Pyridine → 4-bromo-7-(2-hydroxypropan-2-yl)-3-iodo-9H-carbazole-1-carboxamide

HRID 523231Notes

Reaction equation

HRID 523231 reaction equation
[Br:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([C:15]([OH:18])([CH3:17])[CH3:16])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:19]([NH2:21])=[O:20])=[CH:4][CH:3]=1.[I:22]N1C(=O)CCC1=O.N1C=CC=CC=1>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([C:15]([OH:18])([CH3:17])[CH3:16])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:19]([NH2:21])=[O:20])=[CH:4][C:3]=1[I:22]

Participants

6

Reactant 3

HCID 1049PyridineHCID 120273N-IodosuccinimideHCID 66605841HCID 66605841, compound

Product 1

HCID 1177606584-bromo-7-(2-hydroxypropan-2-yl)-3-iodo-9H-carbazole-1-carboxamideYield 23%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-bromo-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide [synthesized according to the procedure described in U.S. Pat. No. 8,084,620, Example 73-2] (2.00 g, 5.76 mmol), N-iodosuccinimide (1.69 g, 7.49 mmol), and pyridine (1.9 mL, 23.0 mmol) in DMF (20 mL) was heated at 65° C. for 2 days. The cooled mixture was diluted with EtOAc, washed twice with 10% aqueous LiCl and then with brine. The aqueous layers were extracted with EtOAc. The combined organic layers were dried and concentrated, and the residue was purified by column chromatography on silica gel, eluting with EtOAc-hexanes (gradient from 50%-65%), to provide 4-bromo-7-(2-hydroxypropan-2-yl)-3-iodo-9H-carbazole-1-carboxamide as a yellow solid (0.609 g, 23% yield). Mass spectrum m/z 473, 475 (M+H—H2O)+. 1H NMR (500 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.49 (d, J=8.6 Hz, 1H), 8.38 (s, 1H), 8.26 (br. s., 1H), 7.94 (d, J=1.1 Hz, 1H), 7.58 (br. s., 1H), 7.40 (dd, J=8.6, 1.4 Hz, 1H), 5.09 (s, 1H), and 1.51 (s, 6H).

Workup

  1. customsynthesized
  2. washwashed twice with 10% aqueous LiCl
  3. extractionThe aqueous layers were extracted with EtOAc
  4. customThe combined organic layers were dried
  5. concentrationconcentrated
  6. customthe residue was purified by column chromatography on silica gel
  7. washeluting with EtOAc-hexanes (gradient from 50%-65%)

Sources & evidence

ORD record
ord-1251fd275c224e63a2c7c0dff2a93411
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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