Sodium Carbonate → N2-(2-chloro-5-((R)-2-hydroxypropylcarbamoyl)phenyl)-N2-methyl-N8-(2-(methylsulfonyl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

HRID 2385907Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2385907
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](=[O:31])[NH:26][CH2:27][C@H:28]([OH:30])[CH3:29])[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](=[O:31])[NH:26][CH2:27][C@H:28]([OH:30])[CH3:29])=[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 67050592HCID 67050592, Verbindung

Produkt 1

HCID 67050604N2-(2-chloro-5-((R)-2-hydroxypropylcarbamoyl)phenyl)-N2-methyl-N8-(2-(methylsulfonyl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamideAusbeute 179,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A suspension of 8-bromo-N-(2-chloro-5-((R)-2-hydroxypropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (500 mg, 0.91 mmol), Pd(OAc)2 (10 mg, 0.045 mmol), Xantphos (53 mg, 0.091 mmol), MeSO2(CH2)2NH2.HCl (218 mg, 1.36 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 overnight. Then it was filtrated and concentrated, the crude product was purified by pre-TLC (DCM: MeOH=10:1 as eluted solvent) to give 387 (101.5 mg, yield 18%). 1H NMR (DMSO-d6, 400 MHz): δ8.73 (s, 1H, NH), 8.60 (s, 1H, NH), 8.12-7.45 (m, 6H, ArH), 6.61 (s, 1H, ═CH), 4.76 (d, J=4.8 Hz, 1H, OH), 4.20 (br s, 2H, CH2), 3.80-3.77 (m, 1H, CH), 3.67-2.98 (m, 14H, CH3, CH2), 1.06 (t, J=5.2 Hz, 3H, CH3). LC-MS: (ESI, m/z)=542 [M+Na]+

Aufarbeitung

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. customthe crude product was purified by pre-TLC (DCM: MeOH=10:1 as eluted solvent)

Quellen und Nachweise

ORD-Eintrag
ord-356d01c593c8494e8ed90301e95d3594
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08263633B2

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