08840, 0.17 g, 1.0 mmole), triethylamine (0.10 g, 1.0 mmole), and granular Na2SO4 (approximately 200 mg). After 36 h, the reaction was filtered through a sintered-glass funnel and the filtrate was concentrated. The remaining residue was dissolved in dry ethanol and reacted with NaBH4 (0.04 g, 1.0 mmole). After 12 h at RT, the reaction was concentrated under vacuum and the residue was dissolved in a mixture of H2O (2 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous solution was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine then were dried over Na2SO4. Flash chromatography on silica gel (9:1 CHCl3/MeOH containing 5% NH4OH) afforded the title compound (0.31 g, 69%) as a white solid:

Workup

  1. customprepared
  2. filtrationthe reaction was filtered through a sintered-glass funnel
  3. concentrationthe filtrate was concentrated
  4. dissolutionThe remaining residue was dissolved in dry ethanol
  5. waitAfter 12 h at RT
  6. concentrationthe reaction was concentrated under vacuum
  7. dissolutionthe residue was dissolved in a mixture of H2O (2 mL) and saturated aqueous NaHCO3 (10 mL)
  8. extractionThe aqueous solution was extracted with EtOAc (2×50 mL)
  9. washthe combined organic phases were washed with brine
  10. dry with materialthen were dried over Na2SO4

Sources & evidence

ORD record
ord-0dd36d99dfe24c749b11b4b2e4998759
Source dataset
uspto-grants-2007_04
Patent number
US07205408B2

Reaction notes

Loading…