Potassium Carbonate → HCID 59375153, compound

HRID 661952Notes

Reaction equation

HRID 661952 reaction equation
[OH:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[C:7]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([N:24]5[CH2:32][C:31]6[C:26](=[CH:27][C:28]([CH3:33])=[CH:29][CH:30]=6)[C:25]5=[O:34])[C:19]=4[CH3:35])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.[C:36](=[O:39])([O-])[O-].[K+].[K+].Br[CH2:43][CH:44]1[CH2:46][O:45]1>CN(C=O)C>[OH:45][CH:44]([CH2:46][O:39][CH3:36])[CH2:43][O:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[C:7]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([N:24]5[CH2:32][C:31]6[C:26](=[CH:27][C:28]([CH3:33])=[CH:29][CH:30]=6)[C:25]5=[O:34])[C:19]=4[CH3:35])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18430EpibromohydrinHCID 66606478HCID 66606478, compound

Product 1

HCID 59375153HCID 59375153, compoundYield 13.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 7-hydroxy-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 40-2, 30 mg, 0.065 mmol) and potassium carbonate (36 mg, 0.260 mmol) in DMF (1.0 mL) was stirred at rt for 30 min, then was treated with 2-(bromomethyl)oxirane (27 mg, 0.195 mmol). The resulting mixture was heated at 90° C. for 3.5 h, cooled to rt and filtered. The filtrate was treated with methanol, stirred at rt for 2 h, then was then heated at 90° C. for 1 h. The mixture was concentrated under vacuum and purified by preparative HPLC to provide 7-(2-hydroxy-3-methoxypropoxy)-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 44-5, 4.7 mg, 13%). 1H NMR (400 MHz, methanol-d4) δ 7.83 (1H, d, J=7.9 Hz), 7.72 (1H, d, J=0.7 Hz), 7.46-7.52 (4H, m), 7.38-7.45 (1H, m), 7.04-7.12 (2H, m), 6.99 (1H, d, J=8.8 Hz), 6.70 (1H, dd, J=8.7, 2.3 Hz), 4.86 (2H, d, J=1.8 Hz), 4.03-4.22 (3H, m), 3.53-3.65 (2H, m), 3.42 (3H, s), 2.50 (3H, s), 1.93 (3H, s). Mass spectrum m/z 550.1 (M+H)+. Also isolated was 7-(3-(dimethylamino)-2-hydroxypropoxy)-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 44-6, 2.0 mg, 5%). Mass spectrum m/z 563.1 (M+H)+.

Workup

  1. temperatureThe resulting mixture was heated at 90° C. for 3.5 h
  2. temperaturecooled to rt
  3. filtrationfiltered
  4. additionThe filtrate was treated with methanol
  5. stirringstirred at rt for 2 h
  6. temperaturewas then heated at 90° C. for 1 h
  7. concentrationThe mixture was concentrated under vacuum
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-ce6e6861b31642dd8cfbaff745655531
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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