Cesium carbonate → 6-chloro-4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528598Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 528598
[Cl:1][C:2]1[C:11]([S:12]([N:15]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:16]2[S:17][CH:18]=[CH:19][N:20]=2)(=[O:14])=[O:13])=[CH:10][C:5]2[O:6][CH2:7][CH2:8][NH:9][C:4]=2[CH:3]=1.Br[C:31]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:32]=1[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]>[Cl:1][C:2]1[C:11]([S:12]([N:15]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:16]2[S:17][CH:18]=[CH:19][N:20]=2)(=[O:14])=[O:13])=[CH:10][C:5]2[O:6][CH2:7][CH2:8][N:9]([C:31]3[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:32]=3[C:33]#[N:34])[C:4]=2[CH:3]=1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 122239802-Bromo-5-(trifluoromethyl)benzonitrileHCID 897614296-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Produkt 1

HCID 897619626-chloro-4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Versuchsvorschrift

A 150-mL pressure vessel was charged with 6-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (2.32 g, 5.13 mmol), 2-bromo-5-(trifluoromethyl)benzonitrile (2.57 g, 10.27 mmol), Xantphos (0.594 g, 1.027 mmol), Pd2(dba)3 (0.470 g, 0.513 mmol), and cesium carbonate (5.02 g, 15.40 mmol). The vessel was flushed with Ar (g), then 1,4-dioxane (51.3 ml) was added. The vessel was sealed and placed in a 100° C. heating bath for 16 h. The mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (50-g Redi-Sep Gold column, 25-g silica gel loading column, 25-75% EtOAc/Heptane) to give 6-chloro-4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ=8.46 (d, J=2.1 Hz, 1 H), 8.15 (dd, J=1.8, 8.7 Hz, 1 H), 7.81 (d, J=8.5 Hz, 1 H), 7.50 (s, 1 H), 7.45 (d, J=3.6 Hz, 1 H), 7.32 (d, J=3.5 Hz, 1 H), 7.28-7.21 (m, 2 H), 6.90-6.78 (m, 3 H), 5.17 (s, 2 H), 4.40-4.34 (m, 2 H), 3.91-3.85 (m, 2 H), 3.71 (s, 3 H); m/z (ESI) 621.0 (M+H)+.

Aufarbeitung

  1. customThe vessel was flushed with Ar (g)
  2. addition1,4-dioxane (51.3 ml) was added
  3. customThe vessel was sealed
  4. customplaced in a 100° C.
  5. temperatureheating bath for 16 h
  6. additiondiluted with water
  7. extractionextracted with EtOAc (3×)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by chromatography on silica gel (50-g Redi-Sep Gold column, 25-g silica gel loading column, 25-75% EtOAc/Heptane)

Quellen und Nachweise

ORD-Eintrag
ord-3dcb643472de4acb8e54a5c4429a804f
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346798B2

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