Boron tribromide dichloromethane → HCID 70651414, compound

HRID 2361382Notes

Reaction equation

HRID 2361382 reaction equation
C[O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[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])=[N:17][N:16]=[C:15]([C:37]([NH2:39])=[O:38])[C:11]=3[NH:12][C:13]=2[CH:14]=1.BrB(Br)Br.ClCCl>ClCCl.CO>[OH:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[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])=[N:17][N:16]=[C:15]([C:37]([NH2:39])=[O:38])[C:11]=3[NH:12][C:13]=2[CH:14]=1

Participants

5

Reactant 2

HCID 22277759Boron tribromide dichloromethaneHCID 67994899HCID 67994899, compound

Product 1

HCID 70651414HCID 70651414, compoundYield 18.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a homogeneous, light orange solution of 7-(2-methoxyethoxy)-1-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-5H-pyridazino[4,5-b]indole-4-carboxamide (0.0973 g, 0.155 mmol) in dichloromethane (5 ml) under nitrogen at 0° C. was added 1M tribromoborane/dichoromethane (0.496 ml, 0.496 mmol) over 5 min. After 5 min, the cold bath was removed, and the heterogeneous solution was stirred to room temperature. One hour later, the reaction was immersed in an ice-water bath and ice water (15 mL) was added. The resulting mixture was basified with 1 N aqueous NaOH solution to pH ˜10 by litmus paper. EtOAc (50 mL) was added, and the layers were separated. The aqueous layer was extracted with EtOAc (2×50 mL). The combined extract was dried over MgSO4 and concentrated in vacuo to give a residue which was diluted with MeOH (1 mL) and purified by reverse phase HPLC. The appropriate fractions were collected, basified with NaHCO3 (solid), and concentrated in vacuo. The residue was extracted with CH2Cl2 (3×). The combined extract was dried over Na2SO4 and concentrated in vacuo to give the desired product (0.0148 g, 0.029 mmol, 18.8% yield) as a light yellow solid. LC/MS (M+H)=507.21; 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropoisomer) δ ppm 12.23 (s, 1H), 8.71 (br. S, 1H), 8.48 (s, 1H), 8.26 (t, J=6.2 Hz, 1H), 8.00 (br. S, 1H), 7.88-7.94 (m, 1H), 7.79 (d, J=8.0 Hz, 1H)), 7.72-7.77 (m, 1H), 7.58-7.70 (m, 3H), 7.41 (d, J=2.2 Hz, 1H), 7.29 (d, J=8.6 Hz, 1H), 6.88 (dd, J1=8.9, J2=2.2 Hz, 1H), 4.84-4.97 (m, 1H), 4.01-4.14 (m, 2H), 3.71-3.85 (m, 2H), 1.81 (s, 3H).

Workup

  1. customthe cold bath was removed
  2. customOne hour later, the reaction was immersed in an ice-water bath
  3. additionice water (15 mL) was added
  4. additionEtOAc (50 mL) was added
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  7. extractionThe combined extract
  8. dry with materialwas dried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customto give a residue which
  11. custompurified by reverse phase HPLC
  12. customThe appropriate fractions were collected
  13. concentrationconcentrated in vacuo
  14. extractionThe residue was extracted with CH2Cl2 (3×)
  15. extractionThe combined extract
  16. dry with materialwas dried over Na2SO4
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-74e0e790e1b14a6d80b7e995590a0f5c
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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