4-Toluenesulfonyl chloride → HCID 57969035, Verbindung

HRID 1664450Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1664450
[NH2:1][CH2:2][C:3]1[CH:19]=[CH:18][C:6]([O:7][C:8]2[CH:17]=[CH:16][C:11]3[B:12]([OH:15])[O:13][CH2:14][C:10]=3[CH:9]=2)=[CH:5][CH:4]=1.[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1.CCN(CC)CC>C(Cl)Cl>[OH:15][B:12]1[C:11]2[CH:16]=[CH:17][C:8]([O:7][C:6]3[CH:18]=[CH:19][C:3]([CH2:2][NH:1][S:27]([C:24]4[CH:25]=[CH:26][C:21]([CH3:20])=[CH:22][CH:23]=4)(=[O:29])=[O:28])=[CH:4][CH:5]=3)=[CH:9][C:10]=2[CH2:14][O:13]1

Komponenten

5

Edukt 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 57968923Crisaborole intermediate

Produkt 1

HCID 57969035HCID 57969035, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a 20 mL scintillation vial containing 5-(4-aminomethyl-phenoxy)-3H-benzo[c][1,2]oxaborol-1-ol (144 mg, 0.56 mmol, 1.1 eq.), 4-methyl-benzenesulfonyl chloride (118.4 mg, 0.62 mmol, 1.1 eq.) in DCM (10.0 mL) was added Et3N (160 μL, 1.12 mmol, 2.0 eq.) drop wise. The mixture was stirred at room temperature overnight. The mixture was carefully treated with aqu. NH4Cl (10 mL) and the layers were separated. The aqueous was extracted with DCM (2×5 mL), combined organic phase was washed with H2O (10 mL), brine (10 mL), dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with EtOAc/Heptanes (0:100 to 80:20) to give N-[4-(1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-benzyl]-4-methyl-benzenesulfonamide as a white solid. LCMS (m/z) 432 (M+23); 1H NMR (400 MHz, DMSO-d) δ ppm 1H NMR (DMSO-d6) δ: 9.11 (s, 1H), 8.08 (t, J=6.3 Hz, 1H), 7.65-7.74 (m, 3H), 7.38 (d, J=8.0 Hz, 2H), 7.23-7.31 (m, J=8.6 Hz, 2H), 6.95-7.00 (m, 2H), 6.89-6.95 (m, 2H), 4.92 (s, 2H), 3.95 (d, J=6.3 Hz, 2H), 2.38 (s, 3H).

Aufarbeitung

  1. additionThe mixture was carefully treated with aqu
  2. customNH4Cl (10 mL) and the layers were separated
  3. extractionThe aqueous was extracted with DCM (2×5 mL)
  4. washwas washed with H2O (10 mL), brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. washeluting with EtOAc/Heptanes (0:100 to 80:20)

Quellen und Nachweise

ORD-Eintrag
ord-6ce210bdbacf432a9bd5e5a038821e54
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08039450B2

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