Sodium Iodide → HCID 56592044, compound

HRID 714583Notes

Reaction equation

HRID 714583 reaction equation
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([NH:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH:19]1[CH2:23][CH2:22][O:21][CH2:20]1)[N:14]=[CH:13][C:12]([C:24]#[N:25])=[C:11]2[NH:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)=[C:29]([Cl:41])[CH:28]=1)=[O:6].[Na+].[I-].Cl.[CH3:45][NH:46][CH3:47].C(=O)([O-])[O-].[K+].[K+].C([O-])(O)=O.[Na+]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:41][C:29]1[CH:28]=[C:27]([NH:26][C:11]2[C:10]3[C:15](=[CH:16][C:17]([O:18][CH:19]4[CH2:23][CH2:22][O:21][CH2:20]4)=[C:8]([NH:7][C:5](=[O:6])/[CH:4]=[CH:3]/[CH2:2][N:46]([CH3:47])[CH3:45])[CH:9]=3)[N:14]=[CH:13][C:12]=2[C:24]#[N:25])[CH:32]=[CH:31][C:30]=1[O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 10473Dimethylamine, hydrochlorideHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 56592043HCID 56592043, compound

Product 1

HCID 56592044HCID 56592044, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

(E)-4-bromo-N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)-2-butenamide (2.35 g, 3.704 mmol) was dissolved in DMF (chromatographically pure) (40 mL). The solution was cooled in an ice-water bath under argon atmosphere. To the solution was added NaI (278 mg, 1.852 mmol). The mixture was stirred for 30 min. To the mixture were added dimethylamine hydrochloride (604 mg, 7.408 mmol), potassium carbonate (2.556 g, 18.519 mmol) and tetrabutyl ammonium iodide (59 mg, 0.185 mmol). The resultant mixture was stirred at the room temperature overnight. After the reaction finished, the reaction solution was poured into staturated NaHCO3 solution (400 mL) to precipitate a yellow solid. The solid was extracted with ethyl acetate three times (550 mL in total). The ethyl acetate layers were combined. The organic phase was washed with water (300 mL) and saturated NaCl solution (300 mL), successively. The resultant organic phase was dried over anhydrous MgSO4 for half-hour, filtered and rotary-evaporated to dryness. The resultant substance was purified with column chromatography (eluent: chloroform:methanol=9:1) to give a yellow solid (1.375 g). Yield: 62.0%.

Workup

  1. temperatureThe solution was cooled in an ice-water bath under argon atmosphere
  2. customto precipitate a yellow solid
  3. extractionThe solid was extracted with ethyl acetate three times (550 mL in total)
  4. washThe organic phase was washed with water (300 mL) and saturated NaCl solution (300 mL)
  5. dry with materialThe resultant organic phase was dried over anhydrous MgSO4 for half-hour
  6. filtrationfiltered
  7. customrotary-evaporated to dryness
  8. customThe resultant substance was purified with column chromatography (eluent: chloroform:methanol=9:1)

Sources & evidence

ORD record
ord-c0ba2b364a8748a08de50b873b9f9b7c
Source dataset
uspto-grants-2015_11
Patent number
US09187458B2

Reaction notes

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