Thionyl Chloride → HCID 90089466, compound

HRID 1775732Notes

Reaction equation

HRID 1775732 reaction equation
S(Cl)([Cl:3])=O.[F:5][C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[CH:8][C:7]=1[C@:13]12[CH2:22][O:21][C@@H:20]([CH2:23]O)[CH2:19][C@H:18]1[CH2:17][S:16][C:15]([NH:25][C:26](=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[N:14]2>C1(C)C=CC=CC=1>[Cl:3][CH2:23][C@@H:20]1[O:21][CH2:22][C@:13]2([C:7]3[CH:8]=[CH:9][C:10]([F:12])=[CH:11][C:6]=3[F:5])[N:14]=[C:15]([NH:25][C:26](=[O:33])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[S:16][CH2:17][C@@H:18]2[CH2:19]1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 86729527N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 90089466HCID 90089466, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Thionyl chloride (10.4 mL, 143 mmol) was added to a solution of N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (P1) (2.0 g, 4.8 mmol) in toluene (68 mL), and the reaction mixture was heated at 80° C. for 18 hours. After cooling to room temperature, it was concentrated in vacuo and azeotroped three times with dichloromethane. The residue was dissolved in dichloromethane, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Two purifications using silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) provided the product as an off-white solid. Yield: 1.88 g, 4.30 mmol, 90%. LCMS m/z 437.1 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.08-8.12 (m, 2H), 7.59-7.65 (m, 1H), 7.46-7.55 (m, 3H), 7.05-7.17 (m, 2H), 4.18 (dd, J=12.2, 1.3 Hz, 1H), 4.01 (d, J=12.3 Hz, 1H), 3.91-3.98 (m, 1H), 3.61-3.69 (m, 2H), 3.26-3.3 (m, 1H, assumed; partially obscured by solvent peak), 3.07 (br dd, J=13.3, 3.7 Hz, 1H), 2.91 (br dd, J=13.3, 2.5 Hz, 1H), 1.86-1.93 (m, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationit was concentrated in vacuo
  3. customazeotroped three times with dichloromethane
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washwashed with saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5e907df468644403bbfe29745efe102d
Source dataset
uspto-grants-2016_02
Patent number
US09260455B2

Reaction notes

Loading…