Sodium Carbonate → HCID 58204160, Verbindung

HRID 708131Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 708131
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)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:55][C:37]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:76][S:77]([CH2:80][CH2:81][NH2:82])(=[O:79])=[O:78].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:37]([NH:82][CH2:81][CH2:80][S:77]([CH3:76])(=[O:79])=[O:78])=[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 17749886Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)HCID 58204028HCID 58204028, Verbindung

Produkt 1

HCID 58204160HCID 58204160, VerbindungAusbeute 458,1 %

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 (400 mg, 0.73 mmol), Pd(OAc)2 (8 mg, 0.037 mmol), Xantphos (42 mg, 0.073 mmol), MeSO2(CH2)2NH2.HCl (175 mg, 1.095 mmol) and Na2CO3 (232 mg, 2.19 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 384 (206.7 mg, yield 46%). 1H NMR (DMSO, 400 MHz): δ8.74 (t, J=5.6 Hz, 1H, NH), 7.87-6.61 (m, 7H, ArH), 5.75 (d, J=6.0 Hz, 1H, OH), 4.48-2.99 (m, 19H). LC-MS: (ESI, m/z)=618 [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-2e6544da2e37469cbdb4c0112d6b85e0
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09175009B2

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