Potassium Carbonate → (S)-3-[(S)-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-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 519156

Reaktionsgleichung

Reaktionsgleichung von HRID 519156
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@:10]([NH:14][C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2Br)[O:25][CH2:24][C:23]2[N:18]3[C@@H:19]([CH3:31])[C:20](=[O:30])[NH:21][N:22]=2)([CH3:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:38]([O:40]/[CH:41]=[CH:42]/B1OC(C)(C)C(C)(C)O1)[CH3:39]>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@@:10]([NH:14][C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2/[CH:39]=[CH:38]/[O:40][CH2:41][CH3:42])[O:25][CH2:24][C:23]2[N:18]3[C@@H:19]([CH3:31])[C:20](=[O:30])[NH:21][N:22]=2)([CH3:13])[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 86727550(S)-3-((S)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 86727549(S)-3-[(S)-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-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of (S)-3-((S)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (isomer A, SFC (Table 1, Method 52) Rt=2.880 min, 0.030 g, 0.061 mmol), K2CO3 (0.017 g, 0.121 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.018 g, 0.091 mmol) and PdCl2(dppf)-CH2Cl2 adduct (4.96 mg, 6.07 μmol) in dioxane (2 mL) and water (0.3 mL) was stirred at 90° C. for 14 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 3%˜20% EtOAc in petroleum ether) to give (S)-3-[(S)-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-pyrrolidine-1-carboxylic acid tert-butyl ester (10 mg, 34%) as a pale solid. LC/MS (Table 1, Method 25) Rt=0.826 min; MS m/z: 508 [M+Na]+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (eluting with 3%˜20% EtOAc in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-096b5ee617fc4f2cb2298c540de7c6c7
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115151B2

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