Potassium Carbonate → (S)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 519140

Reaktionsgleichung

Reaktionsgleichung von HRID 519140
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2Br)[O:24][CH2:23][C:22]2[N:17]3[C@H:18]([CH3:30])[C:19](=[O:29])[NH:20][N:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:37]([O:39]/[CH:40]=[CH:41]/B1OC(C)(C)C(C)(C)O1)[CH3:38]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2/[CH:38]=[CH:37]/[O:39][CH2:40][CH3:41])[O:24][CH2:23][C:22]2[N:17]3[C@H:18]([CH3:30])[C:19](=[O:29])[NH:20][N:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 219739081-Ethoxyethene-2-boronic acid pinacol esterHCID 86727532(S)-3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 86727531(S)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 102,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a mixture of (S)-3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.6 g, 1.249 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.051 g, 0.060 mmol) and K2CO3 (0.259 g, 1.87 mmol) in dioxane (24 mL) and water (4 mL) was added (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.124 g, 0.62 mmol) and the reaction mixture was stirred at 100° C. for 3 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo to give the crude product, which was purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether) to give (S)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.3 g, 50%) as a light yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.16 (s, 1H), 6.73 (s, 1H), 6.61 (d, J=12.4 Hz, 1H), 6.07 (s, 1H), 5.56 (d, J=12.4 Hz, 1H), 5.23 (s, 1H), 4.65 (m, 1H), 4.37-4.52 (m, 2H), 3.77-3.96 (m, 3H), 3.64 (m, 1H), 3.35 (m, 2H), 3.08-3.31 (m, 1H), 2.06-2.22 (m, 1H), 1.82 (m, 1H), 1.42 (m, 12H), 1.28 (t, J=7.2 Hz, 3H). LC/MS (Table 1, Method 2) Rt=1.097 min.; MS m/z: 472 [M+H]+. SFC (Table 1, Method 37) Rt=1.919 min.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customto give the crude product, which
  4. customwas purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-8b29e45f1d06414a866233dcf153855b
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115151B2

Verknüpfte Notizen

Wird geladen…