1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 68173769, compound

HRID 707686Notes

Reaction equation

HRID 707686 reaction equation
[F:1][CH:2]([F:29])[C@@H:3]1[C@@H:11]2[C@@:6]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:22]=3[F:28])([N:7]=[C:8]([NH:12]C(=O)C3C=CC=CC=3)[S:9][CH2:10]2)[CH2:5][O:4]1.N12CCCN=C1CCCCC2>CO>[F:29][CH:2]([F:1])[C@@H:3]1[C@@H:11]2[C@@:6]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:22]=3[F:28])([N:7]=[C:8]([NH2:12])[S:9][CH2:10]2)[CH2:5][O:4]1

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 68173771HCID 68173771, compound

Product 1

HCID 68173769HCID 68173769, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

N-((4aS,5S,7aS)-5-(difluoromethyl)-7a-(2,3-difluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide, obtained in Preparation Example 1-(8), (891 mg) was dissolved in methanol (10 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (1.02 g) was added, and the solution was heated to reflux (heating block temperature 70° C.). After 16 h, the reaction mixture was cooled, concentrated under reduced pressure, and the residue purified by silica gel column chromatography (0% to 80% EtOAc in hexanes) to afford the title compound (565 mg). 1H NMR (400 MHz, CDCl3) δ ppm 2.88 (dd, J=13.4, 4.0 Hz, 1H), 3.13 (dd, J=13.6, 3.3 Hz, 1H), 3.24 (dt, J=7.7, 3.7 Hz, 1H), 3.89 (d, J=8.3 Hz, 1H), 4.33-4.70 (m, 4H), 5.94 (td, J=56.3, 3.8 Hz, 1H), 7.05-7.25 (m, 3H)

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux
  3. temperaturethe reaction mixture was cooled
  4. concentrationconcentrated under reduced pressure
  5. customthe residue purified by silica gel column chromatography (0% to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-88ef38e126144e84951dacdbf8fb2e1d
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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