Toluene → HCID 59729986, compound

HRID 492414Notes

Reaction equation

HRID 492414 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]([N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([OH:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1)=[O:4].Cl[C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][N:21]=1.C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>CN(C=O)C>[F:18][C:2]([F:1])([F:17])[C:3]([N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([O:16][C:20]3[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][N:21]=3)[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1)=[O:4]

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 804566-ChloronicotinamideHCID 59730230HCID 59730230, compound

Product 1

HCID 59729986HCID 59729986, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Add 2,2,2-trifluoro-1-(7-hydroxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)ethanone (0.750 g, 2.89 mmol), 6-chloronicotinamide (0.377 g, 2.41 mmol) and K2CO3 (0.833 g, 6.03 mmol) to a round bottom equipped with a Dean-Stark trap. Add toluene (6 mL) and DMF (18 mL). Heat at reflux for two hours. Cool the reaction mixture to 100° C. and stir overnight. Remove the toluene and DMF as an azeotrope with xylenes. Suspend the solid in 5% methanol/ethyl acetate (100 mL) and filter. Wash the filter cake with ethyl acetate. Concentrate the filtrate, then purify by flash chromatography, eluting with 40% ethyl acetate in dichloromethane to give the title compound (0.312 g, 34.0%): MS ES+ 380 (M+H)+; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=8.5 min, 89% purity.

Workup

  1. custombottom equipped with a Dean-Stark trap
  2. temperatureHeat
  3. temperatureat reflux for two hours
  4. customRemove the toluene and DMF as an azeotrope with xylenes
  5. filtrationfilter
  6. washWash the filter cake with ethyl acetate
  7. concentrationConcentrate the filtrate
  8. custompurify by flash chromatography
  9. washeluting with 40% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-dc6bbf9946614b33b693413d98f7760c
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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