Methyl iodide → HCID 59427307, compound

HRID 1013767Notes

Reaction equation

HRID 1013767 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([NH:18][C:19]3[CH:36]=[CH:35][C:22]([O:23][C:24]4[CH:25]=[CH:26][N:27]=[C:28]5[C:33]=4[NH:32][C:31](=[O:34])[CH:30]=[CH:29]5)=[CH:21][CH:20]=3)=[N:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:40]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([N:18]([CH3:40])[C:19]3[CH:20]=[CH:21][C:22]([O:23][C:24]4[CH:25]=[CH:26][N:27]=[C:28]5[C:33]=4[NH:32][C:31](=[O:34])[CH:30]=[CH:29]5)=[CH:35][CH:36]=3)=[N:10][N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67316096HCID 67316096, compound

Product 1

HCID 59427307HCID 59427307, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a 20 mL sealed tube, was dissolved 8-(4-(4-(4-chlorophenyl)phthalazin-1-ylamino)phenoxy)-1,5-naphthyridin-2(1H)-one (0.25 g, 0.508 mmol) in THF (2.2 mL), and the mixture was cooled to 0° C. Sodium Hydride, 60% in mineral oil (0.045 g, 1.12 mmol), was added and the mixture was stirred at 0° C. for 1 hour. Iodomethane (0.070 mL, 1. 12 mmol), was added and the mixture was warmed to 60° C., and stirred for 3 hours. A mixture of products was revealed by LC/MS. The mixture was cooled to RT, quenched with water, extracted into ethyl acetate, washed 1× water, 1× NaCl, dried with Na2SO4, filtered through fritted funnel, and filtrate was concentrated. The crude concentrate was purified by reverse phase chromatography. The product containing fractions were extracted into DCM, washed 1× sodium carbonate, 1×H2O, dried with Na2SO4, filtered through fritted funnel, and the filtrate was concentrated down to a light yellow solid containing two methylated products. The solids were suspended in methanol, filtered, rinsed with methanol, and air dried to yield 8-(4-((4-(4-chlorophenyl)phthalazin-1-yl)(methyl)amino)phenoxy)-1,5-naphthyridin-2(1H)-one. MS: [M+H]=506.0; Calc'd 505.9 for C29H20ClN5O2.

Workup

  1. customIn a 20 mL sealed tube
  2. temperaturethe mixture was warmed to 60° C.
  3. stirringstirred for 3 hours
  4. additionA mixture of products
  5. temperatureThe mixture was cooled to RT
  6. customquenched with water
  7. extractionextracted into ethyl acetate
  8. washwashed 1× water, 1× NaCl
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered through fritted funnel
  11. concentrationfiltrate was concentrated
  12. concentrationThe crude concentrate
  13. customwas purified by reverse phase chromatography
  14. additionThe product containing fractions
  15. extractionwere extracted into DCM
  16. washwashed 1× sodium carbonate, 1×H2O
  17. dry with materialdried with Na2SO4
  18. filtrationfiltered through fritted funnel
  19. concentrationthe filtrate was concentrated down to a light yellow solid
  20. additioncontaining two methylated products
  21. filtrationfiltered
  22. washrinsed with methanol, and air
  23. customdried

Sources & evidence

ORD record
ord-c25225b6b23b4e5a89f8eb5d008ca58b
Source dataset
uspto-grants-2011_07
Patent number
US07981891B2

Reaction notes

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