Sodium Sulfate → 1-[2-((2S)-2-{[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}-4-morpholinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one

HRID 657064Notes

Reaction equation

HRID 657064 reaction equation
[NH2:1][CH2:2][C@@H:3]1[O:8][CH2:7][CH2:6][N:5]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:23])[CH2:4]1.[O:24]1[C:33]2[CH:32]=[C:31]([CH:34]=O)[N:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25]1.S([O-])([O-])(=O)=O.[Na+].[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.C(Cl)Cl>[O:24]1[C:33]2[CH:32]=[C:31]([CH2:34][NH:1][CH2:2][C@@H:3]3[O:8][CH2:7][CH2:6][N:5]([CH2:9][CH2:10][N:11]4[C:20]5[C:15](=[N:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=5)[CH:14]=[CH:13][C:12]4=[O:23])[CH2:4]3)[N:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 689928521-{2-[(2S)-2-(Aminomethyl)-4-morpholinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one

Product 1

HCID 250325441-[2-((2S)-2-{[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}-4-morpholinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-oneYield 33%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 1-{2-[(2S)-2-(aminomethyl)-4-morpholinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one (0.100 g, 0.314 mmol) in 1:1 (MeOH/CH2Cl2) (25 mL) were added 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde) (for a synthesis see WO2004/058144 Example 2(c) or WO03/087098, Example 19(d)) (0.052 g, 0.314 mmol) and sodium sulphate (0.100 g) and the resulting solution stirred for 18 hours at ambient temperature. Na(OAc)3BH (0.200 g, 0.942 mmol) was added and the solution stirred an additional 2 h. The reaction mixture was concentrated onto silica gel and chromatographed to yield a colorless oil and further purified by HPLC(CH3CN/H2O) to yield the title compound as a white powder (0.049 g, 33%).

Workup

  1. stirringthe solution stirred an additional 2 h
  2. concentrationThe reaction mixture was concentrated onto silica gel
  3. customchromatographed
  4. customto yield a colorless oil
  5. customfurther purified by HPLC(CH3CN/H2O)

Sources & evidence

ORD record
ord-ae9934327a094ea099147afd1d7b9cb7
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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