Sodium Carbonate → HCID 178488202, Verbindung

HRID 897603Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 897603
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:28]=[C:29](B(O)O)[CH:30]=[CH:31][C:32]=1[N:33]([CH3:44])[C:34](=[O:43])[CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.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:29]3[CH:30]=[CH:31][C:32]([N:33]([CH3:44])[C:34](=[O:43])[CH2:35][CH2:36][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)=[C:27]([O:26][CH3:25])[CH:28]=3)[C:10]=12

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 223472033-Methoxy-4-[methyl(3-phenylpropanoyl)amino]phenylboronic acidHCID 178481014HCID 178481014, Verbindung

Produkt 1

HCID 178488202HCID 178488202, VerbindungAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A solution of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.293 g, 0.664 mmol) in ethylene glycol dimethyl ether (10 mL) was treated with 3-methoxy-4-[methyl(3-phenylpropanoyl)amino]phenylboronic acid (0.290 g, 0.730 mmol), tetrakis(triphenylphosphine)palladium (0.046 g, 0.040 mmol), and a solution of sodium carbonate (0.169 g, 1.59 mmol) in water (5 mL). The reaction mixture was stirred over night at 85° C. under a nitrogen atmosphere. The solvent was removed under reduced pressure, and ethyl acetate was added to the aqueous layer. The layers were partitioned, and the aqueous layer was extracted with ethyl acetate (150 mL). The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel using 4% methanol in dichloromethane, 8% methanol in dichloromethane, and then 12% methanol in dichloromethane as eluent. A second column using a Supelco flash chromatography silica gel column using 30% methanol in dichloromethane afforded 0.037 g (10%) of cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-N1-methyl-3-phenylpropanamide. 1H NMR (CDCl3, 400 MHz) δ 8.374 (s, 1H), 7.315-7.312 (m, 1H), 7.285-7.213 (m, 3H), 7.174-7.087 (m, 4H), 5.795 (br. s., 2H), 4.965-4.922 (m, 1H), 3.892 (s, 3H), 3.213 (s, 3H), 2.948-2.918 (m, 2H), 2.667 (m, 6H), 2.455-2.349 (m, 10H), 2.25-2.15 (m, 2H), 1.867-1.845 (m, 2H), 1.718-1.710 (m, 2H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 4.947 min (98%).

Aufarbeitung

  1. customThe solvent was removed under reduced pressure, and ethyl acetate
  2. additionwas added to the aqueous layer
  3. customThe layers were partitioned
  4. extractionthe aqueous layer was extracted with ethyl acetate (150 mL)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by flash chromatography on silica gel using 4% methanol in dichloromethane, 8% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-f10861de1bea421fb6026b01df90ee0b
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921763B2

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