HCID 67995196, compound → HCID 70651625, compound

HRID 2361391Notes

Reaction equation

HRID 2361391 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[CH2:31][C:30]6[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][CH:29]=6)[C:24]5=[O:34])[C:18]=4[CH3:35])=[N:15][N:14]=[C:13]([C:36]([NH2:38])=[O:37])[C:9]=3[NH:10][C:11]=2[CH:12]=1)(=[O:3])[CH3:2].[CH3:39][Mg]Br>O1CCCC1>[OH:3][C:1]([C:4]1[CH:5]=[CH:6][C:7]2[C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[CH2:31][C:30]6[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][CH:29]=6)[C:24]5=[O:34])[C:18]=4[CH3:35])=[N:15][N:14]=[C:13]([C:36]([NH2:38])=[O:37])[C:9]=3[NH:10][C:11]=2[CH:12]=1)([CH3:39])[CH3:2]

Participants

4

Reactant 2

HCID 67995196HCID 67995196, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 70651625HCID 70651625, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-acetyl-1-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-5H-pyridazino[4,5-b]indole-4-carboxamide (36.0 mg, 0.071 mmol) in tetrahydrofuran (8 mL) at 0° C. was added methylmagnesium bromide (0.119 mL, 0.356 mmol). The mixture was stirred at room temperature for 20 min. Additional methylmagnesium bromide (0.119 mL, 0.356 mmol) was added at 0° C. and the mixture was stirred at room temperature for another 20 min. The reaction was quenched with water (15 mL). The resulting mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 mL) and dried over anhydrous MgSO4. After 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 (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (11.4 mg, 0.021 mmol, 30.1% yield) as a white solid. LCMS (M+H)+=522.20. 1H NMR (500 MHz, DMSO-d6) δ: 12.34 (s, 1H), 8.75 (s, 1H), 8.07 (s, 1H), 8.00 (s, 1H), 7.73 (d, J=6.9 Hz, 1H), 7.61-7.57 (m, 2H), 7.51 (d, J=6.4 Hz, 1H), 7.35-7.33 (m, 2H), 7.27-7.25 (m, 2H), 5.19 (s, 1H), 4.98 (d, J=16.9 Hz, 1H), 4.90 (d, J=16.9 Hz, 1H), 3.86 (s, 3H), 1.90 (s, 3H), 1.49 (s, 6H).

Workup

  1. stirringthe mixture was stirred at room temperature for another 20 min
  2. customThe reaction was quenched with water (15 mL)
  3. extractionThe resulting mixture was extracted with ethyl acetate (3×30 mL)
  4. extractionThe combined extract
  5. washwas washed with brine (25 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. concentrationThe correct fraction was concentrated 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-39af61ceb25c44598544637f26d309b8
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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