1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 73507167, compound

HRID 1775734Notes

Reaction equation

HRID 1775734 reaction equation
N12CCCN=C1CCCCC2.[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C@:20]12[CH2:29][O:28][C@@H:27]([CH3:30])[CH2:26][C@H:25]1[CH2:24][S:23][C:22]([NH:31]C(=O)C1C=CC=CC=1)=[N:21]2>CO>[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C@:20]12[CH2:29][O:28][C@@H:27]([CH3:30])[CH2:26][C@H:25]1[CH2:24][S:23][C:22]([NH2:31])=[N:21]2

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 90089467HCID 90089467, compound

Product 1

HCID 73507167HCID 73507167, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

1,8-Diazabicyclo[5.4.0]undec-7-ene (0.5 mL, 3 mmol) was added to a suspension of N-[(4aR,6S,8aS)-8a-(2,4-difluorophenyl)-6-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C22) (1.40 g, 3.48 mmol) in methanol (100 mL), and the resulting mixture was heated at 80° C. for 18 hours. After removal of solvent in vacuo, the residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate; the aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (Eluent: ethyl acetate) afforded the product as a white solid. Yield: 840 mg, 2.82 mmol, 81%. LCMS m/z 299.2 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 7.30-7.38 (m, 1H), 6.92-7.00 (m, 2H), 4.08 (dd, J=11.1, 2.2 Hz, 1H), 3.69-3.78 (m, 1H), 3.65 (d, J=11.1 Hz, 1H), 2.83-2.93 (m, 2H), 2.62-2.68 (m, 1H), 1.65-1.76 (m, 1H), 1.54 (ddd, J=13.1, 4.1, 2.4 Hz, 1H), 1.22 (d, J=6.2 Hz, 3H).

Workup

  1. customAfter removal of solvent in vacuo
  2. customthe residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification via silica gel chromatography (Eluent: ethyl acetate)

Sources & evidence

ORD record
ord-0e363319db33400199e96e905f2eb916
Source dataset
uspto-grants-2016_02
Patent number
US09260455B2

Reaction notes

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