Ethanol → 4-Methoxy-5''-methyl-5'-[5-(prop-1-yn-1-yl)pyridin-3-yl]dispiro[cyclohexane-1,2'-[1]benzofuran-3',2''-imidazol]-4''-amine

HRID 539353

Reaktionsgleichung

Reaktionsgleichung von HRID 539353
[C:1]([C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[N:8][CH:9]=1)#[C:2][CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:20]1[CH:21]=[CH:22][C:23]2[O:34][C:33]3([CH2:39][CH2:38][CH:37]([O:40][CH3:41])[CH2:36][CH2:35]3)[C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]=2[CH:25]=1.CCO>COCCOC.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:41][O:40][CH:37]1[CH2:38][CH2:39][C:33]2([C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]3[CH:25]=[C:20]([C:6]4[CH:7]=[N:8][CH:9]=[C:4]([C:1]#[C:2][CH3:3])[CH:5]=4)[CH:21]=[CH:22][C:23]=3[O:34]2)[CH2:35][CH2:36]1

Komponenten

8

Edukt 4

HCID 702EthanolHCID 10796Cesium carbonateHCID 574164825-(1-Propynyl)pyridine-3-boronic Acid (contains varying amounts of Anhydride)2×HCID 679795525'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amine

Produkt 1

HCID 679793924-Methoxy-5''-methyl-5'-[5-(prop-1-yn-1-yl)pyridin-3-yl]dispiro[cyclohexane-1,2'-[1]benzofuran-3',2''-imidazol]-4''-amineAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

5-(Prop-1-ynyl)pyridin-3-ylboronic acid (Intermediate 15, 57.4 mg, 0.36 mmol), (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (9.79 mg, 0.01 mmol), cesium carbonate (233 mg, 0.71 mmol) and 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine (Example 29, 90 mg, 0.24 mmol) were dissolved in a 6:3:1 mixture of DME:EtOH:water (2 mL) and heated at 150° C. in a microwave reactor for 15 min. The mixture was concentrated and the residue was partitioned between EtOAc (7 mL) and sat. aq. NaHCO3 (5 mL). The layers were separated and the organic layer was dried over MgSO4 and concentrated. Purification of the crude product by preparative chromatography afforded 41 mg of the title compound (42% yield). 1 H NMR (500 MHz, DMSO-d6) δ ppm 1.22 (m, 1 H), 1.46 (m, 3 H), 1.81 (m, 2 H), 1.98 (m, 2 H), 2.09 (s, 3 H), 2.21 (s, 3 H), 3.10 (m, 1 H), 3.22 (s, 3 H), 6.70 (s, 2 H), 6.95 (d, 1 H), 6.99 (d, 1 H), 7.56 (d, 1 H), 7.91 (t, 1 H), 8.47 (d, 1 H), 8.67 (d, 1 H); MS (APCI+) m/z 415 [M+H]+.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between EtOAc (7 mL) and sat. aq. NaHCO3 (5 mL)
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude product by preparative chromatography

Quellen und Nachweise

ORD-Eintrag
ord-eecb33f106ac43c6910a720013a126cb
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865911B2

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