1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6,6-dimethyl-4-(2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl)-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

HRID 552234Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 552234
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[CH2:20][N:19]3[CH2:26][CH:27]([NH2:30])[CH2:28][CH3:29])=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.[CH3:31][C:32]1[N:40]=[CH:39][CH:38]=[CH:37][C:33]=1[C:34](O)=[O:35].CCN=C=NCCCN(C)C>N1C=CC=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[CH2:23][O:22][C:21]([CH3:24])([CH3:25])[CH2:20][N:19]3[CH2:26][CH:27]([NH:30][C:34]([C:33]3[C:32]([CH3:31])=[N:40][CH:39]=[CH:38][CH:37]=3)=[O:35])[CH2:28][CH3:29])=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1

Komponenten

6

Edukt 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 6433732-Methylnicotinic acidHCID 671644174-(2-Amino-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

Produkt 1

HCID 671645916,6-dimethyl-4-(2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl)-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amideAusbeute 80,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 1049PyridineLösungsmittel

Versuchsvorschrift

To a solution of 4-(2-amino-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide (100 mg, 0.233 mmol) in pyridine (4 mL) was added 2-methyl-nicotinic acid (38.4 mg, 0.280 mmol) and EDCI (71.5 mg, 0.373 mmol). The solution was stirred overnight at room temperature, then diluted with water (5 mL). The mixture was poured into a separatory funnel and diluted further with water (20 mL). The mixture was extracted with EtOAc (2×20 mL), then the combined organic layers were washed with brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to yield a yellow-brown oil which was purified via column chromatography. The resulting yellow solid was dissolved in methanol (2 mL) and HCl in Et2O (2M, 2 mL) was added. The mixture was stirred for 5 minutes, then concentrated to yield 103 mg of 6,6-dimethyl-4-{2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide (71% yield). 1H-NMR (DMSO-d6, 300 MHz) δ 13.31 (br s, 1); 11.41 (br s, 1); 11.14 (br s, 1); 9.44 (s, 1); 8.85 (d, 1); 8.73-8.64 (m, 3); 8.52 (s, 1); 8.32 (s, 1); 7.72 (s, 1); 4.64-3.55 (m, 6); 3.24-3.06 (m, 1); 2.95-2.81 (m, 1); 2.71 (s, 3); 1.89-1.74 (m, 1); 1.55-1.41 (m, 1); 1.32 (s, 3); 1.23 (s, 3); 0.93 (t, 3). NH4OAc standard conditions. DAD Rf=1.66 min. M+H=549.

Aufarbeitung

  1. additionThe mixture was poured into a separatory funnel
  2. extractionThe mixture was extracted with EtOAc (2×20 mL)
  3. washthe combined organic layers were washed with brine
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a yellow-brown oil which
  8. customwas purified via column chromatography
  9. dissolutionThe resulting yellow solid was dissolved in methanol (2 mL)
  10. additionHCl in Et2O (2M, 2 mL) was added
  11. stirringThe mixture was stirred for 5 minutes
  12. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-3b42aa81a5de438f88b8220350044e63
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07951801B2

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