3-Fluoroaniline → HCID 11858025, compound

HRID 1993351Notes

Reaction equation

HRID 1993351 reaction equation
Cl[C:2]1[N:7]([CH3:8])[C:6](=[O:9])[C:5]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:29][CH3:30])=[C:24]([O:27][CH3:28])[CH:25]=4)[N:20]=[CH:19][CH:18]=3)=[C:12]([F:31])[CH:11]=2)=[CH:4][N:3]=1.[F:32][C:33]1[CH:34]=[C:35]([CH:37]=[CH:38][CH:39]=1)[NH2:36]>O1CCOCC1.Cl>[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[O:29][CH3:30])[N:20]=[CH:19][CH:18]=[C:17]2[O:16][C:13]1[CH:14]=[CH:15][C:10]([C:5]2[C:6](=[O:9])[N:7]([CH3:8])[C:2]([NH:36][C:35]3[CH:37]=[CH:38][CH:39]=[C:33]([F:32])[CH:34]=3)=[N:3][CH:4]=2)=[CH:11][C:12]=1[F:31]

Participants

5

Reactant 2

HCID 97423-FluoroanilineHCID 68421745HCID 68421745, compound

Product 1

HCID 11858025HCID 11858025, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

The crude 2-chloro-5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-3-methylpyrimidin-4(3H)-one from Step 3 was dissolved in 15 mL 1,4-dioxane. To 5 mL of this solution was added m-fluoroaniline (0.2 mL) and concentrated HCl (1 drop). The reaction was heated in the microwave at 60° C. and 60 W for 5 min before being cooled to RT. The mixture was concentrated and filtered through a 1 inch plug of silica gel with EtOAc→2:1 EtOAc/MeOH→3:2 MeOH/EtOAc. The filtrate was concentrated and purified using reverse phase HPLC (10%→95% MeCN/H2O with 0.1% TFA). Finally, the compound was filtered again through a 1-inch plug of silica gel in a pipette column with EtOAc to give the title compound. MS (ESI pos. ion) m/z: 517. Calc'd for C28H22F2N4O4: 516.16.

Workup

  1. temperature60 W for 5 min before being cooled to RT
  2. concentrationThe mixture was concentrated
  3. filtrationfiltered through a 1 inch plug of silica gel with EtOAc→2:1 EtOAc/MeOH
  4. concentrationThe filtrate was concentrated
  5. custompurified
  6. filtrationFinally, the compound was filtered again through a 1-inch plug of silica gel in a pipette column with EtOAc

Sources & evidence

ORD record
ord-2064844ff1db4522aa47e3f5838b9df9
Source dataset
uspto-grants-2010_01
Patent number
US07652009B2

Reaction notes

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