Boron tribromide → 7-(2-Hydroxyethoxy)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361280Notes

Reaction equation

HRID 2361280 reaction equation
C[O:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]3[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[C:34](=[O:35])[C:33]6[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=6)[N:27]=[CH:26]5)[C:20]=4[CH3:36])=[CH:17][N:16]=[C:15]([C:37]([NH2:39])=[O:38])[C:11]=3[NH:12]2)=[CH:8][CH:7]=1.BrB(Br)Br>ClCCl>[OH:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]3[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[C:34](=[O:35])[C:33]6[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=6)[N:27]=[CH:26]5)[C:20]=4[CH3:36])=[CH:17][N:16]=[C:15]([C:37]([NH2:39])=[O:38])[C:11]=3[NH:12]2)=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 706516047-(2-Methoxyethoxy)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 866815177-(2-Hydroxyethoxy)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 43.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 7-(2-methoxyethoxy)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (101 mg, 0.194 mmol) in dichloromethane (5 mL) at 0° C. was added tribromoborane in dichloromethane (0.622 mL, 0.622 mmol) over 5 min. The resulting heterogeneous mixture was stirred at room temperature for 1.5 hr. The reaction was quenched with ice water (15 mL). The mixture was basified with 1 N NaOH solution to pH 10 and extracted with ethyl acetate (3×40 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. After the solvent was removed under vacuum, the residue was purified by reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (44.0 mg, 0.084 mmol, 43.3% yield) as a yellow solid. The product is mixture of two atropisomers at rt. LCMS (M+H)+=506.23. 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropisomer) δ: 11.67 (s, 1H), 8.44 (s, 1H), 8.21 (s, 1H), 7.37 (s, 1H), 4.07 (m, 2H), 3.78 (m, 2H), 1.81 (s, 3H).

Workup

  1. customThe reaction was quenched with ice water (15 mL)
  2. extractionextracted with ethyl acetate (3×40 mL)
  3. extractionThe combined extract
  4. washwas washed with brine (30 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. customAfter the solvent was removed under vacuum
  7. customthe residue was purified by reverse phase HPLC
  8. concentrationThe correct fraction was concentrated under vacuum
  9. extractionextracted with ethyl acetate (3×30 mL)
  10. extractionThe combined extract
  11. washwas washed with brine (30 mL)
  12. dry with materialdried over anhydrous MgSO4
  13. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-a6f3b1b53bea446d89b850422b5722fa
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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