Methanesulfonyl chloride → HCID 59374982, Verbindung

HRID 1811118Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1811118
[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.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C1COCC1>[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][NH:1][S:37]([CH3:36])(=[O:39])=[O:38])=[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 59375043HCID 59375043, Verbindung

Produkt 1

HCID 59374982HCID 59374982, VerbindungAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 60 mg, 0.065 mmol) and TEA (23 μL, 0.163 mmol) in THF (1.3 mL) was treated with methanesulfonyl chloride (5.6 μL, 0.072 mmol) and the mixture was stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC. The appropriate effluent fractions were concentrated and partitioned between EtOAc and NaHCO3 (aq). The organic phase was dried and concentrated, and the residue was purified further by column chromatography (eluting with a gradient from 40:60 hexane-EtOAc to EtOAc) to provide 4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-7-(methylsulfonamidomethyl)-9H-carbazole-1-carboxamide as an off-white solid (7 mg, 18%). 1H NMR (400 MHz, DMSO-d6) δ 11.57 (1 H, s), 8.19 (1 H, br. s.), 8.02 (1 H, d, J=7.7 Hz), 7.81 (1 H, d, J=7.7 Hz), 7.73 (1 H, s), 7.69 (2 H, d, J=3.7 Hz), 7.61-7.65 (1 H, m), 7.54-7.61 (2 H, m), 7.51 (2 H, t, J=7.7 Hz), 7.35 (1 H, dd, J=7.5, 1.1 Hz), 7.00-7.08 (2 H, m), 6.93-6.99 (1 H, m), 4.88-5.05 (2 H, m), 4.26 (2 H, d, J=5.9 Hz), 2.87 (3 H, s), 1.84 (3 H, s). Mass spectrum m/z 539.2 (M+H)+.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC
  3. concentrationThe appropriate effluent fractions were concentrated
  4. custompartitioned between EtOAc and NaHCO3 (aq)
  5. customThe organic phase was dried
  6. concentrationconcentrated
  7. customthe residue was purified further by column chromatography (
  8. washeluting with a gradient from 40:60 hexane-EtOAc to EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-3ee6e3588db9466abfaadd08e2904f07
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362065B2

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