Sodium Carbonate → HCID 67959573, Verbindung

HRID 1529386Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529386
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[C:17]1[N:22]=[C:21]([O:23][C@H:24]2[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:28][C:25]32[CH2:27][CH2:26]3)[CH:20]=[N:19][CH:18]=1.[CH:39]1([NH:42][C:43]([C:45]2[CH:46]=[C:47](B(O)O)[CH:48]=[CH:49][CH:50]=2)=[O:44])[CH2:41][CH2:40]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:39]1([NH:42][C:43]([C:45]2[CH:50]=[C:49]([C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[N:6]=[C:5]4[C:17]3[N:22]=[C:21]([O:23][C@H:24]4[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:29][CH2:28][C:25]54[CH2:27][CH2:26]5)[CH:20]=[N:19][CH:18]=3)[CH:48]=[CH:47][CH:46]=2)=[O:44])[CH2:40][CH2:41]1

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 38742473-(Cyclopropylaminocarbonyl)phenylboronic acidHCID 67959732HCID 67959732, Verbindung

Produkt 1

HCID 67959573HCID 67959573, VerbindungAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A glass microwave reaction vessel was charged with (4R)-tert-butyl 4-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (115 mg, 0.20 mmol), 3-(cyclopropylcarbamoyl)phenylboronic acid (81 mg, 0.39 mmol), PdCl2(PPh3)2 (11 mg, 0.016 mmol) and Na2CO3 (104 mg, 0.98 mmol) in dioxane (0.8 mL) and water (0.2 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 20 min. The layers were separated and the organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-75% EtOAc in hexanes, to provide (4R)-tert-butyl 4-(6-(5-(3-(cyclopropylcarbamoyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (107 mg, 0.16 mmol, 82% yield) as a clear, colorless oil. MS (ESI, pos. ion) m/z: 665.3 (M+1).

Aufarbeitung

  1. customA glass microwave reaction vessel
  2. customThe layers were separated
  3. dry with materialthe organic phase was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-75% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-f2d09b313fd54372883a61908200bd3e
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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