Dimethylformamide → HCID 67494898, compound

HRID 1500223Notes

Reaction equation

HRID 1500223 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([CH3:14])[C:6]([C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)=[CH:17][C:16]=1[F:33])=[C:5]2[O:34]CC.FC1C=C(OC2C=CC(OC(F)(F)F)=CC=2)C=CC=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[NH:8][C:7]([CH3:14])=[C:6]([C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:31])([F:32])[F:30])=[CH:26][CH:27]=3)=[CH:17][C:16]=1[F:33])[C:5]2=[O:34]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 67494592HCID 67494592, compoundHCID 67495770HCID 67495770, compound

Product 1

HCID 67494898HCID 67494898, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
90 °C

Procedure

An oven-dried Schlenk tube was flame-dried and backfilled with argon (X3). The tube was then charged with 6-chloro-4-ethoxy-3-(2-fluoro-4-(4-(trifluoromethoxy)phenoxy)phenyl)-7-methoxy-2-methylquinoline (0.3 g, 0.8 mmol), Pd(PPh3)4 (0.08 g, 10 mol %), and 2-fluoro-4-(4-(trifluoromethoxy)phenoxy)phenylboronic acid (0.375 g, 1.2 mmol). A rubber septum was then placed on the tube and 2M Na2CO3 (3 mL), DMF (15 mL), were added. The tube was then purged of air by argon for about 1 minute, while stirring and then heated at 90° C. until completion by HPLC analysis ˜3 h. After completion, reaction was boiled with 1:1 MeOH/CHCl3, and filtered over celite. The celite was then rinsed with boiling hot DMF. The filtrate was then evaporated on silica gel purified via flash chromatography (33% EtOAc in Hexane). The resulting amorphous solid (0.48 g, 52%) was then dissolved in 4.8 mL of AcOH and 4.8 mL of HBr. This solution was refluxed for 1.5 h. The reaction was poured onto ice and water. The resulting solid was filtered via filtration and recrystallized from DMF twice (0.2 g, 44%).

Workup

  1. customAn oven-dried Schlenk tube was flame-dried
  2. additionwere added
  3. customThe tube was then purged of air by argon for about 1 minute
  4. customAfter completion, reaction
  5. filtrationfiltered over celite
  6. washThe celite was then rinsed
  7. customThe filtrate was then evaporated on silica gel
  8. custompurified via flash chromatography (33% EtOAc in Hexane)
  9. dissolutionThe resulting amorphous solid (0.48 g, 52%) was then dissolved in 4.8 mL of AcOH
  10. temperatureThis solution was refluxed for 1.5 h
  11. additionThe reaction was poured onto ice and water
  12. filtrationThe resulting solid was filtered via filtration
  13. customrecrystallized from DMF twice (0.2 g, 44%)

Sources & evidence

ORD record
ord-26aaf903194a49adad5019e63ca2af9e
Source dataset
uspto-grants-2015_12
Patent number
US09206131B2

Reaction notes

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