Ethoxyacetyl chloride → 1-{[3-Amino-6-(benzyloxy)quinolin-4-yl]amino}-2-methylpropan-2-ol

HRID 2383152Notes

Reaction equation

HRID 2383152 reaction equation
C(OC1C=C2C(=CC=1)N=CC([N+]([O-])=O)=C2[Cl:22])C1C=CC=CC=1.C(OC1C=C2C(C(Cl)=C([N+]([O-])=O)C=N2)=CC=1)C1C=CC=CC=1.[CH2:45]([O:47][CH2:48][C:49](Cl)=[O:50])[CH3:46].[NH2:52][C:53]1[CH:54]=[N:55][C:56]2[C:61]([C:62]=1[NH:63][CH2:64][C:65]([CH3:68])([OH:67])[CH3:66])=[CH:60][C:59]([O:69][CH2:70][C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)=[CH:58][CH:57]=2>C(#N)C>[NH2:52][C:53]1[CH:54]=[N:55][C:56]2[C:61]([C:62]=1[NH:63][CH2:64][C:65]([CH3:66])([OH:67])[CH3:68])=[CH:60][C:59]([O:69][CH2:70][C:71]1[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=1)=[CH:58][CH:57]=2.[ClH:22].[CH2:70]([O:69][C:59]1[CH:60]=[C:61]2[C:56](=[CH:57][CH:58]=1)[N:55]=[CH:54][C:53]([NH:52][C:49](=[O:50])[CH2:48][O:47][CH2:45][CH3:46])=[C:62]2[NH:63][CH2:64][C:65]([OH:67])([CH3:66])[CH3:68])[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1

Participants

7

Reactant 4

HCID 84189Ethoxyacetyl chlorideHCID 210757517-(Benzyloxy)-4-chloro-3-nitroquinolineHCID 670509451-{[3-Amino-6-(benzyloxy)quinolin-4-yl]amino}-2-methylpropan-2-olHCID 670509926-(Benzyloxy)-4-chloro-3-nitroquinoline

Product 2

HCID 670509451-{[3-Amino-6-(benzyloxy)quinolin-4-yl]amino}-2-methylpropan-2-olHCID 67051090N-{6-benzyloxy-4-[(2-hydroxy-2-methylpropyl)amino]quinolin-3-yl}-2-ethoxyacetamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-{[3-Amino-6-(benzyloxy)quinolin-4-yl]amino}-2-methylpropan-2-ol was prepared according to the general methods described in Parts A and B of Example 54 using 6-benzyloxy-4-chloro-3-nitroquinoline in lieu of 7-benzyloxy-4-chloro-3-nitroquinoline in Part A. Ethoxyacetyl chloride (5.37 g, 43.8 mmol) was added to a solution of 1-{[3-amino-6-(benzyloxy)quinoline-4-yl]amino}-2-methylpropan-2-ol (7.45 g, 22.1 mmol) in acetonitrile (230 mL), and the reaction was stirred overnight. The solvent was removed under reduced pressure, and the residue was dissolved in dichloromethane. The resulting solution was washed with aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on a HORIZON HPFC system (an automated, modular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va., USA) (silica gel cartridge, eluting with dichloromethane:methanol ranging in ratios from 98:2 to 95:5) to provide N-{6-benzyloxy-4-[(2-hydroxy-2-methylpropyl)amino]quinolin-3-yl}-2-ethoxyacetamide hydrochloride.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washThe resulting solution was washed with aqueous sodium bicarbonate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on a HORIZON HPFC system (
  8. custommodular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va
  9. wash, USA) (silica gel cartridge, eluting with dichloromethane:methanol ranging in ratios from 98:2 to 95:5)

Sources & evidence

ORD record
ord-3cf8d755e037415880daff93072d7c5a
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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