Tetrahydrofuran → N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-Dicarboxamide

HRID 84493

Reaktionsgleichung

Reaktionsgleichung von HRID 84493
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([N:17]([C:19]4[CH:24]=[CH:23][C:22]([C:25]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)=[O:26])=[CH:21][C:20]=4[Cl:34])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:35]=1.[N:36]12[CH2:46]CCN=C1CCCC[CH2:37]2.[O:47]1CCCC1>CN.CCOC(C)=O.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].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]>[Cl:34][C:20]1[CH:21]=[C:22]([C:25]([N:27]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]2)=[O:26])[CH:23]=[CH:24][C:19]=1[N:17]([CH3:18])[C:15]([C:13]1[S:12][C:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:37]([NH:36][CH3:46])=[O:47])=[CH:35][C:6]=3[O:7][CH2:8][CH2:9][C:10]=2[CH:14]=1)=[O:16]

Komponenten

8

Edukt 3

HCID 8028Tetrahydrofuran2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 568343698-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

Produkt 1

HCID 44242776N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-DicarboxamideAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 98885Molybdenum carbonyl (Mo(CO)6)KatalysatorHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)KatalysatorHCID 6329MethylamineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a solution containing 8-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (0.075 g, 0.13 mmol) in tetrahydrofuran (1.50 mL, 18.5 mmol), 2.00 M of methylamine in tetrahydrofuran (0.196 mL) was added molybdenumhexacarbonyl (34.4 mg, 0.130 mmol), trans-di(mu-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium (II) (18.3 mg, 0.0196 mmol) then 1,8-diazabicyclo[5.4.0]undec-7-ene (9.75 uL, 0.0652 mmol) and capped quickly to prevent CO gas from escaping. The reaction mixture was heated in a microwave at 150° C. for 20 min. The reaction mixture was diluted with EtOAc then filtered thru celite. The combined organics were dried (Na2SO4), filtered and concentrated. The crude was submitted for RP HPLC to give 181 (yield 32%). MS: (ESI+) 553.2

Aufarbeitung

  1. filtrationthen filtered thru celite
  2. dry with materialThe combined organics were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-8309b2d57e7d4087b4811b7d5ede439e
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846762B2

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