Diisopropylethylamine → N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 77581

Reaktionsgleichung

Reaktionsgleichung von HRID 77581
[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]23[CH2:16][NH:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1.[F:26][C:27]1[CH:28]=[N:29][C:30](Cl)=[N:31][CH:32]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1.O>[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]23[CH2:16][N:15]([C:30]4[N:31]=[CH:32][C:27]([F:26])=[CH:28][N:29]=4)[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:25])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 5834662-Chloro-5-fluoropyrimidineHCID 86762765N-[(4aR,7aS)-7a-(3-Aminophenyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

Produkt 1

HCID 86762768N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamideAusbeute 79,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of N-[(4aR,7aS)-7a-(3-aminophenyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (2.49 g, 7.06 mmol), 5-fluoro-2-chloropyrimidine (3.74 g, 28.26 mmol), and diisopropylethylamine (6.16 mL, 35.32 mmol) in 1,4-dioxane (60 mL) is heated to reflux for 4 hours under nitrogen. The reaction is cooled, diluted with water and extracted with ethyl acetate (3×). The combined organic extracts are dried over sodium sulfate, filtered and the solvent is removed in vacuo to give the crude product. The crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient to give the title compound (2.51 g, 79%). ES/MS (m/e): 449 (M+H).

Aufarbeitung

  1. temperatureto reflux for 4 hours under nitrogen
  2. temperatureThe reaction is cooled
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organic extracts are dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent is removed in vacuo
  7. customto give the crude product
  8. customThe crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient

Quellen und Nachweise

ORD-Eintrag
ord-66ea0de20f9a4ae38c13d32f501816e4
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841293B1

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