Dichloromethane → 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]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

HRID 519135

Reaktionsgleichung

Reaktionsgleichung von HRID 519135
[C:1]([O:5][C:6]([N:8]1[CH2:11][C: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)([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:31]([O:33]/[CH:34]=[CH:35]/B1OC(C)(C)C(C)(C)O1)[CH3:32].C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>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:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([NH:13][C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2/[CH:32]=[CH:31]/[O:33][CH2:34][CH3:35])[O:24][CH2:23][C:22]2[N:17]3[C@H:18]([CH3:30])[C:19](=[O:29])[NH:20][N:21]=2)([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 219739081-Ethoxyethene-2-boronic acid pinacol esterHCID 867275233-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 867275243-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-3-methyl-azetidine-1-carboxylic acid tert-butyl esterAusbeute 72,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of 3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (12.7 g, 26.4 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.85 g, 39.7 mmol), Pd(dppf)Cl2.CH2Cl2 adduct (4.32 g, 5.29 mmol) and K2CO3 (7.31 g, 52.9 mmol) in dioxane (210 mL) and water (35 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether) to give 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]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (9 g, 72%). 1H NMR (CD3OD, 400 MHz): δ 6.88 (s, 1H), 6.81 (d, J=12.5 Hz, 1H), 5.99 (brs, 1H), 5.85 (d, J=12.5 Hz, 1H), 4.97-4.93 (m, 1H), 4.70 (m, 2H), 4.06 (m, 2H), 3.93 (m, 4H), 1.61 (s, 3H), 1.48-1.44 (m, 12H), 1.33 (s, 3H).

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-213a1511e1fb443e88fa6c4a1d09711f
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115151B2

Verknüpfte Notizen

Wird geladen…