M-Phenylenediamine → N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]benzene-1,3-diamine

HRID 540101Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 540101
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.[C:26]1([NH2:33])[CH:31]=[CH:30][CH:29]=[C:28]([NH2:32])[CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[O:24]=[S:16]1(=[O:25])[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH2:19][N:13]([C:4]2[CH:3]=[C:2]([NH:32][C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([NH2:33])[CH:27]=3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=2)[CH2:14][CH2:15]1

Komponenten

7

Edukt 4

HCID 7935M-PhenylenediamineHCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Produkt 1

HCID 86691382N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]benzene-1,3-diamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (150 mg, 0.40 mmol, prepared in analogy to the one in Example 2-1), benzene-1,3-diamine (86 mg, 0.80 mmol), palladium acetate (18 mg, 0.04 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (50 mg, 0.04 mmol), potassium phosphate (169.6 mg, 0.8 mmol) and 1,4-dioxane (3 mL) in a 2-5 mL of process vial was heated at 140° C. under microwave irradiation for 1.5 hours. After being cooled to room temperature, the mixture was filtered and washed with ethyl acetate. The filtrate was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford the pure product as a solid. MS obsd. (ESI+) [(M+H)+] 445, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.31 (s, 1 H), 7.88 (dd, J=6.06, 1.52 Hz, 2 H), 7.63 (td, J=7.52, 1.14 Hz, 1 H), 7.54-7.46 (m, 1 H), 7.42-7.33 (m, 2 H), 7.33-7.27 (m, 1 H), 7.16 (t, J=7.83 Hz, 1 H), 6.52 (t, J=1.89 Hz, 1 H), 6.49-6.34 (m, 3 H), 5.23 (s, 2 H), 4.86 (s, 2 H), 3.60 (brs, 2 H), 2.38 (s, 3 H).

Aufarbeitung

  1. temperatureAfter being cooled to room temperature
  2. filtrationthe mixture was filtered
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-f20aa9189a604cb7a9bcab6117e174cc
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08871756B2

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