Cesium carbonate → HCID 89761997, Verbindung

HRID 528619

Reaktionsgleichung

Reaktionsgleichung von HRID 528619
COC1C=CC(C[N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=CC=1.Br[C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[O:38][CH3:39])[C:33]#[N:34].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:33]([C:32]1[CH:31]=[CH:30][C:37]([O:38][CH3:39])=[C:36]([N:20]2[CH2:19][CH2:18][O:17][C:16]3[CH:21]=[C:12]([S:9]([NH:8][C:22]4[S:23][CH:24]=[CH:25][N:26]=4)(=[O:10])=[O:11])[CH:13]=[CH:14][C:15]2=3)[CH:35]=1)#[N:34]

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7360493-Bromo-4-methoxybenzonitrileHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2×

Produkt 1

HCID 89761997HCID 89761997, VerbindungAusbeute 70,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Versuchsvorschrift

A vial was charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIate M) (80 mg, 0.192 mmol), 3-bromo-4-methoxybenzonitrile (81 mg, 0.383 mmol), Xantphos (22.17 mg, 0.038 mmol), Pd2(dba)3 (17.55 mg, 0.019 mmol), and cesium carbonate (187 mg, 0.575 mmol). The vessel was flushed with Ar (g), then 1,4-dioxane (1916 μl) was added. The vessel was sealed and placed in a 100° C. heating bath for 20 h. The mixture was filtered through celite with the aid of EtOAc. The filtrate was concentrated, and the residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 4 h, mixture was diluted with MeOH, then concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-5% MeOH/DCM). The material this obtained was further purified by chromatography on silica gel (12-g Redi-Sep Gold column, 50-100% EtOAc/Heptane). The resulting solid was taken up in EtOAc, sonicated, and filtered. The collected solid was washed with EtOAc (2×), dried under a stream of N2 (g), then dried under vacuum to give 4-(5-cyano-2-methoxyphenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (58 mg, 0.135 mmol, 70.6% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ=12.55 (br. s., 1 H), 7.92-7.77 (m, 2 H), 7.34 (d, J=8.5 Hz, 1 H), 7.22 (d, J=4.5 Hz, 1 H), 7.16-7.06 (m, 2 H), 6.78 (d, J=4.5 Hz, 1 H), 6.21 (d, J=8.4 Hz, 1 H), 4.30 (br. s., 2 H), 3.85 (s, 3 H), 3.63 (br. s., 2 H); m/z (ESI) 429.2 (M+H)+.

Aufarbeitung

  1. customThe vessel was flushed with Ar (g)
  2. addition1,4-dioxane (1916 μl) was added
  3. customThe vessel was sealed
  4. customplaced in a 100° C.
  5. temperatureheating bath for 20 h
  6. filtrationThe mixture was filtered through celite with the aid of EtOAc
  7. concentrationThe filtrate was concentrated
  8. dissolutionthe residue was dissolved in DCM (1 mL)
  9. additionmixture was diluted with MeOH
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-5% MeOH/DCM)
  12. customThe material this obtained was further purified by chromatography on silica gel (12-g Redi-Sep Gold column, 50-100% EtOAc/Heptane)
  13. customsonicated
  14. filtrationfiltered
  15. washThe collected solid was washed with EtOAc (2×)
  16. dry with materialdried under a stream of N2 (g)
  17. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-53ffb7d7e98443368aed2bd8b4ff979d
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346798B2

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