Pyridine → HCID 89573556, compound

HRID 1911013Notes

Reaction equation

HRID 1911013 reaction equation
N1C=CC=CC=1.[F:7][C:8]1[CH:17]=[C:16]2[C:11]([C@:12]([NH:21][C:22]([NH:24][C:25](=[O:32])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[S:23])([CH3:20])[C@@H:13]([CH2:18]O)[CH2:14][O:15]2)=[CH:10][CH:9]=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.C(Cl)Cl>[F:7][C:8]1[CH:9]=[CH:10][C:11]2[C@@:12]3([CH3:20])[N:21]=[C:22]([NH:24][C:25](=[O:32])[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[S:23][CH2:18][C@H:13]3[CH2:14][O:15][C:16]=2[CH:17]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 89573589HCID 89573589, compound

Product 1

HCID 89573556HCID 89573556, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

DCM (40 mL) and pyridine (0.539 mL, 6.67 mmol) were added to rel-N-(((3S,4S)-7-fluoro-3-(hydroxymethyl)-4-methylchroman-4-yl)carbamothioyl)benzamide from step F4 (832 mg, 2.22 mmol), under an atmosphere of dry nitrogen. The mixture was cooled to −78° C. Triflic anhydride (0.751 mL, 4.44 mmol) was slowly added to the reaction solution over 10 min. The resulting mixture was stirred for 15 min and then further stirred for 1 h while warming to 0° C. After adding ethyl acetate, a saturated solution of sodium bicarbonate was added. The mixture was extracted with ethyl acetate, the combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was dissolved in dichloromethane and one drop of water and one drop of TFA was added. The reaction was stirred for 15 min, then concentrated in vacuo to afford rel-N-((4aR,10bS)-8-fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-yl)benzamide. The crude product was used for subsequent chemistry without further purification. LCMS (M+H)+=357.2.

Workup

  1. stirringfurther stirred for 1 h
  2. temperaturewhile warming to 0° C
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude product was dissolved in dichloromethane
  9. additionone drop of water and one drop of TFA was added
  10. stirringThe reaction was stirred for 15 min
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d609cf9c48a34d2998c6fc768c3c6a93
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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