Sodium Chloride → HCID 54145573, compound

HRID 612131Notes

Reaction equation

HRID 612131 reaction equation
[Cl: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].C[CH2:26][N:27]([CH:31]([CH3:33])C)[CH:28](C)C.BrC/C=[CH:37]/[C:38](Cl)=[O:39].[Cl-].[Na+]>C1COCC1>[Cl: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]([CH3:26])[CH3:28])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 81531DiisopropylethylamineHCID 111424366-Amino-4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrileHCID 11263885(E)-4-Bromo-2-butenoyl Chloride

Product 1

HCID 54145573HCID 54145573, compoundYield 61.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 1.08 g (3.1 mmol) of 4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-amino-quinoline-3-carbonitrile and 1.7 ml (9.7 mmol) of Hunig's base in 30 ml of dry THF at 0° C., with stirring, was added a THF solution containing 1.99 g (9.3 mmol) of 4-bromo crotonyl chloride dropwise. The mixture was stirred for additional 0.5 hour at 0° C. under nitrogen. 50 ml of saturated sodium chloride solution was introduced to the reaction mixture, then it was extracted with ethyl acetate. The ethyl acetate solution was separated and dried over sodium sulfate and then it was added to 31 ml of dimethyl amine solution (2.0 M in THF) at 0° C. dropwise. After addition, the solution was stirred for another hour at room temperature. The mixture was poured into diluted sodium bicarbonate solution. The organic layer was separated and the residue was chromatographed to give 0.86 grams of white solid: mass spectrum (electrospray, m/e):

Workup

  1. stirringThe mixture was stirred for additional 0.5 hour at 0° C. under nitrogen
  2. extractionit was extracted with ethyl acetate
  3. customThe ethyl acetate solution was separated
  4. dry with materialdried over sodium sulfate
  5. additionit was added to 31 ml of dimethyl amine solution (2.0 M in THF) at 0° C. dropwise
  6. additionAfter addition
  7. stirringthe solution was stirred for another hour at room temperature
  8. additionThe mixture was poured into diluted sodium bicarbonate solution
  9. customThe organic layer was separated
  10. customthe residue was chromatographed

Sources & evidence

ORD record
ord-bb1541a02f0d46ceb3dd31114f9be5e7
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

Loading…