Triethylamine → (2E)-3-[(11S)-6-amino-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-3-yl]-N,N-dimethylprop-2-enamide

HRID 221630Notes

Reaction equation

HRID 221630 reaction equation
[C:1]1([CH3:22])C=CC=C[C:2]=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH2:23]([N:25]([CH2:28]C)CC)C.Br[C:31]1[CH:40]=[C:39]2[C:34]([C:35]3[N:44]4[C@@H:45]([CH3:49])[CH2:46][O:47][CH2:48][C:43]4=[N:42][C:36]=3[C:37]([NH2:41])=[N:38]2)=[CH:33][CH:32]=1.C([O-])([O-])=[O:51].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.C(Cl)Cl>[NH2:41][C:37]1[C:36]2[N:42]=[C:43]3[CH2:48][O:47][CH2:46][C@H:45]([CH3:49])[N:44]3[C:35]=2[C:34]2[C:39](=[CH:40][C:31](/[CH:2]=[CH:1]/[C:22]([N:25]([CH3:28])[CH3:23])=[O:51])=[CH:32][CH:33]=2)[N:38]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 58406168(11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amine

Product 1

HCID 67156540(2E)-3-[(11S)-6-amino-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-3-yl]-N,N-dimethylprop-2-enamide

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A scintillation vial was charged with palladium acetate (22 mg, 0.10 mmol), tri-o-tolylphosphine (61 mg, 0.20 mmol), anhydrous DMF (1.0 mL) and triethylamine (0.4 mL, 3.0 mmol). The orange homogeneous solution was then added to a solution of (11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (333 mg, 1.00 mmol) dissolved in 10 mL of anhydrous DMF followed by the addition of a solution of N,N-dimethylacrlylamide (120 mg, 1.20 mmol) dissolved in 1.0 mL of anhydrous DMF. The mixture was transferred to a glass vessel and the vessel was purged with N2, sealed and heated to 120° C. for 18 hours. The reaction mixture was cooled and concentrated to dryness under reduced pressure to give a golden solid. The solid was treated with CH2Cl2 and saturated aqueous K2CO3 solution and the layers were separated. The organic layer was concentrated to dryness to give a light-brown solid. Chromatography (SiO2, 0-15% CMA/CHCl3) gave a white solid that was crystallized from acetonitrile to give 210 mg of the (2E)-3-[(11S)-6-amino-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-3-yl]-N,N-dimethylprop-2-enamide as off-white crystals, mp>250° C.

Workup

  1. additionfollowed by the addition of a solution of N,N-dimethylacrlylamide (120 mg, 1.20 mmol)
  2. customThe mixture was transferred to a glass vessel
  3. customthe vessel was purged with N2
  4. customsealed
  5. temperatureThe reaction mixture was cooled
  6. concentrationconcentrated to dryness under reduced pressure
  7. customto give a golden solid
  8. customthe layers were separated
  9. concentrationThe organic layer was concentrated to dryness
  10. customto give a light-brown solid
  11. customthat was crystallized from acetonitrile

Sources & evidence

ORD record
ord-bf59fe089e5e4e4d8af0287a23437d60
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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