5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one → 5-(8-(6-(4-Isopropylpiperazin-1-yl)pyridin-3-ylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

HRID 1783968

Reaktionsgleichung

Reaktionsgleichung von HRID 1783968
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:44]=[N:45][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>[CH:55]([N:52]1[CH2:53][CH2:54][N:49]([C:46]2[N:45]=[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)[CH2:50][CH2:51]1)([CH3:57])[CH3:56]

Komponenten

7

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 1

HCID 248906455-(8-(6-(4-Isopropylpiperazin-1-yl)pyridin-3-ylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

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 (50 mg, 0.12 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (56 mg, 0.216 mmol) and Pd(PPh3)4 (35 mg, 0.03 mmol) in 1.5M Na2CO3 (0.64 mL) and dioxane (2 mL). The crude product is purified by silica gel column chromatography eluting with 95:5 DCM:MeOH followed by 90:10 DCM:MeOH. The title compound is obtained after trituration with a 10:1 mixture n-hexane:DCM (19 mg, 34%). Conversion into the mesylate salt, using 0.1M methanesulfonic acid (0.35 mL), gives the title compound as a yellow solid (20 mg, 69%).

Aufarbeitung

  1. customThis compound may be prepared
  2. customThe crude product is purified by silica gel column chromatography
  3. washeluting with 95:5 DCM

Quellen und Nachweise

ORD-Eintrag
ord-bd472570412c4388a8695015086d4763
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07501411B2

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