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

HRID 1811083

反応式

HRID 1811083 の反応式
[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

参加物

6

反応物 4

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

生成物 1

HCID 468335224-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide収率 76.1%

試薬・触媒・溶媒 1

HCID 86642945dichloromethane tetrahydrofuran DMF溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-691362b625a443439bceff99dec500ac
出典データセット
uspto-grants-2013_01
特許番号
US08362065B2

関連ノート

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