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Dichloromethane → (S)-tert-butyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6-(7H)-carboxylate

HRID 1626681
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1626681
Cl[C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@@H:19]2[CH3:24])[C:5]2[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH2:25]([NH:27][C:28]([NH:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[C:33]([F:46])[CH:32]=1)=[O:29])[CH3:26].ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>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].CCO.O.COCCOC>[CH2:25]([NH:27][C:28](=[O:29])[NH:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[N:3]=[C:4]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][C@@H:19]3[CH3:24])[C:5]3[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][C:6]=3[N:7]=2)=[C:33]([F:46])[CH:32]=1)[CH3:26]
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Komponenten

9

Edukt 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666787871-Ethyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 86663148(S)-tert-butyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate2×

Produkt 1

HCID 66678969
(S)-tert-butyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6-(7H)-carboxylate
Ausbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A solution of (S)-tert-butyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 1) (214 mg, 0.603 mmol), 1-ethyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 28) (211 mg, 0.685 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (25 mg, 0.0306 mmol) and sodium carbonate (179 mg, 1.69 mmol) in 2 ml of a 7:3:1 mixture of DME:H2O:EtOH respectively was heated in the microwave at 115° C. for 45 minutes then at 130° C. for 15 minutes. The reaction mixture was concentrated in vacuo and the residue was re-dissolved in a mix of H2O and EtOAc. The aqueous phase was basified by the addition of aqueous NaOH and extracted into EtOAc. The organic extracts were combined, dried over magnesium sulphate and concentrated in vacuo. The sample was purified via preparative HPLC at low pH to yield the title compound (36 mg, 13%).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was re-dissolved in
  3. additiona mix of H2O and EtOAc
  4. additionThe aqueous phase was basified by the addition of aqueous NaOH
  5. extractionextracted into EtOAc
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe sample was purified via preparative HPLC at low pH

Quellen und Nachweise

ORD-Eintrag
ord-7bcfc773b7904f219d53ca0d282bed26
Quelldatensatz
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08785457B2

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