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

HRID 661902

Reaktionsgleichung

Reaktionsgleichung von HRID 661902
[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[NH2:16])=[C:11]2[C:3]=1[C:4]1[CH:5]=[CH:6][C:7]([C:18](O)=[O:19])=[CH:8][C:9]=1[NH:10]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:35][N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1>C1COCC1.C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[C:3]2[C:4]3[C:9](=[CH:8][C:7]([C:18]([N:39]4[CH2:40][CH2:41][N:36]([CH3:35])[CH2:37][CH2:38]4)=[O:19])=[CH:6][CH:5]=3)[NH:10][C:11]=2[C:12]([C:15]([NH2:16])=[O:17])=[CH:13][CH:14]=1

Komponenten

6

Edukt 4

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 593750825-bromo-8-carbamoyl-9H-carbazole-2-carboxylic acid2×

Produkt 1

HCID 468335224-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamideAusbeute 76,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 86642945dichloromethane tetrahydrofuran DMFLösungsmittel

Versuchsvorschrift

A suspension of 5-bromo-8-carbamoyl-9H-carbazole-2-carboxylic acid (Intermediate 49-1, 1.84 g, 4.97 mmol), EDC (1.334 g, 6.96 mmol), and HOBT (1.066 g, 6.96 mmol) in THF-DCM-DMF (4:1:1) (124 mL) was treated with 1-methylpiperazine (1.656 mL, 14.91 mmol) and the mixture was stirred at rt for 3 days. The mixture was concentrated and the residue was partitioned between DCM and NaHCO3 (aq). The organic phase was washed with brine, dried and concentrated to afford an oil. This was purified by column chromatography (DCM-2 M methanolic ammonia, 100:0 to 95:5 to 92.5:7.5). The resulting solid was suspended in EtOAc, collected by filtration and dried to provide 4-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (1.57 g, 76%). 1H NMR (400 MHz, DMSO-d6) δ 11.83 (s, 1H) 8.57 (d, J=8.13 Hz, 1H) 8.20 (br. s., 1H) 7.84 (d, J=8.35 Hz, 1H) 7.79 (s, 1H) 7.56 (br. s., 1H) 7.42 (d, J=8.13 Hz, 1H) 7.22 (d, J=8.13 Hz, 1H) 3.30-3.70 (m, 4H) 2.19-2.39 (m, 4H) 2.16 (s, 3H). Mass spectrum m/z 415, 417 (M+H)+.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between DCM and NaHCO3 (aq)
  3. washThe organic phase was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customto afford an oil
  7. customThis was purified by column chromatography (DCM-2 M methanolic ammonia, 100:0 to 95:5 to 92.5:7.5)
  8. filtrationcollected by filtration
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-8523230392b840b5b5de5c2e8b7a95e6
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084620B2

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