Sodium Chloride → 4Diethylamino-but-2-enoic acid [4(3-bromo-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide

HRID 1935052Notes

Reaction equation

HRID 1935052 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:25][CH2:26][N:27]([CH:31]([CH3:33])C)[CH:28]([CH3:30])C.BrC/C=[CH:37]/[C:38](Cl)=[O:39].[Na+].[Cl-].C(NCC)C.C(=O)(O)[O-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([NH:20][C:38](=[O:39])[CH:37]=[CH:33][CH2:31][N:27]([CH2:26][CH3:25])[CH2:28][CH3:30])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 6

HCID 5234Sodium ChlorideHCID 8021DiethylamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 11263885(E)-4-Bromo-2-butenoyl ChlorideHCID 224666136-Amino-4-[(3-bromo-4-fluorophenyl)amino]-7-methoxy-3-quinolinecarbonitrile

Product 1

HCID 544873344Diethylamino-but-2-enoic acid [4(3-bromo-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amideYield 38.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of 0.77 g (1.98 mmol) of 4-[(3-bromo-4-fluorophenyl)amino]-7-methoxy-6-amino-quinoline-3-carbonitrile and 3.5 ml (20 mmol) of Hunig's base in 35 ml of dry THF at 0° C., with stirring, was added a THF solution containing 2.2 g (12 mmol) of 4-bromo crotonyl chloride dropwise. The mixture was stirred for additional 30 minutes at 0° C. 50 ml of saturated NaCl solution was added to the reaction mixture, then it was extracted with ethyl acetate. The ethyl acetate solution was dried over sodium sulfate and then was added to a solution of 3.1 ml (30 mmol) of diethyl amine in 5 ml of THF at 0° C. dropwise. The solution was stirred an additional hour at 0° C. and 30 minutes at room temperature. The mixture was poured into diluted sodium bicarbonate solution . The organic layer was dried over sodium sulfate and solvent was removed under vacuum. The residue was chromatographed to give 0.4 g off-white solid: mass spectrum (electrospray, m/e): M+H 525.9 and 527.9.

Workup

  1. stirringThe mixture was stirred for additional 30 minutes at 0° C
  2. extractionit was extracted with ethyl acetate
  3. dry with materialThe ethyl acetate solution was dried over sodium sulfate
  4. stirringThe solution was stirred an additional hour at 0° C. and 30 minutes at room temperature
  5. dry with materialThe organic layer was dried over sodium sulfate and solvent
  6. customwas removed under vacuum
  7. customThe residue was chromatographed

Sources & evidence

ORD record
ord-a39c0246f7f44aa2aea6e9c951ea464e
Source dataset
uspto-grants-2002_05
Patent number
US06384051B1

Reaction notes

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