Tetrahydrofuran → 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528553

Reaktionsgleichung

Reaktionsgleichung von HRID 528553
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22](Cl)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2.[S:26]1[CH:30]=[C:29]([NH2:31])[N:28]=[CH:27]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CCOC(C)=O.CCCCCCC>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([NH:31][C:29]3[N:28]=[CH:27][S:26][CH:30]=3)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 14009640Thiazol-4-amineHCID 897618504-(2-Bromo-4-(Trifluoromethyl)Phenyl)-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonyl Chloride2×

Produkt 1

HCID 717116224-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideAusbeute 21,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21899848Ethylacetate heptaneLösungsmittel

Versuchsvorschrift

A round-bottom flask was charged with 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (INTERMEDIATE C, 299.84 mg, 0.657 mmol), thiazol-4-amine (79 mg, 0.788 mmol), and THF (3283 n1) to give a brown mixture. The flask was cooled in an ice-bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1379 μl, 1.379 mmol) was added dropwise over 30 s. After 30 min, the cooling bath was removed, and the mixture was allowed to warm to room temperature. The reaction mixture was quenched by the addition of aq. 1N hydrochloric acid and a small amount of brine and extracted with EtOAc (3×, emulsion). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography on a 40 g column with 0 to 10% MeOH/DCM. The desired product was repurified again by chromatography on a 40 g silica gel column, this time with 0 to 40% EtOAc/Heptane to give 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (73.1 mg, 0.140 mmol) as a cream-colored solid. 1H NMR (400 MHz, DMSO-d6) δ=10.88 (s, 1 H), 8.88 (d, J=2.2 Hz, 1 H), 8.20 (d, J=1.5 Hz, 1 H), 7.89 (dd, J=1.6, 8.5 Hz, 1 H), 7.73 (d, J=8.4 Hz, 1 H), 7.25 (d, J=2.2 Hz, 1 H), 7.16 (dd, J=2.2, 8.6 Hz, 1 H), 6.96 (d, J=2.2 Hz, 1 H), 6.22 (d, J=8.6 Hz, 1 H), 4.36 (d, J=15.8 Hz, 2 H), 3.78-3.63 (m, 2 H). m/z (ESI) 520.2 (M+H)+.

Aufarbeitung

  1. customto give a brown mixture
  2. temperatureThe flask was cooled in an ice-bath for 10 min
  3. customthe cooling bath was removed
  4. customThe reaction mixture was quenched by the addition of aq. 1N hydrochloric acid
  5. extractiona small amount of brine and extracted with EtOAc (3×, emulsion)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography on a 40 g column with 0 to 10% MeOH/DCM
  10. customThe desired product was repurified again by chromatography on a 40 g silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-1ac09a2860ae4ea5a85573bbc8961a96
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346798B2

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