Potassium Carbonate → HCID 57521147, Verbindung

HRID 525102

Reaktionsgleichung

Reaktionsgleichung von HRID 525102
[CH3:1][NH:2][CH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[N:11]=[CH:12][N:13]=[C:14]3[C:21]=2[C:20]2[CH2:19][CH2:18][CH2:17][C:16]=2[S:15]3)[CH2:5][CH2:4]1.Cl[CH2:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:25].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][N:2]([CH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[N:11]=[CH:12][N:13]=[C:14]3[C:21]=2[C:20]2[CH2:19][CH2:18][CH2:17][C:16]=2[S:15]3)[CH2:5][CH2:4]1)[CH2:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:25]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 2223122-Chloro-1-piperidine-1-yl-ethanoneHCID 575202421-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]cyclohexane-1,4-diamine

Produkt 1

HCID 57521147HCID 57521147, VerbindungAusbeute 14,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Note: For the preparation of the starting material compound 1, see Example 147. To a solution of 1-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]cyclohexane-1,4-diamine (90 mg, 0.30 mmol, 1.00 equiv) in DMF (10 mL) was added 2-chloro-1-(piperidin-1-yl)ethan-1-one (72 mg, 0.45 mmol, 1.50 equiv) and potassium carbonate (83 mg, 0.60 mmol, 2.00 equiv) at room temperature under nitrogen. The resulting solution was stirred overnight at ambient temperature. After completion of the reaction, the solids were removed by filtration and the filtrate was concentrated under vacuum. The crude product (100 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH4HCO3 and CH3CN (7.0% CH3CN up to 55.0% in 19 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired 2-[methyl[4-([7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]amino)cyclohexyl]amino]-1-(piperidin-1-yl)ethan-1-one (18.4 mg) as a white solid. MS (ES, m/z): 428 (M+H+); 1H NMR (400 MHz, CD3OD): δ 8.23 (s, 1H), 4.08-4.09 (m, 1H), 3.54-3.59 (m, 4H), 3.39 (s, 2H), 3.08 (t, 2H, J=6.8 Hz), 2.99 (t, 2H, J=6.8 Hz), 2.54-2.59 (m, 3H), 2.34 (s, 3H), 2.16-2.19 (m, 2H), 1.94-1.97 (m, 2H), 1.45-1.70 (m, 10H).

Aufarbeitung

  1. customAfter completion of the reaction
  2. customthe solids were removed by filtration
  3. concentrationthe filtrate was concentrated under vacuum
  4. customThe crude product (100 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  5. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (7.0% CH3CN up to 55.0% in 19 min)
  6. customThe product-containing fractions were collected
  7. custompartially evaporated
  8. customto remove water and CH3CN under reduced pressure
  9. waitThe residue was lyophilized overnight

Quellen und Nachweise

ORD-Eintrag
ord-34e0a01e795145a39ae412630af67056
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340554B2

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