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1-Methylpiperazine → 2-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-{6-[6-(methyloxy)-5-({[2-(4-methyl-1-piperazinyl)ethyl]sulfonyl}amino)-3-pyridinyl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide

HRID 1695791
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1695791
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([CH2:9][C:10]2[S:11][CH:12]=[C:13]([C:15]([NH:17][C:18]3[C:19]4[C:23]([CH:24]=[C:25]([C:27]5[CH:28]=[N:29][C:30]([O:39][CH3:40])=[C:31]([NH:33][S:34]([CH:37]=[CH2:38])(=[O:36])=[O:35])[CH:32]=5)[CH:26]=3)=[N:22][N:21](C3CCCCO3)[CH:20]=4)=[O:16])[N:14]=2)[CH2:3]1.[CH3:47][N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1>C(#N)C>[CH3:8][C@H:6]1[O:7][C@@H:2]([CH3:1])[CH2:3][N:4]([CH2:9][C:10]2[S:11][CH:12]=[C:13]([C:15]([NH:17][C:18]3[CH:26]=[C:25]([C:27]4[CH:28]=[N:29][C:30]([O:39][CH3:40])=[C:31]([NH:33][S:34]([CH2:37][CH2:38][N:51]5[CH2:52][CH2:53][N:48]([CH3:47])[CH2:49][CH2:50]5)(=[O:35])=[O:36])[CH:32]=4)[CH:24]=[C:23]4[C:19]=3[CH:20]=[N:21][NH:22]4)=[O:16])[N:14]=2)[CH2:5]1
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Komponenten

4

Edukt 2

HCID 531671-MethylpiperazineHCID 669112332-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-[6-[5-[(ethenylsulfonyl)amino]-6-(methyloxy)-3-pyridinyl]-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Produkt 1

HCID 445400352-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-{6-[6-(methyloxy)-5-({[2-(4-methyl-1-piperazinyl)ethyl]sulfonyl}amino)-3-pyridinyl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342
Acetonitrile
Lösungsmittel

Versuchsvorschrift

Acetonitrile (10 ml) was added to 2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-N-[6-[5-[(ethenylsulfonyl)amino]-6-(methyloxy)-3-pyridinyl]-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (250 mg) followed by 1-methylpiperazine (0.33 ml). The reaction was stirred at RT for 3 hours. The reaction was evaporated to dryness and the residue was separated between DCM and water. The DCM was passed through a hydrophobic frit then evaporated to dryness. The residue was dissolved in DMSO:methanol (1:1, v/v, 2 ml) and purified by MDAP (method E). Pure fractions were combined and evaporated to dryness. Analysis showed complete deprotection on dry-down to give title compound (116 mg).

Aufarbeitung

  1. customThe reaction was evaporated to dryness
  2. customthe residue was separated between DCM and water
  3. customthen evaporated to dryness
  4. dissolutionThe residue was dissolved in DMSO:methanol (1:1, v/v, 2 ml)
  5. custompurified by MDAP (method E)
  6. customevaporated to dryness
  7. customon dry-down

Quellen und Nachweise

ORD-Eintrag
ord-7f8d81f67b8744c6a647ce9627fba134
Quelldatensatz
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08163743B2

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