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

HRID 1626680
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1626680
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]2[CH3:21])[C:5]2[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH2:22]([NH:24][C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[C:30]([F:43])[CH:29]=1)=[O:26])[CH3:23].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>[CH2:22]([NH:24][C:25](=[O:26])[NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[N:3]=[C:4]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]3[CH3:21])[C:5]3[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=3[N:7]=2)=[C:30]([F:43])[CH:29]=1)[CH3:23]
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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 86663170(S)-methyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate2×

Produkt 1

HCID 66678967
(S)-methyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6-(7H)-carboxylate
Ausbeute 4,2 %

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)-methyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 26) (98 mg, 0.313 mmol), 1-ethyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 28) (110 mg, 0.357 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (13 mg, 0.0157 mmol) and sodium carbonate (93 mg, 0.876 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. The reaction was concentrated in vacuo and the residue was re-dissolved in a mix of H2O and EtOAc. The aqueous phase was extracted into EtOAc and the organic extracts were combined and concentrated in vacuo. The sample was then purified via preparative HPLC at low pH and then triturated in MeOH and filtered to yield the title compound (6 mg, 4%).

Aufarbeitung

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue was re-dissolved in
  3. additiona mix of H2O and EtOAc
  4. extractionThe aqueous phase was extracted into EtOAc
  5. concentrationconcentrated in vacuo
  6. customThe sample was then purified via preparative HPLC at low pH
  7. customtriturated in MeOH
  8. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-2acafa66c7984fbba5a19901a92565d8
Quelldatensatz
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08785457B2

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