Isopropanol → 5-Chloro-N4-(4-methoxyphenyl)-N4-methyl-9H-pyrimido[4,5-b]indole-2,4-diamine

HRID 2172892Notes

Reaction equation

HRID 2172892 reaction equation
Cl[C:2]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3[Cl:15])[NH:7][C:6]=2[N:5]=[C:4]([NH:16]C(=O)C(C)(C)C)[N:3]=1.[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([NH:29][CH3:30])=[CH:27][CH:26]=1.C(O)(C)C>Cl.CC(C)=O.CO>[Cl:15][C:12]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:13]=1[C:14]1[C:2]([N:29]([C:28]3[CH:31]=[CH:32][C:25]([O:24][CH3:23])=[CH:26][CH:27]=3)[CH3:30])=[N:3][C:4]([NH2:16])=[N:5][C:6]=1[NH:7]2

Participants

7

Reactant 3

HCID 3776Isopropanol2×HCID 22250N-Methyl-4-anisidineHCID 45103998HCID 45103998, compound

Product 1

HCID 533590735-Chloro-N4-(4-methoxyphenyl)-N4-methyl-9H-pyrimido[4,5-b]indole-2,4-diamineYield 69%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 180AcetoneSolventHCID 887MethanolSolvent

Conditions

Temperature
115 °C

Procedure

To 10 (20 mg, 0.06 mmol) was added 4-methoxy-N-methyl aniline (61 mg, 0.44 mmol), 50 mL of Isopropanol, and 4 drops of conc. HCl in a 100 mL round bottom flask. The reaction mixture was refluxed at 110-120° C. for 26 hours, following which the Isopropanol was evaporated and the mixture was basified with ammonia in methanol to obtain a slight precipitate. The resulting precipitate was then dissolved in acetone and methanol. To the solution was added silica, and the solvent was removed under reduced pressure to provide a silica gel plug. The plug was transferred on top of a column packed with silica gel, twenty times the weight of plug, eluted with chloroform and 1% methanol in chloroform. Fractions containing the product AAG13 (TLC) were pooled and evaporated to give a solid which was further purified by washing with hexane. The overall yield was 69%. TLC Rf 0.25 (chloroform-methanol 20:1), m.p. 163-164° C., 1H NMR: δ 3.30 (s, 3H, OCH3), 3.66 (s, 3H, N—CH3), 6.55 (s, 2H, NH2, exch), 6.76-7.25 (m, 7H, ArH), 11.65 (s, 1H, 9-NH, exch). Anal. Calculated (C18H16ClN5O. 0.2 CH3(CH2)4—CH3): C, 62.15; H, 5.10; N, 18.87; Cl, 9.55. Found: C, 61.79; H, 4.95; N, 18.72; Cl, 9.48.

Workup

  1. customwas evaporated
  2. customto obtain a slight precipitate
  3. additionTo the solution was added silica
  4. customthe solvent was removed under reduced pressure
  5. customto provide a silica gel plug
  6. washeluted with chloroform and 1% methanol in chloroform
  7. additionFractions containing the product AAG13 (TLC)
  8. customevaporated
  9. customto give a solid which
  10. customwas further purified
  11. washby washing with hexane

Sources & evidence

ORD record
ord-b4b5864f79b44f869ffad95cafa12697
Source dataset
uspto-grants-2015_06
Patent number
US09056869B2

Reaction notes

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