Methanesulfonyl chloride → 4-bromo-7-(methylsulfonamidomethyl)-9H-carbazole-1-carboxamide

HRID 1811181

Reaktionsgleichung

Reaktionsgleichung von HRID 1811181
[NH2:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([Br:19])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>CN(C=O)C.C1COCC1.C(Cl)Cl>[Br:19][C:8]1[C:7]2[C:6]3[C:14](=[CH:15][C:3]([CH2:2][NH:1][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:4][CH:5]=3)[NH:13][C:12]=2[C:11]([C:16]([NH2:18])=[O:17])=[CH:10][CH:9]=1

Komponenten

4

Edukt 2

HCID 31297Methanesulfonyl chlorideHCID 666063397-(aminomethyl)-4-bromo-9H-carbazole-1-carboxamide

Produkt 1

HCID 666064034-bromo-7-(methylsulfonamidomethyl)-9H-carbazole-1-carboxamideAusbeute 104,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 86642945dichloromethane tetrahydrofuran DMFLösungsmittel

Versuchsvorschrift

A suspension of 7-(aminomethyl)-4-bromo-9H-carbazole-1-carboxamide (Step 2 of Example 33-1, 100 mg, 0.314 mmol) and TEA (0.110 mL, 0.786 mmol) in DMF-THF-DCM (25:25:50, 6 mL) was treated dropwise with methanesulfonyl chloride (37 μL, 0.471 mmol) and the resulting mixture was stirred at rt for 3 h. The mixture was partitioned between NaHCO3 (aq) and EtOAc, and the organic phase was washed with brine, dried and concentrated to provide crude 4-bromo-7-(methylsulfonamidomethyl)-9H-carbazole-1-carboxamide as a yellow solid (130 mg, 88%). Without purification, using the procedure of Example 3-2, this material (25 mg, 0.063 mmol) and 6-fluoro-2-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)isoindolin-1-one (Intermediate 50-5, 27.8 mg, 0.076 mmol) were converted into 4-(3-(6-fluoro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-(methylsulfonamidomethyl)-9H-carbazole-1-carboxamide (22 mg, 58%). 1H NMR (400 MHz, DMSO-d6) δ 11.58 (1H, s), 8.20 (1H, br. s.), 8.03 (1H, d, J=7.9 Hz), 7.70-7.78 (2H, m), 7.45-7.67 (6H, m), 7.36 (1H, dd, J=7.7, 1.1 Hz), 7.00-7.07 (2H, m), 6.93-7.00 (1H, m), 4.86-5.04 (2H, m), 4.26 (2H, d, J=6.2 Hz), 2.87 (3H, s), 1.84 (3H, s). Mass spectrum m/z 557.1 (M+H)+.

Aufarbeitung

  1. customThe mixture was partitioned between NaHCO3 (aq) and EtOAc
  2. washthe organic phase was washed with brine
  3. customdried
  4. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-f81849e0d46c4c9da0fe8e8e8c032d97
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362065B2

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