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

HRID 605910Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 605910
C[N:2]1CCN(C2C=CC(NC3C4N(N=CN=4)C([C:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=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(C2SC(C(N)=O)=CC=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: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:25]4[S:24][C:23]([C:26]([NH2:28])=[O:27])=[CH:22][CH:21]=4)=[CH:34][N:35]=3)=[CH:44][CH:45]=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 575899405-(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 248894665-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)thiophene-2-carboxamideAusbeute 25 %

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 (118 mg, 0.28 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxamide (142 mg, 0.56 mmol), and Pd(PPh3)4 (81 mg, 0.07 mmol) in 1.5M Na2CO3 (1.5 mL, 2.24 mmol) and dioxane (4.5 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 (33 mg, 25%). LCMS: Rt 2.66 min (99%). Conversion into the mesylate salt using 0.1M methanesulfonic acid in MeOH (0.569 mL) affords the title compound (24 mg, 86%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.37 (3H, s, MsOH), 3.25 (2H, m), 3.50-3.64 (4H, m), 3.76 (2H, t), 4.05 (2H, d), 4.40 (2H, m), 7.09 (2H, d), 7.51 (1H, br s), 7.87 (1H, d), 7.99-8.05 (3H, m), 8.11 (1H, br s), 8.37 (1H, s), 8.84 (1H, s), 9.92 (1H, br s), 10.21 (1H, s). LCMS: Rt 1.95 min (98.8%), 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-82c3aa70ad73448794aba2b3dfec8923
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07915256B2

Notizen zur Reaktion

Wird geladen…