Triethylamine → HCID 178488221, Verbindung

HRID 432247

Reaktionsgleichung

Reaktionsgleichung von HRID 432247
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].C(N(CC)CC)C.[C:40](Cl)(=[O:49])[CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>ClCCl>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:40](=[O:49])[CH2:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 64801Benzenepropanoyl chloride2×HCID 178488197HCID 178488197, Verbindung

Produkt 1

HCID 178488221HCID 178488221, VerbindungAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of cis-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (75 mg, 0.17 mmol) and triethylamine (34 mg, 0.34 mmol) in dichloromethane (2.5 ml) was added hydrocinnamoyl chloride (34 mg, 0.20 mmol) in dichloromethane (0.5 ml) dropwise. The solution was stirred at room temperature for 48 hr and a further equivalent of hydrocinnamoyl chloride was then added. The reaction mixture was stirred for a further 24 hr. The resulting mixture was partitioned between dichloromethane (4 ml) and 2N NaOH (1.5 ml) and passed through an Empore extraction cartridge. Evaporation of the solvent gave an oily solid which was purified by silica gel chromatography using 10-20% MeOH/dichloromethane to give cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-3-phenylpropanamide (12 mg, 13%). 1H NMR (CDCl3): δ H 8.55 (1H, d), 8.36 (1H, s), 7.75 (1H, s), 7.25 (7H, m), 5.51 (2H, bs), 4.91 (1H, m), 3.92 (3H, s), 3.09 (2H, m), 2.76 (2H, m), 2.34-2.59 (9H, m), 2.29 (3H, s), 2.16 (2H, m), 1.85 (4H, m), 1.66 (2H, m). LCMS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min.(B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 3.5 mL/min.) Rt=1.92 mins, MH+=569.6.

Aufarbeitung

  1. stirringThe reaction mixture was stirred for a further 24 hr
  2. customThe resulting mixture was partitioned between dichloromethane (4 ml) and 2N NaOH (1.5 ml)
  3. extractionpassed through an Empore extraction cartridge
  4. customEvaporation of the solvent
  5. customgave an oily solid which
  6. customwas purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-9759f9ae41374d3d93ac518cb7fe753d
Quelldatensatz
uspto-grants-2003_12
Patentnummer
US06660744B1

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