Hydrochloric Acid → 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-(t-butoxycarbonyl)-N-ethylamino)ethyloxyimino)quinazoline

HRID 220113Notes

Reaction equation

HRID 220113 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25](C=O)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.C(OC([CH2:37][CH2:38][NH:39][CH2:40][CH2:41][O:42][NH2:43])=O)(C)(C)C.Cl.[C:45](=[O:48])(O)[O-:46].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[CH2:26][C:25](=[N:43][O:42][CH2:41][CH2:40][N:39]([C:45]([O:46][C:10]([CH3:15])([CH3:11])[CH3:9])=[O:48])[CH2:38][CH3:37])[CH:24]=[CH:23][C:22]=3[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 577336564-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino) 6-formylquinazolineHCID 86630917N-(t-butoxycarbonyl)ethylaminoethoxyamine

Product 1

HCID 866309164-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-(t-butoxycarbonyl)-N-ethylamino)ethyloxyimino)quinazoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In tetrahydrofuran (1.5 ml) were dissolved 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline (IV-1, 120 mg) and N-(t-butoxycarbonyl)ethylaminoethoxyamine (110 mg), and 134 μl of 2 mol/L hydrochloric acid was added, then the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was poured into aqueous ice-cooled saturated sodium bicarbonate solution, and extracted with ethyl acetate. The organic layer was washed with water and aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The resulting residue was purified by amino column chromatography (eluting with hexane:ethyl acetate=1:1), and further re-purified by silica gel chromatography (eluting with hexane:ethyl acetate=1:1) to obtain 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-(t-butoxycarbonyl)-N-ethylamino)ethyloxyimino)quinazoline (V-16, 96 mg) as a yellow viscous oil.

Workup

  1. additionwas added
  2. customAfter completion of the reaction
  3. additionthe reaction mixture was poured into aqueous ice-
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water and aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe resulting residue was purified by amino column chromatography (eluting with hexane:ethyl acetate=1:1)
  9. customfurther re-purified by silica gel chromatography (eluting with hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-1149d957ec364d2f8f23cff88134330a
Source dataset
uspto-grants-2012_06
Patent number
US08202879B2

Reaction notes

Loading…