5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one → 5-(8-(4-(4-Isopropylpiperazin-1-yl)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

HRID 605921

Reaktionsgleichung

Reaktionsgleichung von HRID 605921
[CH3:1][N:2]1CCN(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:44]=N[C:46]([N:49]3[CH2:54][CH2:53][N:52]([CH:55]([CH3:57])[CH3:56])[CH2:51][CH2:50]3)=[CH:47][CH:48]=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>[NH3:2].[CH:55]([N:52]1[CH2:51][CH2:50][N:49]([C:46]2[CH:1]=[CH:44][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:48][CH:47]=2)[CH2:54][CH2:53]1)([CH3:56])[CH3:57]

Komponenten

8

Edukt 3

HCID 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 57590080(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[6-(4-isopropylpiperazin-1-yl)pyridin-3-yl]amine

Produkt 2

HCID 222AmmoniaHCID 248891195-(8-(4-(4-Isopropylpiperazin-1-yl)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-oneAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 10340Sodium CarbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

This compound may be prepared using methods as described for Compound 6, step 4 using 5-bromo-N-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine (0.6 g, 1.44 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (0.56 g, 2.16 mmol) and Pd(PPh3)4 (0.416 g, 0.36 mmol) in 1.5M Na2CO3 (7.7 mL) and dioxane (23 mL). Purification by silica gel column chromatography eluting with DCM followed by 98:2 DCM:NH3 (7M in MeOH) affords the title compound (0.36 g, 53%) which is converted into the mesylate salt using 1M methanesulfonic acid in MeOH (0.77 mL). After trituration with diethyl ether and DCM the title compound is isolated as a solid (0.410 g). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 1.35 (6H, d), 2.35 (3H, s, MsOH), 3.04 (2H, t), 3.20-3.27 (2H, m), 3.56-3.63 (3H, m), 3.89 (2H, d), 4.52 (2H, s), 7.09 (2H, d), 7.85 (1H, d), 7.95-8.01 (3H, m), 8.10 (1H, d), 8.24 (1H, s), 8.72 (1H, s), 8.74 (1H, s), 9.27 (1H, br s), 10.07 (1H, s). LCMS: Rt 2.93 min (97.9%), m/z (ES+) 469 (M+H)+.

Aufarbeitung

  1. customThis compound may be prepared
  2. customPurification by silica gel column chromatography
  3. washeluting with DCM

Quellen und Nachweise

ORD-Eintrag
ord-364503f562f64d7b9f88b07568c02454
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07915256B2

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