Dichloromethane → tert-Butyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

HRID 1626672Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1626672
Cl[C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[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.[CH:24]1([NH:27][C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[C:33]([F:46])[CH:32]=2)=[O:29])[CH2:26][CH2:25]1.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].O.CCO.COCCOC>[CH:24]1([NH:27][C:28](=[O:29])[NH:30][C:31]2[CH:36]=[CH:35][C:34]([C:2]3[N:3]=[C:4]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[C:5]4[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][C:6]=4[N:7]=3)=[C:33]([F:46])[CH:32]=2)[CH2:25][CH2:26]1

Komponenten

9

Edukt 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666792291-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 71540665Tert-butyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-D]pyrimidine-6(7H)-carboxylate2×

Produkt 1

HCID 66687725tert-Butyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylateAusbeute 58 %

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 tert-butyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 2) (85 mg, 0.25 mmol), 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (100 mg, 0.31 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (10 mg, 0.012 mmol) and sodium carbonate (40 mg, 0.38 mmol) in 2 ml of a 7:3:2 mixture of DME:EtOH:H2O respectively was heated in the microwave at 130° C. for 30 minutes. The mixture was filtered through a celite 545 pre-packed cartridge (2.5 g), washed with MeOH and the solvent removed in vacuo. The residue was purified by prep. HPLC at low pH, yielding the title compound (72 mg, 0.14 mmol, 58%).

Aufarbeitung

  1. filtrationThe mixture was filtered through a celite 545 pre-packed cartridge (2.5 g)
  2. washwashed with MeOH
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by prep

Quellen und Nachweise

ORD-Eintrag
ord-13e0d4d201364287ac17c21b245e621a
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785457B2

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