Pyridine → HCID 89573878, compound

HRID 1911014Notes

Reaction equation

HRID 1911014 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C@@:11]3([CH3:25])[N:12]=[C:13]([NH:16]C(=O)C4C=CC=CC=4)[S:14][CH2:15][C@H:10]3[CH2:9][O:8][C:6]=2[CH:7]=1.N1C=CC=CC=1.CO[NH3+].[Cl-]>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C@@:11]3([CH3:25])[N:12]=[C:13]([NH2:16])[S:14][CH2:15][C@H:10]3[CH2:9][O:8][C:6]=2[CH:7]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 11639O-methylhydroxylammonium chlorideHCID 89573556HCID 89573556, compound

Product 1

HCID 89573878HCID 89573878, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of rel-N-((4aR,10bS)-8-Fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-yl)benzamide from step F5 (1.27 g, 3.56 mmol), pyridine (1.0 mL, 12.36 mmol), and hydroxylamine methyl ether hydrochloride (1.0 g, 12.0 mmol) in ethanol (100 mL) was heated at 50° C. for 24 h. The mixture was concentrated under reduced pressure. The residue was diluted with saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using silica gel column chromatography (5-10% MeOH/dichloromethane) to afford rel-(4aR,10bS)-8-fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-amine (644 mg, 2.50 mmol, 70% yield) as a viscous yellow oil. LCMS (M+H)+=253.1. 1H NMR (500 MHz, chloroform-d) δ 7.59 (dd, J=8.8, 6.6 Hz, 1H), 6.73-6.65 (m, 1H), 6.51 (dd, J=10.1, 2.6 Hz, 1H), 4.40 (dd, J=11.4, 2.8 Hz, 1H), 4.21 (dd, J=11.4, 5.7 Hz, 1H), 3.15-3.02 (m, 2H), 2.14 (dddd, J=8.4, 5.7, 3.7, 2.9 Hz, 1H), 1.60 (s, 3H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionThe residue was diluted with saturated aqueous sodium bicarbonate solution
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified

Sources & evidence

ORD record
ord-08d815c05eb64e6f8b82dfda0c9db0bb
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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