Sodium Sulfate → HCID 58846592, compound

HRID 1271705Notes

Reaction equation

HRID 1271705 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@@H:9]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[N:19]=3)[N:14]=[CH:13][CH:12]=2)[OH:10])[CH2:4][CH2:3]1.[O:23]=[C:24]1[NH:33][C:32]2[N:31]=[CH:30][C:29]([CH:34]=O)=[CH:28][C:27]=2[CH2:26][CH2:25]1.[O-]S([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>ClC(Cl)C.C(O)C>[OH:10][C@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[N:19]=2)[N:14]=[CH:13][CH:12]=1)[CH2:8][N:5]1[CH2:6][CH2:7][CH:2]([NH:1][CH2:34][C:29]2[CH:28]=[C:27]3[C:32](=[N:31][CH:30]=2)[NH:33][C:24](=[O:23])[CH2:25][CH2:26]3)[CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 4311764Sodium borohydrideHCID 18454515443956-57-8HCID 23400257HCID 23400257, compound

Product 1

HCID 58846592HCID 58846592, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of (R)-2-(4-aminopiperidin-1-yl)-1-(6-methoxy-[1,5]naphthyridin-4-yl)ethanol (2f) (0.34 g, 1.13 mmole) in dichloroethane (10 mL) and dry ethanol (5 mL) at RT was added 7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxaldehyde (113 g) (0.20 g, 1.13 mmole) and granular Na2SO4 (approximately 100 mg). After 72 h, the reaction was concentrated. The remaining residue was dissolved in dry ethanol and reacted with NaBH4 (0.043 g, 1.13 mmole). After 12 h at RT, the reaction was concentrated under vacuum and the residue was dissolved in a mixture of H2O (10 mL) and saturated aqueous NaHCO3 (50 mL). The aqueous solution was extracted with EtOAc (2×75 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 (0.11 g, 21%) as a white solid: 1H NMR (400 MHz, d6-DMSO) δ 10.43 (br s, 1H), 8.77 (d, J=4.5 Hz, 1H), 8.23 (d, J=9.0 Hz, 1H), 8.01 (s, 1H), 7.75 (d, J=4.5 Hz, 1H), 7.58 (s, 1H), 7.24 (d, J=9.0 Hz, 1H), 5.77 (m, 1H), 5.23 (br s, 1H), 4.02 (s, 3H), 3.63 (s, 2H), 3.38 (m, 2H), 3.11 (m, 1H), 2.83 (m, 2H), 2.65 (m, 1H), 2.47 (m, 2H), 2.32 (m, 1H), 2.17 (m, 1H), 1.79 (m, 2H), 1.27 (m, 2H); MS (ES) m/e 463 M+H)+.

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutionThe remaining residue was dissolved in dry ethanol
  3. waitAfter 12 h at RT
  4. concentrationthe reaction was concentrated under vacuum
  5. dissolutionthe residue was dissolved in a mixture of H2O (10 mL) and saturated aqueous NaHCO3 (50 mL)
  6. extractionThe aqueous solution was extracted with EtOAc (2×75 mL)
  7. washthe combined organic phases were washed with brine
  8. dry with materialthen were dried over Na2SO4

Sources & evidence

ORD record
ord-5e3ef9905c224588806fab61fa6f975c
Source dataset
uspto-grants-2007_04
Patent number
US07205408B2

Reaction notes

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