Isopropyl Acetate → HCID 59451925, Verbindung

HRID 1971257

Reaktionsgleichung

Reaktionsgleichung von HRID 1971257
Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[N:5]=[CH:4][CH:3]=1.Cl.[C:12]12(NC)[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][CH:14]([CH2:15]3)[CH2:13]1)[CH2:19]2.[Cl-].Cl[C:26]1N(C)CC[N+:27]=1[CH3:32].[OH-].[Na+].C([O:38]C(C)=O)(C)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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.[Fe+2].C(#N)C.O.CN(C=O)C>[C:12]12([CH2:32][NH:27][C:26]([C:2]3[N:7]4[CH:8]=[CH:9][N:10]=[C:6]4[N:5]=[CH:4][CH:3]=3)=[O:38])[CH2:13][CH:14]3[CH2:15][CH:16]([CH2:17][CH:18]([CH2:20]3)[CH2:19]1)[CH2:21]2

Komponenten

12

Edukt 5

HCID 7915Isopropyl AcetateHCID 14798Sodium HydroxideHCID 19477N-methyladamantan-1-amine hydrochlorideHCID 101763062-Chloro-1,3-dimethylimidazolinium chlorideHCID 469120805-Chloroimidazo[1,2-a]pyrimidine

Produkt 1

HCID 59451925HCID 59451925, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

In a ½ dram vial, 5-chloro-imidazo[1,2-a]pyrimidine (20.2 mg, 0.13 mmol), Zn(CN)2 (9.3 mg, 0.079 mmol), Pd2(dba)3 (3.0 mg, 0.003 mmol) and DPPF (3.6 mg, 0.006 mmol) are treated with DMF (300 μL) and H2O (3 μl). The vial is flushed and then sealed under argon and heated to 120° C. overnight. At RT, the vial is treated with NaOH (1M, 0.5 mL) and i-PrOAc (0.5 mL), and the upper organic layer is purified via strong cation exchange chromatography. The base-eluted solution is concentrated to dryness and treated with HCl (conc., 0.1 mL) and shaken at RT for 1 h and then at 100° C. for an additional 1 h. The reaction is concentrated to dryness under a stream of nitrogen and treated with adamantan-1-yl-methylamine hydrochloride (8.1 mg, 0.040 mmol), TEA (10% (v/v) ACN, 200 μL), and 2-chloro-1,3-dimethyl-4,5-dihydro-3H-imidazolium chloride (0.2 M ACN, 200 μL, 0.040 mmol). The reaction is sealed under nitrogen and shaken at RT for 1 h. NaOH (1M, 0.5 mL) and i-PrOAc (0.5 mL) are added, and the upper organic layer is removed and concentrated to dryness. The residue is purified via silica gel chromatography using EtOAc followed by TEA/MeOH/EtOAc (2.5:2.5:95% v/v/v) to afford the title compound. NMR (400 MHz, CDCl3) δ 1.59 (m, 6H), 1.64 (m, 3H), 1.72 (m, 3H), 1.99 (m, 3H), 3.18 (d, J=6.4, 2H), 7.68 (d, J=1.2, 1H), 7.83 (d, J=6.8, 1H), 7.99 (d, J=1.6, 1H), 8.12 (bs, 1H), 8.58 (d, J=6.8, 1H).

Aufarbeitung

  1. customThe vial is flushed
  2. customsealed under argon
  3. additionAt RT, the vial is treated with NaOH (1M, 0.5 mL) and i-PrOAc (0.5 mL)
  4. customthe upper organic layer is purified via strong cation exchange chromatography
  5. concentrationThe base-eluted solution is concentrated to dryness
  6. additiontreated with HCl (conc., 0.1 mL)
  7. waitat 100° C. for an additional 1 h
  8. concentrationThe reaction is concentrated to dryness under a stream of nitrogen
  9. customThe reaction is sealed under nitrogen
  10. stirringshaken at RT for 1 h
  11. customthe upper organic layer is removed
  12. concentrationconcentrated to dryness
  13. customThe residue is purified via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7347959fe1b54d0dbd44bd91dc69f56b
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431593B2

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