Potassium Carbonate → HCID 59374997, compound

HRID 661950Notes

Reaction equation

HRID 661950 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(=O)([O-])[O-].[K+].[K+].Br[CH2:43][CH2:44][O:45][Si](C(C)(C)C)(C)C>CN(C=O)C>[OH:45][CH2:44][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 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 66606478HCID 66606478, compound

Product 1

HCID 59374997HCID 59374997, compoundYield 50.2%

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-bromoethoxy)(tert-butyl)dimethylsilane (62.2 mg, 0.260 mmol) and heated at 90° C. for 4 h. The mixture was filtered, the filtrate was treated with hydrogen chloride (4 M in dioxane, 1 mL) and the solution was stirred at rt overnight. The solution was concentrated under vacuum and the residue was purified by preparative HPLC to provide 7-(2-hydroxyethoxy)-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide as an off-white solid (16.5 mg, 45%). 1H NMR (400 MHz, DMSO-d6) δ 11.39 (1H, s), 8.17 (1H, br. s.), 7.94 (1 H, d, J=7.9 Hz), 7.53-7.65 (3H, m), 7.49 (3H, t, J=7.8 Hz), 7.27-7.39 (2H, m), 6.99 (1H, d, J=7.7 Hz), 6.92 (1H, d, J=8.8 Hz), 6.59 (1H, dd, J=8.8, 2.4 Hz), 4.75-4.98 (3H, m), 3.95-4.07 (2H, m), 3.69-3.80 (2H, m), 2.44 (3H, s). Mass spectrum m/z 506.0 (M+H)+.

Workup

  1. temperatureheated at 90° C. for 4 h
  2. filtrationThe mixture was filtered
  3. additionthe filtrate was treated with hydrogen chloride (4 M in dioxane, 1 mL)
  4. stirringthe solution was stirred at rt overnight
  5. concentrationThe solution was concentrated under vacuum
  6. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-550f8f67b79647aa847e50296e0cf8f4
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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