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

HRID 734231Notes

Reaction equation

HRID 734231 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][CH:13]=3)[CH2:8][CH2:7]2)[CH2:4][C@H:3]1[OH:24].[O-]S([O-])(=O)=O.[Na+].[Na+].[O:32]=[C:33]1[CH2:38][S:37][C:36]2[CH:39]=[CH:40][C:41]([CH:43]=O)=[N:42][C:35]=2[NH:34]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCO>[OH:24][C@@H:3]1[CH2:4][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][CH:13]=3)[CH2:8][CH2:7]2)[CH2:6][C@@H:2]1[NH:1][CH2:43][C:41]1[CH:40]=[CH:39][C:36]2[S:37][CH2:38][C:33](=[O:32])[NH:34][C:35]=2[N:42]=1

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 57842930(2R,3S)-3-amino-8-[6-(methyloxy)-1,5-naphthyridin-4-yl]-8-azaspiro[4.5]decan-2-ol

Product 1

HCID 11504365(+/-)-6-[({(2S,3R)-3-hydroxy-8-[6-(methyloxy)-1,5-naphthyridin-4-yl]-8-azaspiro[4.5]dec-2-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 47%

Reagents, catalysts & solvents 1

HCID 21584144Dichloromethane ethanolSolvent

Procedure

To a solution of (2R,3S)-3-amino-8-[6-(methyloxy)-1,5-naphthyridin-4-yl]-8-azaspiro[4.5]decan-2-ol (40 mg, 0.122 mmol) in DCM-EtOH (1.5 mL, 1:1) at 25° C. were added Na2SO4 (35 mg, 0.244 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (24 mg, 0.122 mmol). After 12 h, NaBH(OAc)3 was added and after stirring an additional 2 h the solution was partitioned between NaHCO3 (sat)-DCM. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried (Na2SO4), concentrated and purified via column chromatography (silica, 2% MeOH in DCM (1% NH4OH)) yielding the title compound (29 mg, 47%) as a yellow foam: LCMS (ES) m/e 507 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=5.2 Hz, 1H), 8.17 (d, J=9.0 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.07 (d, J=9.0 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 6.83 (d, J=5.3 Hz, 1H), 4.12-4.19 (m, 1H), 4.03 (s, 3H), 3.92 (AB quart., 2H), 3.52-3.67 (m, 4H), 3.47 (s, 2H), 3.21-3.27 (m, 1H), 1.91-2.10 (m, 4H), 1.75-1.78 (m, 4H).

Workup

  1. customwas partitioned between NaHCO3 (sat)-DCM
  2. extractionThe aqueous phase was extracted several times with DCM
  3. dry with materialthe combined organic fractions were dried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified via column chromatography (silica, 2% MeOH in DCM (1% NH4OH))

Sources & evidence

ORD record
ord-796cc8e0645d4a5fa296b53de572277d
Source dataset
uspto-grants-2009_09
Patent number
US07592334B2

Reaction notes

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