Sodium Carbonate → 4-(8-(4-Morpholinophenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)furan-2-carboxamide

HRID 1783936

Reaktionsgleichung

Reaktionsgleichung von HRID 1783936
C[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:48]=[CH:47][C:46]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[CH:45][CH:44]=2)=[N:35][CH:34]=1.CC1(C)C(C)(C)OB([C:63]2[CH:64]=[C:65]([C:68]([NH2:70])=[O:69])[O:66][CH:67]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>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.O1CCOCC1>[NH3:2].[O:52]1[CH2:53][CH2:54][N: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:63]4[CH:64]=[C:65]([C:68]([NH2:70])=[O:69])[O:66][CH:67]=4)=[CH:34][N:35]=3)=[CH:44][CH:45]=2)[CH2:50][CH2:51]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 57589931(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-ylphenyl)amineHCID 575899904-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)furan-2-carboxamide

Produkt 2

HCID 222AmmoniaHCID 575899894-(8-(4-Morpholinophenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)furan-2-carboxamideAusbeute 65 %

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-morpholin-4-yl-phenyl)-amine (78 mg, 0.16 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-furan-2-carboxylic acid amide (100 mg, 0.34 mmol), and Pd(PPh3)4 (60 mg, 0.052 mmol) in 1.5M Na2CO3 (aq) (1.1 mL, 1.68 mmol), and dioxane (3 mL). The reaction mixture is partitioned between water and ethyl acetate, the title compound precipitates and is collected by filtration. Purification of the solid by silica gel column chromatography, eluting with DCM and 95:5 DCM:NH3 (7M in MeOH), affords the title compound (42 mg, 65%). Conversion into the mesylate salt using 0.1M methanesulfonic acid (0.82 mL) gives a solid which is triturated with diethyl ether to afford the title compound (30.5 mg). 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 2.19 (3H, s, MsOH), 3.03-3.07 (4H, m), 3.67 (4H, m), 6.99 (2H, br s), 7.43 (1H, d), 7.74-7.82 (4H, m), 8.06 (1H, br s), 8.59 (1H, br s), 8.64 (1H, s), 9.91 (1H, br s). LCMS: Rt 2.64 min (98.1%), m/z (APCI) 406 (M+H)+.

Aufarbeitung

  1. customThis compound may be prepared
  2. customThe reaction mixture is partitioned between water and ethyl acetate
  3. customthe title compound precipitates
  4. filtrationis collected by filtration
  5. customPurification of the solid by silica gel column chromatography
  6. washeluting with DCM and 95:5 DCM

Quellen und Nachweise

ORD-Eintrag
ord-2462972170de4c979b2ad2ad40df4acf
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07501411B2

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