Sodium Sulfate → (+/-)-6-{[((1S,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]hept-6-yl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 2233005Notes

Reaction equation

HRID 2233005 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:20][C@H:19]3[C@H:16]([CH2:17][C@@H:18]3[NH2:21])[CH2:15]1)=[N:9][C:8]([O:22][CH3:23])=[CH:7][CH:6]=2.[O-]S([O-])(=O)=O.[Na+].[Na+].[O:31]=[C:32]1[CH2:37][S:36][C:35]2[CH:38]=[CH:39][C:40]([CH:42]=O)=[N:41][C:34]=2[NH:33]1.[BH4-].[Na+]>CCO.C(Cl)Cl>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:20][C@H:19]3[C@H:16]([CH2:17][C@@H:18]3[NH:21][CH2:42][C:40]3[CH:39]=[CH:38][C:35]4[S:36][CH2:37][C:32](=[O:31])[NH:33][C:34]=4[N:41]=3)[CH2:15]1)=[N:9][C:8]([O:22][CH3:23])=[CH:7][CH:6]=2

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 59295121HCID 59295121, compound

Product 1

HCID 11663263(+/-)-6-{[((1S,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]hept-6-yl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 35.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (±)-(1S,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]heptan-6-amine (31 mg, 0.098 mmol) in EtOH:DCM (1 mL, 1:1) were added Na2SO4 (21 mg, 0.15 mmol) followed by 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (19 mg, 0.097 mmol). After 12 h at 25° C., NaBH4 (6 mg, 0.15 mmol) was added. After an additional 1 hr, the reaction was concentrated and the residue was partitioned between DCM/H2O. The combined organic fractions were dried over MgSO4, concentrated and purified via column chromatography (silica, 0-3% MeOH in DCM (1% NH4OH)) yielding the title compound (17 mg, 35%) as a yellow oil: LC/MS (ES) m/e 495 (M+H)+; 1H NMR (CD3OD, 400 Hz) δ 8.62 (s, 1H), 8.20 (d, J=9.1 Hz, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.18 (d, J=9.1 Hz, 1H), 6.98 (d, J=7.9 Hz, 1H), 4.92 (s, 3H), 3.66-3.7 (m, 2H), 3.50-3.58 (m, 4H), 2.88-3.09 (m, 5H), 2.79-2.88 (m, 1H), 2.6-2.63 (m, 1H), 2.19-2.24 (m, 2H), 1.88-1.94 (m, 2H).

Workup

  1. waitAfter an additional 1 hr
  2. concentrationthe reaction was concentrated
  3. customthe residue was partitioned between DCM/H2O
  4. dry with materialThe combined organic fractions were dried over MgSO4
  5. concentrationconcentrated
  6. custompurified via column chromatography (silica, 0-3% MeOH in DCM (1% NH4OH))

Sources & evidence

ORD record
ord-e66e3c8e0fed469895b9ba3f07bcdb01
Source dataset
uspto-grants-2010_05
Patent number
US07709472B2

Reaction notes

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