4-(2-Methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-7-(2-oxoethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide → 7-(2-Hydroxypropoxy)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361284Notes

Reaction equation

HRID 2361284 reaction equation
[CH3:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:19]1[C:31]2[C:30]3[C:25](=[CH:26][C:27]([O:32][CH2:33][CH:34]=[O:35])=[CH:28][CH:29]=3)[NH:24][C:23]=2[C:22]([C:36]([NH2:38])=[O:37])=[N:21][CH:20]=1.[CH3:39][Mg]Br>O1CCCC1>[OH:35][CH:34]([CH3:39])[CH2:33][O:32][C:27]1[CH:26]=[C:25]2[C:30]([C:31]3[C:19]([C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([N:8]5[C:17](=[O:18])[C:16]6[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=6)[N:10]=[CH:9]5)[C:2]=4[CH3:1])=[CH:20][N:21]=[C:22]([C:36]([NH2:38])=[O:37])[C:23]=3[NH:24]2)=[CH:29][CH:28]=1

Participants

4

Reactant 2

HCID 866815184-(2-Methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-7-(2-oxoethoxy)-9H-pyrido[3,4-b]indole-1-carboxamideHCID 178418573HCID 178418573, compound2×

Product 1

HCID 679948617-(2-Hydroxypropoxy)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 4.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-7-(2-oxoethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide (178 mg, 85% purity, 0.300 mmol) in tetrahydrofuran (10 mL) at 0° C. was added methylmagnesium bromide (0.707 mL, 2.121 mmol). The mixture was stirred at rt for 20 min. Additional methylmagnesium bromide (0.50 mL, 1.50 mmol) was added. The mixture was stirred at room temperature for another 20 min and then the reaction was quenched with water (20 mL). The resulting mixture was extracted with ethyl acetate (3×40 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. After solvent was removed under vacuum, the residue was purified by reverse phase HPLC. The correct fractions were combined and concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (7.6 mg, 0.014 mmol, 4.9% yield) as a yellow solid. LCMS (M+H)+=520.21. 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropisomer) δ: 11.68 (s, 1H), 8.44 (s, 1H), 8.21 (s, 1H), 7.36 (s, 1H), 4.01 (m, 1H), 3.92-3.84 (m, 2H), 1.81 (s, 3H).

Workup

  1. stirringThe mixture was stirred at room temperature for another 20 min
  2. customthe reaction was quenched with water (20 mL)
  3. extractionThe resulting mixture was extracted with ethyl acetate (3×40 mL)
  4. extractionThe combined extract
  5. washwas washed with brine (30 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. customAfter solvent was removed under vacuum
  8. customthe residue was purified by reverse phase HPLC
  9. concentrationconcentrated under vacuum
  10. extractionextracted with ethyl acetate (3×35 mL)
  11. extractionThe combined extract
  12. washwas washed with brine (30 mL)
  13. dry with materialdried over anhydrous MgSO4
  14. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-4632efbf9e394009bfe412519eac64bf
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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