Hydrochloric Acid → HCID 178463549, Verbindung

HRID 510916Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 510916
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11](C(OCC)C)[CH:12]=2)[C:5]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)=[C:4]([CH:26]([NH2:28])[CH3:27])[CH:3]=1.Br[C:30]1[N:38]=[CH:37][N:36]=[C:35]2[C:31]=1[N:32]=[CH:33][N:34]2C1CCCCO1.C(N(CC)C(C)C)(C)C.Cl.O>C(O)C.CO>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:12]=[N:11][NH:10][CH:9]=2)[C:5]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)=[C:4]([CH:26]([NH:28][C:30]2[N:38]=[CH:37][N:36]=[C:35]3[C:31]=2[N:32]=[CH:33][NH:34]3)[CH3:27])[CH:3]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 81531DiisopropylethylamineHCID 583686166-Bromo-9-(tetrahydro-2H-pyran-2-YL)-9H-purineHCID 679691831-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanamine

Produkt 1

HCID 178463549HCID 178463549, VerbindungAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A solution of 1-{4-chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3′,5′-difluorobiphenyl-2-yl}ethanamine (60 mg, 0.15 mmol), 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (63 mg, 0.22 mmol, from Example 108, Step 1), and N,N-diisopropylethylamine (77 μL, 0.44 mmol) in ethanol (2.8 mL) was heated in the microwave at 130° C. for 30 minutes. Alternatively, this reaction can be heated at 90° C. overnight on the benchtop. The reaction mixture was cooled to room temperature, treated with 6 M Hydrogen chloride in water (0.49 mL, 3.0 mmol), and stirred for 30 minutes. The reaction mixture was diluted slightly with methanol, filtered, and directly purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (29 mg, 43%). LCMS for C22H17ClF2N7 (M+H)+: m/z=452.1. Found: 452.0; 1H NMR (300 MHz, DMSO-d6): δ 12.8 (br s, 1H), 8.32-8.23 (m, 1H), 8.11 (s, 1H), 8.06 (s, 1H), 7.65 (s, 1H), 7.46 (s, 1H), 7.36-7.23 (m, 3H), 7.09-7.01 (m, 1H), 6.96 (d, J=8.5 Hz, 1H), 5.09-4.96 (m, 1H), 1.34 (d, J=6.7 Hz, 3H).

Aufarbeitung

  1. customAlternatively, this reaction
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. customdirectly purified via preparative LCMS (XBridge C18 column
  5. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-4a3e0c9f292846f7ba9aa5d56b5f2b12
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096600B2

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