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Cesium carbonate → 3-Methoxy-N-methyl-4-((5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide

HRID 529662
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 529662
Cl[C:2]1[N:3]=[C:4]([O:25][CH:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:5]2[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=2[N:7]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[NH2:74][C:75]1[CH:84]=[CH:83][C:78]([C:79]([NH:81][CH3:82])=[O:80])=[CH:77][C:76]=1[O:85][CH3:86].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:86][O:85][C:76]1[CH:77]=[C:78]([CH:83]=[CH:84][C:75]=1[NH:74][C:2]1[N:3]=[C:4]([O:25][CH:26]2[CH2:27][CH2:28][O:29][CH2:30][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:12]=[CH:13][N:14]=[CH:15][CH:16]=3)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:22])[CH3:24])[C:6]=2[N:7]=1)[C:79]([NH:81][CH3:82])=[O:80]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 204444344-Amino-3-methoxy-N-methylbenzamideHCID 867264362-Chloro-5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Produkt 1

HCID 86726437
3-Methoxy-N-methyl-4-((5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide
Ausbeute 49,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a solution of 2-chloro-5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.2 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv), 4-amino-3-methoxy-N-methylbenzamide (1.1 equiv) in 1,4-dioxane (0.1 M) was added cesium carbonate (3 equiv). The reaction mixtures were heated, with microwave irradiation, in a microwave reactor at 150° C. for 2 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then washed with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (magnesium sulfate), filtered, and concentrated. The crude was purified by silica gel column chromatography (0-90%) ethyl acetate (with 10% 1N ammonia in methanol) in hexane) to give the title compound (49.1% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.11 (s, 9 H) 0.85-0.93 (m, 2 H) 1.68-1.82 (m, 2 H) 2.06-2.18 (m, 2 H) 2.79 (d, J=4.30 Hz, 3 H) 3.51-3.66 (m, 4 H) 3.77-3.86 (m, 2 H) 3.96 (s, 3 H) 5.47-5.55 (m, 1 H) 5.56 (s, 2 H) 7.50-7.57 (m, 2 H) 7.71-7.76 (m, 2 H) 7.83 (s, 1 H) 7.92 (s, 1 H) 8.34 (q, J=4.43 Hz, 1 H) 8.52-8.60 (m, 3 H); MS (ESI) m/z 605.6 [M+1]+.

Aufarbeitung

  1. customThe reaction mixtures
  2. customThe reaction mixture was quenched with saturated aqueous sodium chloride
  3. washwashed with ethyl acetate
  4. washwashed with saturated aqueous sodium chloride
  5. dry with materialThe organic layer was dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by silica gel column chromatography (0-90%) ethyl acetate (with 10% 1N ammonia in methanol) in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-a2c525cd28af44a1ac3316f94b8f1daa
Quelldatensatz
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09346812B2

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