Sodium Carbonate → 5-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

HRID 605938Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 605938
CN1CCN(C2C=CC(NC3C4N(N=CN=4)C(C4C=C(C(N)=O)SC=4)=CN=3)=CC=2)CC1.Br[C:33]1[N:38]2[N:39]=[CH:40][N:41]=[C:37]2[C:36]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[CH:45][CH:44]=2)=[N:35][CH:34]=1.CC1(C)C(C)(C)OB([C:66]2[CH:67]=[C:68]3[C:72](=[CH:73][CH:74]=2)[C:71](=[O:75])[NH:70][CH2:69]3)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[O:55]1[CH2:56][CH2:57][N:52]([CH2:51][CH2:50][O:49][C:46]2[CH:47]=[CH:48][C:43]([NH:42][C:36]3[C:37]4[N:38]([N:39]=[CH:40][N:41]=4)[C:33]([C:66]4[CH:67]=[C:68]5[C:72](=[CH:73][CH:74]=4)[C:71](=[O:75])[NH:70][CH2:69]5)=[CH:34][N:35]=3)=[CH:44][CH:45]=2)[CH2:53][CH2:54]1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 57590052(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine

Produkt 1

HCID 248882625-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

This compound may be prepared using the methods as described for Compound 6, step 4, using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine (80 mg, 0.19 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (74 mg, 0.29 mmol), and Pd(PPh3)4 (55 mg, 0.047 mmol) in 1.5M Na2CO3 (1.02 mL, 1.53 mmol) and dioxane (3 mL). The reaction mixture is purified by silica gel column chromatography eluting with DCM and a 97:3 mixture DCM:NH3 (7M in MeOH). After trituration using diethyl ether, the title compound is isolated as a solid (61.9 mg, 69%). Conversion of the material into the mesylate salt, using 1M methanesulfonic acid (0.134 mL) in MeOH, affords the title compound (57.1 mg). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.40 (3H, s, MsOH), 3.25-3.38 (2H, m), 3.60-3.78 (4H, m), 3.84 (2H, t), 4.09 (2H, d), 4.45 (2H, m), 4.56 (2H, s), 7.14 (2H, d), 7.90 (1H, d), 8.05-8.19 (4H, m), 8.28 (1H, s), 8.76 (1H, br s), 8.79 (1H, s), 10.00 (1H, br s), 10.16 (1H, s). LCMS: Rt 1.98 min (99.1%), m/z (APCI) 472 (M+H)+.

Aufarbeitung

  1. customThis compound may be prepared
  2. customThe reaction mixture is purified by silica gel column chromatography
  3. washeluting with DCM

Quellen und Nachweise

ORD-Eintrag
ord-f37c66fbaf54414d942607fe743c0a3a
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07915256B2

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