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

HRID 523232Notes

Reaction equation

HRID 523232 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][C:3]=1I.[CH3:23][N:24](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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[C:23]#[N:24]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 1177606584-bromo-7-(2-hydroxypropan-2-yl)-3-iodo-9H-carbazole-1-carboxamide

Product 1

HCID 1177606764-bromo-3-cyano-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamideYield 83%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 4-bromo-7-(2-hydroxypropan-2-yl)-3-iodo-9H -carbazole-1-carboxamide (0.609 g, 1.29 mmol) and zinc cyanide (0.076 g, 0.644 mmol) in DMF (7 mL) was subjected to three evacuate-fill cycles with nitrogen. The mixture was treated with tetrakis(triphenylphosphine)palladium (0.074 g, 0.064 mmol) and heated overnight at 95° C. The cooled mixture was diluted with EtOAc, washed twice with 10% aqueous LiCl, then with brine. The aqueous layers were extracted with EtOAc. The combined organic layers were dried and concentrated. The residue was triturated and sonicated with DCM and the precipitate was collected by filtration to give 4-bromo-3-cyano-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide as a pale yellow solid (0.400 g, 83% yield). Mass spectrum m/z 372, 374 (M+H—H2O)+. 1H NMR (500 MHz, DMSO-d6) δ 12.12 (s, 1H), 8.55 (d, J=8.6 Hz, 1H), 8.38 (s, 1H), 8.31 (br. s., 1H), 8.03 (s, 1H), 7.74 (br. s., 1H), 7.49 (dd, J=8.6, 1.1 Hz, 1H), and 1.52 (s, 6H).

Workup

  1. customevacuate-fill cycles with nitrogen
  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 triturated
  7. customsonicated with DCM
  8. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-2f6aa1d8b62d444cabecc53f20d4c986
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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