1,2-Dichloroethane → 3-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

HRID 2410670Notes

Reaction equation

HRID 2410670 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([C:15](=[O:17])[NH2:16])[CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([C:18](O)=[O:19])[CH:7]=[CH:6][C:5]2=1.C(Cl)CCl.O.ON1C2C=CC=CC=2N=N1.[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[Br:1][C:2]1[CH:14]=[C:13]([C:15]([NH2:16])=[O:17])[C:12]2[NH:11][C:10]3[C:5]([C:4]=2[CH:3]=1)=[CH:6][CH:7]=[C:8]([C:18]([N:40]1[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]1)=[O:19])[CH:9]=3

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 27960291-Hydroxybenzotriazole hydrateHCID 666048126-bromo-8-carbamoyl-9H-carbazole-2-carboxylic acid

Product 1

HCID 666051623-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

To a suspension of 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylic acid (8.47 g, 8.64 mmol), EDC (1.657 g, 8.64 mmol), and 1-hydroxybenzotriazole hydrate (1.324 g, 8.64 mmol) in THF/CH2Cl2 (5/1) (40 mL) was added 1-methylpiperazine (3.84 mL, 34.6 mmol). The reaction mixture turned into a dark pink suspension. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated and partitioned between ethyl acetate and water/sat. NaHCO3. The aqueous phase was re-extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and concentrated to afford the crude product as a dark pink solid, which was purified by silica gel column chromatography (CH2Cl2/2M NH3 in MeOH=100/5-100/7). The product obtained was suspended in ethyl acetate and colorless solid was collected by filtration and air-dried to give 1.78 G of 3-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide. MS (ESI) m/z 415.1 (M+H). 1H NMR (DMSO-d6) δ ppm 11.68 (s, 1H) 8.60 (d, J=1.76 Hz, 1H) 8.28 (br. s., 1H 8.24 (d, J=8.13 Hz, 1H), 8.16 (d, J=1.76 Hz, 1H) 7.75 (s, 1H) 7.64 (br. s., 1H) 7.14-7.22 (m, 1H) 3.34-3.75 (m, 4H) 2.24-2.44 (m, 4H) 2.20 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between ethyl acetate and water/
  3. extractionThe aqueous phase was re-extracted with ethyl acetate
  4. washThe organic phase was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto afford the crude product as a dark pink solid, which
  8. customwas purified by silica gel column chromatography (CH2Cl2/2M NH3 in MeOH=100/5-100/7)
  9. customThe product obtained
  10. filtrationcolorless solid was collected by filtration
  11. customair-dried

Sources & evidence

ORD record
ord-5fc0b365e01a4c27969a5790f0aa113a
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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