N1-(4-chlorophenyl)-6-methylisoquinoline-1,5-diamine → HCID 178422908, compound

HRID 1042286Notes

Reaction equation

HRID 1042286 reaction equation
Cl[C:2]1[C:7]([C:8]2[N:16]=[CH:15][N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3C2CCCCO2)=[CH:6][N:5]=[CH:4][N:3]=1.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]2[C:40]3[CH:39]=[CH:38][C:37]([CH3:41])=[C:36]([NH2:42])[C:35]=3[CH:34]=[CH:33][N:32]=2)=[CH:26][CH:25]=1>CN(C=O)C>[N:16]1[C:8]([C:7]2[C:2]([NH:42][C:36]3[C:35]4[CH:34]=[CH:33][N:32]=[C:31]([NH:30][C:27]5[CH:28]=[CH:29][C:24]([Cl:23])=[CH:25][CH:26]=5)[C:40]=4[CH:39]=[CH:38][C:37]=3[CH3:41])=[N:3][CH:4]=[N:5][CH:6]=2)=[C:9]2[C:13]([NH:12][CH:11]=[N:10]2)=[N:14][CH:15]=1

Participants

4

Reactant 2

HCID 44478904N1-(4-chlorophenyl)-6-methylisoquinoline-1,5-diamineHCID 596273686-(4-chloropyrimidin-5-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 178422908HCID 178422908, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

In a 2 mL microwave reaction tube were added 6-(4-chloropyrimidin-5-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (31 mg, 98 mop and N1-(4-chlorophenyl)-6-methylisoquinoline-1,5-diamine (28 mg, 98 μmol) in DMF (0.6 mL). The mixture was thoroughly mixed and flushed with argon then sealed. It was stirred at 70° C. The temperature was raised to 90° C. after 2 hrs and allowed over night. The reaction mixture was partitioned in EtOAc and NaHCO3. The organic layer was washed with brine and dried over Na2SO4. The residue was treated with MeOH (3 mL) and conc HCl (0.2 mL). The mixture was stirred for 2 hrs, then partitioned between NaHCO3 and EtOAc (10 mL each). The organic layer was collected and purified by prep HPLC (MeCN/H2O=5-95% with 0.1% TFA). Desired fractions were combined and neutralized with NaHCO3 (sat., aq.) and extracted with DCM. The DCM layer was washed with brine then dried over Na2SO4, then dried over a stream of N2 to give a yellow solid N5-(5-(9H-purin-6-yl)pyrimidin-4-yl)-N1-(4-chlorophenyl)-6-methylisoquinoline-1,5-diamine. MS Found: (ESI pos. ion) m/z 480 (M+H+).

Workup

  1. additionThe mixture was thoroughly mixed
  2. customflushed with argon
  3. customthen sealed
  4. temperatureThe temperature was raised to 90° C. after 2 hrs
  5. waitallowed over night
  6. customThe reaction mixture was partitioned in EtOAc
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. additionThe residue was treated with MeOH (3 mL) and conc HCl (0.2 mL)
  10. stirringThe mixture was stirred for 2 hrs
  11. custompartitioned between NaHCO3 and EtOAc (10 mL each)
  12. customThe organic layer was collected
  13. custompurified by prep HPLC (MeCN/H2O=5-95% with 0.1% TFA)
  14. extractionextracted with DCM
  15. washThe DCM layer was washed with brine
  16. dry with materialthen dried over Na2SO4
  17. dry with materialdried over a stream of N2

Sources & evidence

ORD record
ord-1d0be9e8a3104dcfb6edfe089789d709
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

Loading…