Sodium hydride → HCID 59375166, Verbindung

HRID 1811119Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1811119
[NH2:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.Br[CH2:46][CH2:47][CH2:48][C:49](Cl)=[O:50].[H-].[Na+]>C1COCC1.C(Cl)Cl.CCOC(C)=O.O>[CH3:35][C:20]1[C:21]([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]2=[O:34])=[CH:22][CH:23]=[CH:24][C:19]=1[C:8]1[C:7]2[C:6]3[C:14](=[CH:15][C:3]([CH2:2][N:1]4[CH2:46][CH2:47][CH2:48][C:49]4=[O:50])=[CH:4][CH:5]=3)[NH:13][C:12]=2[C:11]([C:16]([NH2:18])=[O:17])=[CH:10][CH:9]=1

Komponenten

9

Edukt 4

HCID 24758Sodium hydrideHCID 702254-Bromobutyryl chlorideHCID 81531DiisopropylethylamineHCID 59375043HCID 59375043, Verbindung

Produkt 1

HCID 59375166HCID 59375166, VerbindungAusbeute 4,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A solution of 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 80 mg, 0.087 mmol) in THF (3 mL) was treated with DIEA (0.030 mL, 0.174 mmol) and a solution of 4-bromobutanoyl chloride (10 μL, 0.087 mmol) in DCM (1 mL) and the mixture was stirred at rt for 35 min. The reaction mixture was diluted with EtOAc, washed with NaHCO3 (aq) and brine, and dried and concentrated. The residue was dissolved in THF (6 mL) and treated with sodium hydride (60% oil dispersion, 24.32 mg, 0.608 mmol). The resulting mixture was stirred at 50° C. for 2 h, then was diluted with water and extracted with EtOAc. The organic phase was dried and concentrated, and the residue was purified by preparative HPLC to provide 4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-7-((2-oxopyrrolidin-1-yl)methyl)-9H-carbazole-1-carboxamide as a white solid (2 mg, 3%). 1H NMR (400 MHz, DMSO-d6) δ 11.44 (1 H, s), 8.11 (1 H, br. s.), 7.95 (1 H, d, J=7.9 Hz), 7.73 (1 H, d, J=7.5 Hz), 7.62 (2 H, d, J=3.7 Hz), 7.46-7.57 (3 H, m), 7.42 (2 H, t, J=7.7 Hz), 7.23-7.29 (1 H, m), 6.90-6.99 (2 H, m), 6.74 (1 H, dd, J=8.1, 1.5 Hz), 4.79-5.00 (2 H, m), 4.25-4.51 (2 H, m), 3.11-3.22 (2 H, m), 2.19-2.29 (2 H, m), 1.80-1.93 (2 H, m), 1.77 (3 H, s). Mass spectrum m/z 529.2 (M+H)+.

Aufarbeitung

  1. washwashed with NaHCO3 (aq) and brine
  2. customdried
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in THF (6 mL)
  5. extractionextracted with EtOAc
  6. customThe organic phase was dried
  7. concentrationconcentrated
  8. customthe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-10bb025aeee44bfdb0041b21213f06db
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362065B2

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