4-Chloroaniline → HCID 178422910, compound

HRID 1042295Notes

Reaction equation

HRID 1042295 reaction equation
[CH3:1][C:2]1[C:11]([NH:12][C:13]2[C:18]([C:19]3[N:27]=[CH:26][N:25]=[C:24]4[C:20]=3[N:21]=[CH:22][N:23]4C3CCCCO3)=[CH:17][CH:16]=[CH:15][N:14]=2)=[C:10]2[C:5]([C:6](SC)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([NH2:43])=[CH:39][CH:38]=1>C(O)(C(F)(F)F)=O.O1CCOCC1>[N:27]1[C:19]([C:18]2[C:13]([NH:12][C:11]3[C:2]([CH3:1])=[CH:3][CH:4]=[C:5]4[C:10]=3[N:9]=[CH:8][N:7]=[C:6]4[NH:43][C:40]3[CH:41]=[CH:42][C:37]([Cl:36])=[CH:38][CH:39]=3)=[N:14][CH:15]=[CH:16][CH:17]=2)=[C:20]2[C:24]([NH:23][CH:22]=[N:21]2)=[N:25][CH:26]=1

Participants

5

Reactant 2

HCID 78124-ChloroanilineHCID 59627367HCID 59627367, compound

Product 1

HCID 178422910HCID 178422910, compound

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

A clear microwave vial was charged with 7-methyl-4-(methylthio)-N-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)quinazolin-8-amine (0.200 g, 0.413 mmol) and 4-chlorobenzenamine (0.105 g, 0.825 mmol) and 5 ml of dioxane. A few drops of TFA was added to the mixture and the reaction vial was capped. The vial was heated in a microwave reactor at 160° C. for 12 minutes. The solid that crashed out of the reaction mixture was filtered off and washed with ethyl acetate. The solid was dissolved in DMSO (3 ml) and purified by RP-HPLC using a gradient of 5% ACN 0.1% TFA to 95% ACN 0.1% TFA in water 0.1% TFA. The pure fractions were neutralized with ammonium hydroxide and the volatiles were removed under reduced pressure. The solid that crashed out of the aqueous layer was filtered off, washed with water and dried in a vacuum oven at 45 degrees to give N8-(3-(9H-purin-6-yl)pyridin-2-yl)-N4-(4-chlorophenyl)-7-methylquinazoline-4,8-diamine as a yellow solid. MS Found: (ESI pos. ion) m/z 480 (M+H+).

Workup

  1. customthe reaction vial was capped
  2. filtrationwas filtered off
  3. washwashed with ethyl acetate
  4. dissolutionThe solid was dissolved in DMSO (3 ml)
  5. custompurified by RP-HPLC
  6. customthe volatiles were removed under reduced pressure
  7. filtrationwas filtered off
  8. washwashed with water
  9. customdried in a vacuum oven at 45 degrees

Sources & evidence

ORD record
ord-46ed1ee756e349c1b7ba289f8167dfc4
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

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