Diisopropylethylamine → N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-2-methoxy-N'-methyl-N'-(2-(4-methylpiperazin-1-yl)ethyl]-5-nitrobenzene-1,4-diamine

HRID 1842762

Reaktionsgleichung

Reaktionsgleichung von HRID 1842762
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21](F)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1.[CH3:39][NH:40][CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]1>CC(N(C)C)=O>[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21]([N:40]([CH3:39])[CH2:41][CH2:42][N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 14979290N-Methyl-2-(4-methylpiperazin-1-yl)ethan-1-amine3×HCID 712393485-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Produkt 1

HCID 71240746N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-2-methoxy-N'-methyl-N'-(2-(4-methylpiperazin-1-yl)ethyl]-5-nitrobenzene-1,4-diamineAusbeute 67,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

DIPEA (0.105 mL, 0.60 mmol) was added to a mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 20, 0.207 g, 0.5 mmol) and N-methyl-2-(4-methylpiperazin-1-yl)ethanamine (Intermediate 109, 0.079 g, 0.50 mmol) in DMA (5 mL). The mixture was heated in a microwave at 140° C. for 3 h. An additional portion of N-methyl-2-(4-methylpiperazin-1-yl)ethanamine (8 mg, 0.05 mmol) was added and the mixture was heated in a microwave at 140° C. for a further 1 h before being cooled to r.t. The mixture was then concentrated in vacuo and the residue was dissolved in CH3OH. Purification by ion exchange chromatography, using an SCX column and eluting with 1M methanolic ammonia provided crude material after concentration of appropriate fractions in vacuo. Further purification by FCC, eluting with 2-8% CH3OH in CH2Cl2 gave the title compound (0.186 g, 67%) as an orange foam; 1H NMR: (CDCl3) 2.26 (3H, s), 2.32-2.45 (4H, m), 2.45-2.57 (4H, m), 2.61 (2H, t), 2.89 (3H, s), 3.29 (2H, t), 3.98 (3H, s), 6.65 (1H, s), 6.93-7.00 (1H, m), 7.38 (1H, ddd), 7.44 (1H, s), 8.40 (1H, s), 8.49 (1H, d), 8.55 (1H, d), 8.91 (2H, d); m/z: ES+ MH+ 552.59.

Aufarbeitung

  1. temperaturethe mixture was heated in a microwave at 140° C. for a further 1 h
  2. temperaturebefore being cooled to r.t
  3. concentrationThe mixture was then concentrated in vacuo
  4. dissolutionthe residue was dissolved in CH3OH
  5. customPurification by ion exchange chromatography
  6. washeluting with 1M methanolic ammonia
  7. customprovided crude material after concentration of appropriate fractions in vacuo
  8. customFurther purification by FCC
  9. washeluting with 2-8% CH3OH in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-61da6146b3b643aabc39ee47552bc3bb
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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