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Diisopropylethylamine → 4-{5-[(6,7-Dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorophenyl}-1-methyl-3,5-dioxopiperazin-1-ium trifluoroacetate

HRID 1172803
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1172803
[CH3:1][N:2]1[CH2:7][C:6](=[O:8])O[C:4](=[O:9])[CH2:3]1.[F:10][C:11]([F:16])([F:15])[C:12]([O-:14])=[O:13].[Cl:17][C:18]1[N:22]2[C:23]([CH2:28][C:29]3[CH:30]=[CH:31][C:32]([F:36])=[C:33]([NH3+:35])[CH:34]=3)=[CH:24][NH:25][C:26](=[O:27])[C:21]2=[CH:20][C:19]=1[Cl:37].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.O.CC#N>[F:10][C:11]([F:16])([F:15])[C:12]([O-:14])=[O:13].[Cl:17][C:18]1[N:22]2[C:23]([CH2:28][C:29]3[CH:30]=[CH:31][C:32]([F:36])=[C:33]([N:35]4[C:4](=[O:9])[CH2:3][NH+:2]([CH3:1])[CH2:7][C:6]4=[O:8])[CH:34]=3)=[CH:24][NH:25][C:26](=[O:27])[C:21]2=[CH:20][C:19]=1[Cl:37]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 143203244-Methylmorpholine-2,6-dioneHCID 866334295-[(6,7-Dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorobenzenaminium trifluoroacetate

Produkt 1

HCID 86633434
4-{5-[(6,7-Dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorophenyl}-1-methyl-3,5-dioxopiperazin-1-ium trifluoroacetate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of 4-methylmorpholine-2,6-dione (1 eq) (see for Ref. WO 03/093261) in toluene (0.06 M) was added N2 (Example 14, step 2). The reaction mixture was refluxed for 2 h and then allowed to stand at RT overnight. The solvent was removed under reduced pressure. The resulting crude was dissolved in DMF (0.2 M) and to the resulting solution were added sequentially TBTU (1.3 eq), DIPEA (2.2 eq) and DMAP (0.3 eq). The mixture was stirred at RT for 2 h and then the product was isolated by purification at prep RP-HPLC using H2O (+0.1% TFA) and MeCN (+0.1% TFA) as eluents (C18 column). The desired fractions were lyophilized to afford the desired compound as a white powder. 1H NMR (400 MHz, DMSO-d6+TFA) δ: 7.41-7.27 (2H, m), 7.14 (1H, s), 7.08 (1H, d, J=6.8 Hz), 6.59 (1H, br. s), 4.38 (2H, s), 4.25 (4H, m), 2.85 (3H, s). MS (ES) C19H15Cl2FN4O3 requires: 436/438, found: 437/439 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was refluxed for 2 h
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThe resulting crude was dissolved in DMF (0.2 M) and to the resulting solution
  4. customthe product was isolated by purification at prep RP-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-c1f1a265a458444ba2cfc89ec791758f
Quelldatensatz
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07834015B2

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