Ethyl Acetate → HCID 67995034, compound

HRID 2361307Notes

Reaction equation

HRID 2361307 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:35])=[C:14]([C:18]4[C:30]5[C:29]6[C:24](=[CH:25][C:26]([OH:31])=[CH:27][CH:28]=6)[NH:23][C:22]=5[C:21]([C:32]([NH2:34])=[O:33])=[N:20][CH:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1.[C:36](=[O:39])([O-])[O-].[Cs+].[Cs+].[C:42](OCC)(=O)[CH3:43]>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:35])=[C:14]([C:18]4[C:30]5[C:29]6[C:24](=[CH:25][C:26]([O:31][CH2:42][CH2:43][CH2:36][OH:39])=[CH:27][CH:28]=6)[NH:23][C:22]=5[C:21]([C:32]([NH2:34])=[O:33])=[N:20][CH:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 178422184HCID 178422184, compound

Product 1

HCID 67995034HCID 67995034, compoundYield 16.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 4-(3-(6-chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-hydroxy-9H-pyrido[3,4-b]indole-1-carboxamide (32 mg, 0.066 mmol) and cesium carbonate (25.9 mg, 0.080 mmol) in DMF (3 mL) was heated at 75° C. for 4 hr. The mixture was diluted with ethyl acetate (60 mL), washed with water (2×20 mL) and brine (20 mL), and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum and 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 (6.2 mg, 0.011 mmol, 16.6% yield) as a yellow solid. LCMS (M+H)+=541.28. 1H NMR (500 MHz, DMSO-d6) δ: 11.70 (s, 1H), 8.35 (s, 1H), 8.24 (s, 1H), 7.87 (s, 1H), 7.80-7.78 (m, 3H), 7.72 (m, 1H), 7.59 (m, 1H), 7.50 (m, 1H), 7.41 (d, J=2.2 Hz, 1H), 7.19 (d, J=8.9 Hz, 1H), 6.74 (dd, J1=8.9 Hz, J2=2.4 Hz, 1H), 5.09 (d, J=17.5 Hz, 1H), 5.00 (d, J=17.5 Hz, 1H), 4.17 (m, 2H), 3.65 (m, 2H), 1.97 (m, 2H), 1.92 (s, 3H).

Workup

  1. washwashed with water (2×20 mL) and brine (20 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. concentrationThe organic solution was concentrated under vacuum
  4. customthe residue was purified by reverse phase HPLC
  5. concentrationThe correct fraction was concentrated under vacuum
  6. extractionextracted with ethyl acetate (3×30 mL)
  7. extractionThe combined extract
  8. washwas washed with brine (30 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-9ec504fb245141e792951e19c288ca81
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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