Sodium hydride → 7-Chloro-4-oxo-1-phenyl-3-(quinazolin-4-ylaminomethyl)-1,4-dihydro-quinoline-2-carboxylic acid methyl ester

HRID 1887978

Reaction equation

HRID 1887978 reaction equation
Br[CH2:2][C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([Cl:14])=[CH:9][CH:10]=2)[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:4]=1[C:21]([O:23][CH3:24])=[O:22].[N:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:28]([NH2:35])=[N:27][CH:26]=1.C(N(CC)C(C)C)(C)C.[H-].[Na+]>O.C1COCC1.ClCCl>[CH3:24][O:23][C:21]([C:4]1[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:6]2[C:11]([C:12](=[O:13])[C:3]=1[CH2:2][NH:35][C:28]1[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:25]=[CH:26][N:27]=1)=[CH:10][CH:9]=[C:8]([Cl:14])[CH:7]=2)=[O:22]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 847594-AminoquinazolineHCID 86672058Methyl 3-(bromomethyl)-7-chloro-4-oxo-1-phenyl-1,4-dihydroquinoline-2-carboxylate

Product 1

HCID 712084037-Chloro-4-oxo-1-phenyl-3-(quinazolin-4-ylaminomethyl)-1,4-dihydro-quinoline-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 10 mL round-bottomed flask, methyl 3-(bromomethyl)-7-chloro-4-oxo-1-phenyl-1,4-dihydroquinoline-2-carboxylate (50 mg, 0.123 mmol) was combined with dichloromethane (5 mL) to give a colorless solution. Quinazolin-4-ylamine (17.8 mg, 0.123 mmol) and N,N-diisopropylethylamine (19.1 mg, 0.148 mmol) were added. The reaction mixture was stirred at room temperature overnight. TLC showed only starting material present after this time. Sodium hydride (60% suspension) (9.8 mg, 0.264 mmol) and 2 mL of THF were added. The reaction mixture was stirred at room temperature. The reaction mixture was poured into 25 mL H2O and extracted with ethyl acetate (1×25 mL). The organic layer was washed with 1 M HCl (1×10 mL), sat aqueous NaHCO3 (1×10 mL), and H2O (1×10 mL). The organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 4 g, 30% to 100% ethyl acetate in hexanes) to yield 7-chloro-4-oxo-1-phenyl-3-(quinazolin-4-ylaminomethyl)-1,4-dihydro-quinoline-2-carboxylic acid methyl ester. MS calcd. for C26H19ClN4O3 [(M+H)+] 471.1, obsd. 471.1.

Workup

  1. customto give a colorless solution
  2. stirringThe reaction mixture was stirred at room temperature
  3. extractionextracted with ethyl acetate (1×25 mL)
  4. washThe organic layer was washed with 1 M HCl (1×10 mL)
  5. dry with materialThe organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 4 g, 30% to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3ce45c8663944ebb8fcf318ee65bd71e
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Linked notes

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