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

HRID 1783928Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1783928
C[N:2]1CCN([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[C:16]4[N:17]([N:29]=[CH:30][N:31]=4)[C:18]([C:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=4)=[CH:19][N:20]=3)=[CH:10][CH:9]=2)CC1.BrC1N2N=CN=C2C(NC2C=CC([O:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=CC=2)=NC=1.CC1(C)C(C)(C)OB(C2C=C(C(N)=O)SC=2)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].[O:55]1[CH2:56][CH2:57][N:52]([CH2:51][CH2:50][O:49][C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[C:16]4[N:17]([N:29]=[CH:30][N:31]=4)[C:18]([C:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=4)=[CH:19][N:20]=3)=[CH:10][CH:9]=2)[CH2:53][CH2:54]1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 575900074-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxamideHCID 57590052(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine

Produkt 2

HCID 222AmmoniaHCID 248894674-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)thiophene-2-carboxamideAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

This compound may be prepared using 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 (113 mg, 0.27 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxamide (136 mg, 0.537 mmol), and Pd(PPh3)4 (78 mg, 0.067 mmol) in 1.5M Na2CO3 (1.44 mL, 2.16 mmol) and dioxane (4.3 mL). The reaction mixture is purified by silica gel column chromatography eluting with 97:3 DCM:NH3 (7M in MeOH) to yield the title compound (65 mg, 52%). LCMS: Rt 1.98 min (98.9%). Conversion into the mesylate salt using 0.1M methanesulfonic acid in MeOH (1.1385 mL) affords the title compound (50 mg, 95%). 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 2.37 (3H, s, MsOH), 3.21-3.64 (6H, m), 3.76 (2H, t), 4.05 (2H, d), 4.40 (2H, m), 7.09 (2H, d), 7.61 (1H, br s), 8.02 (2H, d), 8.11 (2H, s), 8.48 (1H, s), 8.67 (1H, s), 8.82 (1H, s), 9.91 (1H, br s), 10.09 (1H, s). LCMS: Rt 1.98 min (97.7%), m/z (APCI) 466 (M+H)+.

Aufarbeitung

  1. customThis compound may be prepared
  2. customThe reaction mixture is purified by silica gel column chromatography
  3. washeluting with 97:3 DCM

Quellen und Nachweise

ORD-Eintrag
ord-573e8af24c15454793a5a9bb824c9cdf
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07501411B2

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