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Sodium Carbonate → (S)-2-(3-aminophenyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-methoxyphenyl)-5,11-dioxo-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yloxy)propyloxy)-10((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

HRID 594182
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 594182
[NH2:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH2:20][C@@H:21]3[N:27]([CH:28]=2)[C:26](=[O:29])[C:25]2[CH:30]=[C:31]([O:72][CH3:73])[C:32]([O:34][CH2:35][CH2:36][CH2:37][O:38][C:39]4[C:69]([O:70][CH3:71])=[CH:68][C:42]5[C:43](=[O:67])[N:44]6[CH:59]=[C:58](S(C(F)(F)F)(=O)=O)[CH2:57][C@H:45]6[C:46](=[O:56])[N:47]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[C:41]=5[CH:40]=4)=[CH:33][C:24]=2[N:23]([CH2:74][O:75][CH2:76][CH2:77][Si:78]([CH3:81])([CH3:80])[CH3:79])[C:22]3=[O:82])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O>[NH2:1][C:2]1[CH:3]=[C:4]([C:58]2[CH2:57][C@@H:45]3[N:44]([CH:59]=2)[C:43](=[O:67])[C:42]2[CH:68]=[C:69]([O:70][CH3:71])[C:39]([O:38][CH2:37][CH2:36][CH2:35][O:34][C:32]4[C:31]([O:72][CH3:73])=[CH:30][C:25]5[C:26](=[O:29])[N:27]6[CH:28]=[C:19]([C:16]7[CH:15]=[CH:14][C:13]([O:12][CH3:11])=[CH:18][CH:17]=7)[CH2:20][C@H:21]6[C:22](=[O:82])[N:23]([CH2:74][O:75][CH2:76][CH2:77][Si:78]([CH3:79])([CH3:81])[CH3:80])[C:24]=5[CH:33]=4)=[CH:40][C:41]=2[N:47]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:53])([CH3:54])[CH3:55])[C:46]3=[O:56])[CH:5]=[CH:6][CH:7]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 922693-Aminophenylboronic acidHCID 86676188HCID 86676188, Verbindung

Produkt 1

HCID 86676187(S)-2-(3-aminophenyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-methoxyphenyl)-5,11-dioxo-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yloxy)propyloxy)-10((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione
Ausbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

Solid 3-aminobenzeneboronic acid (0.143 g, 0.92 mmol) was added to a solution of the mono triflate (17) (0.619 g, 0.58 mmol), sodium carbonate (195 mg, 1.84 mmol) and palladium tetrakis triphenylphosphine (26.6 mg, 0.023 mmol) in toluene (10 mL), ethanol (5 mL) and water (5 mL). The reaction mixture was allowed to stir at room temperature for overnight at 30° C. The reaction mixture was then partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulphate. Excess solvent was removed by rotary evaporation under reduced pressure and the resulting residue was subjected to flash column chromatography (silica gel; gradient elution EtOAc/hexane 70/30→85/15). Removal of excess eluent from selected fractions afforded the desired product (0.502 g, 0.49 mmol, 85%).

Aufarbeitung

  1. customThe reaction mixture was then partitioned between ethyl acetate and water
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over magnesium sulphate
  4. customExcess solvent was removed by rotary evaporation under reduced pressure
  5. washthe resulting residue was subjected to flash column chromatography (silica gel; gradient elution EtOAc/hexane 70/30→85/15)
  6. customRemoval of excess eluent

Quellen und Nachweise

ORD-Eintrag
ord-909657ef5c084678b72a62e0ca184614
Quelldatensatz
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09242013B2

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