Sodium Carbonate → N2-(2-chloro-5-(3-hydroxyazetidine-1-carbonyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

HRID 1190568Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1190568
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]=[C:23]([C:25]([N:27]5[CH2:30][CH:29]([OH:31])[CH2:28]5)=[O:26])[CH:22]=[CH:21][C:20]=4[Cl:32])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:33]=1.CC1(C)C2[C:56](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:55]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:76][NH2:77].Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:32][C:20]1[CH:21]=[CH:22][C:23]([C:25]([N:27]2[CH2:30][CH:29]([OH:31])[CH2:28]2)=[O:26])=[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:56]([NH:77][CH3:76])=[O:55])=[CH:33][C:6]=3[O:7][CH2:8][CH2:9][C:10]=2[CH:14]=1)=[O:16]

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6364545Methylamine hydrochlorideHCID 58204028HCID 58204028, Verbindung

Produkt 1

HCID 58204264N2-(2-chloro-5-(3-hydroxyazetidine-1-carbonyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamideAusbeute 462,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A suspension of 8-bromo-N-(2-chloro-5-(3-hydroxyazetidine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (500 mg, 0.91 mmol), Pd(OAc)2 (10 mg, 0.046 mmol), Xantphos (53 mg, 0.091 mmol), MeNH2.HCl (92 mg, 1.37 mmol) and Na2CO3 (289 mg, 2.73 mmol) in toluene (5 mL) and DMF (5 mL) was heated at 80° C. under atmosphere of CO from balloon for overnight. Then it was filtrated and concentrated, the crude product was purified by flash column chromatography on silica gel (DCM: MeOH=20:1 as eluted solvent) to give a white solid which was washed with MeOH and dried to give 360 (221.5 mg, yield 46%). 1H NMR (DMSO, 400 MHz): δ8.43 (m, 1H, NH), 7.87-7.43 (m, 6H, ArH), 6.65 (s, 1H, ═CH), 5.52 (d, J=6.4 Hz, 1H, OH), 4.48-2.75 (m, 15H). LC-MS: (ESI, m/z)=526 [M+H]+

Aufarbeitung

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. customthe crude product was purified by flash column chromatography on silica gel (DCM: MeOH=20:1 as eluted solvent)
  4. customto give a white solid which
  5. washwas washed with MeOH
  6. customdried

Quellen und Nachweise

ORD-Eintrag
ord-968b23f94fe4482e88cd0811a9a5fbac
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673952B2

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