1-Butanol → 2-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)phenoxy)ethanol

HRID 558153Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 558153
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]3[C:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH2:24][CH2:25][O:26]C4CCCCO4)=[CH:14][CH:15]=[CH:16][C:10]=3[CH:9]=2)[C:5]([F:33])=[CH:4][N:3]=1.[N:34]1([CH2:39][CH2:40][NH2:41])[CH:38]=[CH:37][N:36]=[N:35]1.O1CCOCC1.C(O)CCC>C(O)(C)(C)C.C(Cl)(Cl)Cl.C(O)(C)C.CN1C(=O)CCC1.O1CCOCC1.CN1C(=O)CCC1>[N:34]1([CH2:39][CH2:40][NH:41][C:2]2[N:7]=[C:6]([C:8]3[S:12][C:11]4[C:13]([C:17]5[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=5[O:23][CH2:24][CH2:25][OH:26])=[CH:14][CH:15]=[CH:16][C:10]=4[CH:9]=3)[C:5]([F:33])=[CH:4][N:3]=2)[CH:38]=[CH:37][N:36]=[N:35]1

Komponenten

9

Edukt 4

HCID 2631-ButanolHCID 312751,4-DioxaneHCID 225619722-(1H-1,2,3-Triazol-1-yl)ethanamineHCID 866406622-Chloro-5-fluoro-4-(7-{2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-benzo[b]thiophen-2-yl)-pyrimidine

Produkt 1

HCID 592724752-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)phenoxy)ethanolAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6386tert-ButanolLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel2×HCID 17800835dioxane NMPLösungsmittelHCID 21906603Chloroform isopropyl alcoholLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

Combine 2-chloro-5-fluoro-4-(7-{2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-benzo[b]thiophen-2-yl)-pyrimidine (250 mg, 0.52 mmol) and 2-[1,2,3]triazol-1-yl-ethylamine (140 mg, 1.29 mmol) in tert-butanol (2.6 mL, alternative dioxane, n-butanol, dioxane-NMP, NMP alone as solvent) and NMP (1.3 mL) in a pressure vessel. Heat the mixture in an oil bath at 120-150° C. overnight (or in microwave reactor for a certain period of time). Dilute the mixture with chloroform/IPA (3/1). Wash the solution with aqueous saturated sodium chloride. Dry over sodium sulfate. Concentrate the solution in vacuo. Purify by column chromatography (DCM to 10% methanol in DCM) to give the title compound as a yellow solid (160 mg, 65%). MS (ES) m/z 477 [M+1]+.

Aufarbeitung

  1. washWash the solution with aqueous saturated sodium chloride
  2. dry with materialDry over sodium sulfate
  3. concentrationConcentrate the solution in vacuo
  4. customPurify by column chromatography (DCM to 10% methanol in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-7d6063710fb94076bf585c289e1ea82d
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063035B2

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