HCID 15976269, compound → HCID 11659485, compound

HRID 221539Notes

Reaction equation

HRID 221539 reaction equation
[F:1][C:2]([C@@H:5]1[N:10]2[C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([NH2:21])[C:12]=3[N:22]=[C:9]2[CH2:8][O:7][CH2:6]1)([CH3:4])[CH3:3]>FC(F)(F)C(O)=O.[Pt]=O>[F:1][C:2]([C@@H:5]1[N:10]2[C:11]3[C:20]4[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=4[N:14]=[C:13]([NH2:21])[C:12]=3[N:22]=[C:9]2[CH2:8][O:7][CH2:6]1)([CH3:3])[CH3:4]

Participants

4

Reactant 1

HCID 15976269HCID 15976269, compound

Product 1

HCID 11659485HCID 11659485, compoundYield 52.2%

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 6422Trifluoroacetic acidSolvent

Procedure

(11R)-11-(1-Fluoro-1-methylethyl)-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (300 mg, 1.00 mmol) was dissolved in 10 mL of trifluoroacetic acid and the solution was placed in a pressure bottle. Platinum oxide (227 mg) was then added and the reaction mixture was shaken under H2 at 50 PSI (3.4×105 Pa). After 20 hours, an additional 200 mg of catalyst was added and the mixture was shaken under H2 at 50 PSI (3.4×105 Pa) for an additional 24 h. The reaction mixture was filtered through a pad of CELITE filter agent. The pad was rinsed with a mixture of 2-propanol and CH2Cl2 and the combined filtrates were concentrated under reduced pressure to give a syrup. The syrup was partitioned between H2O and CHCl3. The aqueous portion was made basic by addition of 10% NaOH solution until the pH was higher than 12. The layers were separated and the organic portion was washed successively with 10% NaOH (2×), H2O and brine. The organic portion was then dried over Na2SO4, filtered and concentrated under reduced pressure to give a tan foam. Chromatography (SiO2, 25-33% CMA/CHCl3) followed by crystallization from ethyl acetate gave (11R)-11-(1-fluoro-1-methylethyl)-2,3,4,8,10,11-hexahydro-1H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (159 mg) as off-white crystals, mp 195.5-197.0° C.

Workup

  1. stirringthe mixture was shaken under H2 at 50 PSI (3.4×105 Pa) for an additional 24 h
  2. filtrationThe reaction mixture was filtered through a pad of CELITE
  3. filtrationfilter agent
  4. washThe pad was rinsed with a mixture of 2-propanol and CH2Cl2
  5. concentrationthe combined filtrates were concentrated under reduced pressure
  6. customto give a syrup
  7. customThe syrup was partitioned between H2O and CHCl3
  8. additionThe aqueous portion was made basic by addition of 10% NaOH solution until the pH
  9. customThe layers were separated
  10. washthe organic portion was washed successively with 10% NaOH (2×), H2O and brine
  11. dry with materialThe organic portion was then dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto give a tan foam
  15. customChromatography (SiO2, 25-33% CMA/CHCl3) followed by crystallization from ethyl acetate

Sources & evidence

ORD record
ord-b9ab1544e2d64093a8b4f5ee5317415e
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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