Chloroform → (11R)-2-(benzyloxy)-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amine

HRID 221551Notes

Reaction equation

HRID 221551 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N+:15]([O-])=[CH:14][C:13]1[N:20]=[C:21]3[CH2:26][O:25][CH2:24][C@H:23]([CH3:27])[N:22]3[C:12]2=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(Cl)(Cl)C([N:32]=C=O)=O.C(Cl)(Cl)Cl>ClCCl>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[C:14]([NH2:32])[C:13]1[N:20]=[C:21]3[CH2:26][O:25][CH2:24][C@@H:23]([CH3:27])[N:22]3[C:12]2=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6212ChloroformHCID 76400Trichloroacetyl isocyanateHCID 67157212(11S)-2-(Benzyloxy)-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline 5-oxide

Product 1

HCID 67156348(11R)-2-(benzyloxy)-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amineYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(11S)-2-(Benzyloxy)-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline 5-oxide (2.02 g, 5.59 mmol) and trichloroacetyl isocyanate (0.87 mL, 7.27 mmol) were dissolved in dichloromethane (50 mL) under an atmosphere of N2. After one hour, the reaction was quenched with a small amount of methanol, and the solvent was removed under reduced pressure. The resulting residue was suspended in methanol (50 mL) and treated with NaOMe (25% in MeOH, 8 mL) for 20 hours. The volatiles were removed under reduced pressure and the residue was partitioned between dichloromethane and water, adjusting to pH 11 with NH4OH. The aqueous layer was extracted with dichloromethane (3×). The combined organic layers were then washed with brine and dried over Na2SO4, filtered, and concentrated to give a light-brown foam. Chromatography (SiO2, 0-20% CMA/CHCl3) gave (11R)-2-(benzyloxy)-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (1.35 g) as an off white solid, mp 100-120° C.

Workup

  1. customthe reaction was quenched with a small amount of methanol
  2. customthe solvent was removed under reduced pressure
  3. additiontreated with NaOMe (25% in MeOH, 8 mL) for 20 hours
  4. customThe volatiles were removed under reduced pressure
  5. customthe residue was partitioned between dichloromethane and water
  6. extractionThe aqueous layer was extracted with dichloromethane (3×)
  7. washThe combined organic layers were then washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a light-brown foam

Sources & evidence

ORD record
ord-e4639af426024660a918b4d58ea27b39
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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