Sodium Carbonate → HCID 178488203, Verbindung

HRID 898061

Reaktionsgleichung

Reaktionsgleichung von HRID 898061
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.[CH3:25][O:26][C:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[CH:29][C:28]=1[NH:42][C:43]([C:45]1[N:46]([CH3:54])[C:47]2[C:52]([CH:53]=1)=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:44].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:31]3[CH:30]=[CH:29][C:28]([NH:42][C:43]([C:45]4[N:46]([CH3:54])[C:47]5[C:52]([CH:53]=4)=[CH:51][CH:50]=[CH:49][CH:48]=5)=[O:44])=[C:27]([O:26][CH3:25])[CH:32]=3)[C:10]=12

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamideHCID 178481015HCID 178481015, Verbindung

Produkt 1

HCID 178488203HCID 178488203, VerbindungAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A suspension of trans-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.100 g, 0.227 mmol) in ethylene glycol dimethyl ether (8 mL) was treated with N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (0.097 g, 0.238 mmol), tetrakis(triphenylphosphine)palladium (0.016 g, 0.014 mmol), and a solution of sodium carbonate (0.057 g, 0.538 mmol) in water (4 mL). The reaction mixture was stirred for 21.5 h at 80° C. The precipitate was filtered, and the organic layer was evaporated under reduced pressure. Dichloromethane (15 mL) was added and the layers were partitioned. The aqueous layer was extracted with dichloromethane (200 mL). The combined organic layers were dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a 10% methanol in dichloromethane to 50% methanol in dichloromethane step gradient on Sq 16× ISCO CombiFlash. The column afforded 0.083 g (68%) of trans-N2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide. 1H NMR (d6-DMSO) δ 9.4316 (s, 1H), 8.2427 (s, 1H), 8.1207-8.1003 (d, 1H, J=8.16 Hz), 7.7173-7.6974 (d, 1H, J=7.96 Hz), 7.5979-7.5769 (d, 1H, J=8.4 Hz), 7.3507-7.2758 (m, 4H), 7.1695-7.1321 (t, 1H), 4.6893-4.6324 (m, 1H), 4.0400 (s, 3H), 3.9571 (s, 3H), 2.5 (m, 3H), 2.4055-2.3279 (m, 5H), 2.1606 (s, 3H), 2.1094-1.9367 (m, 6H), 1.5214-1.4624 (m, 2H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium Acetate in Water to 95% Acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 2.12 min (100%), M+ 594.3.

Aufarbeitung

  1. filtrationThe precipitate was filtered
  2. customthe organic layer was evaporated under reduced pressure
  3. additionDichloromethane (15 mL) was added
  4. customthe layers were partitioned
  5. extractionThe aqueous layer was extracted with dichloromethane (200 mL)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude material was purified by flash chromatography on silica gel using a 10% methanol in dichloromethane to 50% methanol in dichloromethane step gradient on Sq 16× ISCO CombiFlash

Quellen und Nachweise

ORD-Eintrag
ord-760a6899b8154f179da06a92054da660
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921763B2

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