Sodium Sulfate → 7-Chloro-6-({[((3S)-1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-3-piperidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 657068Notes

Reaction equation

HRID 657068 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:8][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.[Cl:24][C:25]1[C:34]([CH:35]=O)=[N:33][C:32]2[NH:31][C:30](=[O:37])[CH2:29][O:28][C:27]=2[CH:26]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.C(Cl)Cl>[Cl:24][C:25]1[C:34]([CH2:35][NH:1][CH2:2][C@@H:3]2[CH2:8][CH2:7][CH2:6][N:5]([CH2:9][CH2:10][N:11]3[C:20]4[C:15](=[N:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=4)[CH:14]=[CH:13][C:12]3=[O:23])[CH2:4]2)=[N:33][C:32]2[NH:31][C:30](=[O:37])[CH2:29][O:28][C:27]=2[CH:26]=1

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 574868727-Chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 68995687HCID 68995687, compound

Product 1

HCID 250325457-Chloro-6-({[((3S)-1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-3-piperidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 17%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 1-{2-[(3S)-3-(Aminomethyl)-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one (0.149 g, 0.472 mmol) in 1:1 (MeOH/CH2Cl2) (25 mL) were added 7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde (for a synthesis see WO2003064421, Example 15(c)) (0.100 g, 0.472 mmol) and sodium sulphate (0.100 g) and the resulting solution stirred for 18 hours at ambient temperature. Na(OAc)3BH (0.300 g, 1.42 mmol) was added and the solution stirred an additional 2 h. The reaction mixture was concentrated onto silica gel and chromatographed on a silica gel column [0-100% CHCl3/(90:10:1) CHCl3/MeOH/NH4OH)] to yield a colorless oil and then further purified by HPLC(CH3CN/H2O) to yield the title compound as a white powder (0.041 g, 17%).

Workup

  1. stirringthe solution stirred an additional 2 h
  2. concentrationThe reaction mixture was concentrated onto silica gel
  3. customchromatographed on a silica gel column [0-100% CHCl3/(90:10:1) CHCl3/MeOH/NH4OH)]
  4. customto yield a colorless oil
  5. customfurther purified by HPLC(CH3CN/H2O)

Sources & evidence

ORD record
ord-db7b0fe3e9214c16b773a9141c672c50
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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