Sodium Sulfate → 6-{[(2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 1787689Notes

Reaction equation

HRID 1787689 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][NH2:20])[CH2:14][CH2:13]1)=[N:9][C:8]([O:21][CH3:22])=[CH:7][CH:6]=2.[O-]S([O-])(=O)=O.[Na+].[Na+].[O:30]=[C:31]1[CH2:36][S:35][C:34]2[CH:37]=[CH:38][C:39]([CH:41]=O)=[N:40][C:33]=2[NH:32]1.[BH4-].[Na+]>C(Cl)Cl.CCO>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][NH:20][CH2:41][C:39]3[CH:38]=[CH:37][C:34]4[S:35][CH2:36][C:31](=[O:30])[NH:32][C:33]=4[N:40]=3)[CH2:14][CH2:13]1)=[N:9][C:8]([O:21][CH3:22])=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 57599574(2-{4-[3-Fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)amine

Product 1

HCID 115259156-{[(2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 30%

Reagents, catalysts & solvents 1

HCID 21584144Dichloromethane ethanolSolvent

Procedure

To a solution of (2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)amine (155 mg, 0.508 mmol) in DCM-EtOH (5 mL, 1:1) were added Na2SO4 (144 mg, 1.02 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (99 mg, 0.508 mmol). After 12 h at 25° C., the imine was quenched by addition of NaBH4 (29 mg, 0.762 mmol) in one portion. After an additional 1 h, the solution was partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and the combined organic fractions were dried (Na2SO4), concentrated and purified by column chromatography (silica, 1% MeOH in DCM (1% NH4OH)) affording the title compound (73 mg, 30%) as a light yellow solid: LCMS (ES) m/e 484 (M+H)+; 1H NMR (CD3OD, 400 MHz) δ 8.46 (d, J=4.8 Hz, 1H), 8.11 (d, J=9.1 Hz, 1H), 7.74 (d, J=7.9 Hz, 1H), 7.13 (d, J=9.1 Hz, 1H), 7.07 (d, J=7.9 Hz, 1H), 4.06 (s, 3H), 3.92 (s, 2H), 3.83 (bs, 4H), 3.54 (bs, 2H), 2.88 (s, 2H), 2.66-2.72 (m, 6H).

Workup

  1. waitAfter an additional 1 h
  2. customthe solution was partitioned between H2O-DCM
  3. washThe aqueous phase was washed several times with DCM
  4. dry with materialthe combined organic fractions were dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by column chromatography (silica, 1% MeOH in DCM (1% NH4OH))

Sources & evidence

ORD record
ord-4e315c8f4e184aab9984a7f0ddb67c6f
Source dataset
uspto-grants-2009_03
Patent number
US07511035B2

Reaction notes

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