Sodium Sulfate → (+/-)-6-[({(2S,3R)-8-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxy-8-azaspiro[4.5]dec-2-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 734234Notes

Reaction equation

HRID 734234 reaction equation
[NH2:1][C@H:2]1[CH2:6][C:5]2([CH2:11][CH2:10][N:9]([C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[N:20]=4)[N:15]=[CH:14][C:13]=3[F:24])[CH2:8][CH2:7]2)[CH2:4][C@H:3]1[OH:25].[O-]S([O-])(=O)=O.[Na+].[Na+].[O:33]=[C:34]1[CH2:39][S:38][C:37]2[CH:40]=[CH:41][C:42]([CH:44]=O)=[N:43][C:36]=2[NH:35]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCO>[F:24][C:13]1[CH:14]=[N:15][C:16]2[C:21]([C:12]=1[N:9]1[CH2:10][CH2:11][C:5]3([CH2:6][C@H:2]([NH:1][CH2:44][C:42]4[CH:41]=[CH:40][C:37]5[S:38][CH2:39][C:34](=[O:33])[NH:35][C:36]=5[N:43]=4)[C@H:3]([OH:25])[CH2:4]3)[CH2:7][CH2:8]1)=[N:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 57842929(2R,3S)-3-amino-8-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-8-azaspiro[4.5]decan-2-ol

Product 1

HCID 11591762(+/-)-6-[({(2S,3R)-8-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxy-8-azaspiro[4.5]dec-2-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 84%

Reagents, catalysts & solvents 1

HCID 21584144Dichloromethane ethanolSolvent

Procedure

To a solution of (2R,3S)-3-amino-8-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-8-azaspiro[4.5]decan-2-ol (0.26 mg, 75.1 μmol) in DCM-EtOH (1 mL, 1:1) were added Na2SO4 (16 mg, 0.112 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (15 mg, 75.1 μmol). After 12 h at 25° C., the imine was quenched by addition of NaBH(OAc)3 (32 mg, 0.150 mmol) in one portion. After an additional 1 h, the solution was partitioned between NaHCO3-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 (33 mg, 84%) as a light yellow oil: LCMS (ES) m/e 525 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=5.5 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.01 (d, J=9.0 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 4.12-4.19 (m, 1H), 4.03 (s, 3H), 3.92 (AB quart., 2H), 3.52-3.67 (m, 4H), 3.46 (s, 2H), 3.00-3.21 (m, 1H), 1.94-1.96 (m, 1H), 1.79-1.91 (m, 1H), 1.65-1.71 (m, 4H).

Workup

  1. waitAfter an additional 1 h
  2. customthe solution was partitioned between NaHCO3-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-da6b5768033f450b8c3e464e8d93a8ae
Source dataset
uspto-grants-2009_09
Patent number
US07592334B2

Reaction notes

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