1,3-Dioxolane-4-methanol → 3-Amino-5-chloro-6-([1,3]dioxolan-4-ylmethoxy)-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

HRID 656660

Reaktionsgleichung

Reaktionsgleichung von HRID 656660
[CH2:1]1[O:5][CH2:4][O:3][CH:2]1[CH2:6][OH:7].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:18]1([NH:21][C:22]([C:24]2[S:37][C:27]3=[N:28][C:29](S(C)=O)=[C:30]([Cl:33])[C:31]([CH3:32])=[C:26]3[C:25]=2[NH2:38])=[O:23])[CH2:20][CH2:19]1>C1COCC1>[CH:18]1([NH:21][C:22]([C:24]2[S:37][C:27]3=[N:28][C:29]([O:7][CH2:6][CH:2]4[CH2:1][O:5][CH2:4][O:3]4)=[C:30]([Cl:33])[C:31]([CH3:32])=[C:26]3[C:25]=2[NH2:38])=[O:23])[CH2:20][CH2:19]1

Komponenten

5

Edukt 3

HCID 216181,3-Dioxolane-4-methanolHCID 2733832Lithium HexamethyldisilazideHCID 576644203-Amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

Produkt 1

HCID 576644213-Amino-5-chloro-6-([1,3]dioxolan-4-ylmethoxy)-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamideAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of glycerol formal (0.729 g, 7.0 mmol) in THF (3 ml) at room temperature is added dropwise a solution of lithium bis(trimethylsilyl)amide (1.0 M in hexanes)(3.50 ml, 3.50 mmol). The reaction mixture is stirred for 15 minutes and then is treated with 3-amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide (0.345 g, 1.00 mmol). The reaction mixture is heated at 75° C. in a sealed tube for 1.5 hours, cooled to room temperature, and then quenched by the addition of water (10 ml). The reaction mixture is transferred to an erlenmeyer flask and diluted to 75 ml with water. The mixture is cooled to 0° C. and stirred. During this time, a white precipitate is formed. This solid is collected by filtration and slurried in a 2:1 EtOAc:hexane mixture. This slurry is stirred for 10 minutes, filtered, and the collected solid is placed in the vacuum oven to dry (60° C. for 16 hours). This affords the title compound as a white solid (0.195 g, 51%). Mass (m/z): 384.1 (M++1), 382.1 (M+−1).

Aufarbeitung

  1. temperaturecooled to room temperature
  2. customquenched by the addition of water (10 ml)
  3. customThe reaction mixture is transferred to an erlenmeyer flask
  4. additiondiluted to 75 ml with water
  5. temperatureThe mixture is cooled to 0° C.
  6. stirringstirred
  7. customDuring this time, a white precipitate is formed
  8. filtrationThis solid is collected by filtration
  9. stirringThis slurry is stirred for 10 minutes
  10. filtrationfiltered
  11. customto dry (60° C. for 16 hours)

Quellen und Nachweise

ORD-Eintrag
ord-1e68c9412ca04864b8f2ee997b02c5aa
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071776B2

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