Phenethylamine → HCID 86703983, Verbindung

HRID 1773904Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1773904
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[CH3:24].[CH2:25]([CH2:32][NH2:33])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.N12CCCN=C1CCCCC2.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[O:63]1CCC[CH2:64]1>C(OCC)(=O)C.[OH-].[Na+].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[CH2:25]([CH2:32][NH:33][C:64]([C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]2)[C:3]=1[CH3:24])=[O:63])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Komponenten

10

Edukt 5

HCID 1001PhenethylamineHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 86703973HCID 86703973, Verbindung

Produkt 1

HCID 86703983HCID 86703983, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 98885Molybdenum carbonyl (Mo(CO)6)KatalysatorHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)KatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of 2-iodo-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 133) (80 mg, 0.18 mmole), N-benzylmethylamine (42 μL, 0.32 mmole), 1,8-diazabicyclo(5.4.0)undec-7-ene (24 μL, 0.16 mmole), trans-di-μ-acetatobis[2-(di-o-tolyl-phosphino)-benzyl]dipalladium(II) (11.5 mg), tri-tertbutylphosphonium tetrafluoroborate (8.5 mg) and molybdenum hexacarbonyl (30 mg, 0, 11 mmole) in tetrahydrofuran (1.5 mL) are introduced in a screw-capped vial. The vial is stirred at 130° C. for 1.5 hours, then cooled to room temperature, diluted with ethyl acetate and 1N aqueous sodium hydroxide. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. The residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 21% (B) to 31% (B) in 10 minutes) to afford pure 1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-2-carboxylic acid benzylmethylamide melting at 61° C.

Aufarbeitung

  1. additionare introduced in a screw-capped vial
  2. temperaturecooled to room temperature
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 21% (B) to 31% (B) in 10 minutes)

Quellen und Nachweise

ORD-Eintrag
ord-305ba2529b7045b0977949fcb374d6d3
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09255101B2

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