3-Butyn-1-OL → 2-(but-3-yn-1-yloxy)-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone

HRID 870563

Reaktionsgleichung

Reaktionsgleichung von HRID 870563
[H-].[Na+].[CH2:3]([OH:7])[CH2:4][C:5]#[CH:6].Cl[CH2:9][C:10]([N:12]1[CH2:31][CH2:30][C:15]2[N:16]=[C:17]([NH:20][CH:21]3[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH2:22]3)[N:18]=[CH:19][C:14]=2[CH2:13]1)=[O:11].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:3]([O:7][CH2:9][C:10]([N:12]1[CH2:31][CH2:30][C:15]2[N:16]=[C:17]([NH:20][CH:21]3[CH2:22][C:23]4[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:29]3)[N:18]=[CH:19][C:14]=2[CH2:13]1)=[O:11])[CH2:4][C:5]#[CH:6]

Komponenten

6

Edukt 4

HCID 135663-Butyn-1-OLHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 867265282-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone

Produkt 1

HCID 867265292-(but-3-yn-1-yloxy)-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanoneAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

To sodium hydride (60 wt % in mineral oil, 1.58 g, 39.6 mmol) in tetrahydrofuran (50 mL) at 23° C., add 3-butyn-1-ol (7.93 g, 8.59 mL, 113.2 mmol) dropwise, then stir at 23° C. for 20 minutes. Add this solution to 2-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone (9.70 g, 28.3 mmol) in tetrahydrofuran (150 mL) at 23° C. and stir for one hour. Pour the reaction mixture into 50% saturated aqueous sodium bicarbonate solution. Separate the organic layer and further extract the aqueous layer with ethyl ether (×2) and ethyl acetate (×2). Combine the organic extracts and wash with brine, then dry over anhydrous sodium sulfate, filter, and concentrate. Purify the resulting crude product by silica gel column chromatography (gradient elution: 20% ethyl acetate in hexanes to 100% ethyl acetate) to give the title compound (8.16 g, 77%). MS (m/z): 377 (M+1).

Aufarbeitung

  1. stirringstir for one hour
  2. customSeparate the organic layer
  3. extractionfurther extract the aqueous layer with ethyl ether (×2) and ethyl acetate (×2)
  4. washCombine the organic extracts and wash with brine
  5. dry with materialdry over anhydrous sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify the resulting crude product
  9. washby silica gel column chromatography (gradient elution: 20% ethyl acetate in hexanes to 100% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-ecdc455bcbe84507bc1a5ece1f0be124
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969555B2

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