N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → 4-(4-Cyano-2-Methoxyphenyl)-6-Fluoro-N-(Thiazol-2-Yl)-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonamide

HRID 528611

Reaktionsgleichung

Reaktionsgleichung von HRID 528611
COC1C=CC(C[NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:26]([C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][O:37][C:36]3[CH:40]=[C:41]([S:45](Cl)(=[O:47])=[O:46])[C:42]([F:44])=[CH:43][C:35]2=3)=[C:30]([O:49][CH3:50])[CH:29]=1)#[N:27]>C1COCC1>[C:26]([C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][O:37][C:36]3[CH:40]=[C:41]([S:45]([NH:8][C:9]4[S:10][CH:11]=[CH:12][N:13]=4)(=[O:47])=[O:46])[C:42]([F:44])=[CH:43][C:35]2=3)=[C:30]([O:49][CH3:50])[CH:29]=1)#[N:27]

Komponenten

5

Edukt 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 89761803HCID 89761803, Verbindung

Produkt 1

HCID 897616074-(4-Cyano-2-Methoxyphenyl)-6-Fluoro-N-(Thiazol-2-Yl)-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a vial charged with N-(4-methoxybenzyl)thiazol-2-amine (0.055 g, 0.250 mmol) was added THF (0.743 ml) and the mixture cooled in an ice water bath prior to the addition of lithium bis(trimethylsilyl)amide, 1.0M solution in tetrahydrofuran (0.273 ml, 0.273 mmol), faster than dropwise. After 15 mins of stirring a solution of 4-(4-cyano-2-methoxyphenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (0.087 g, 0.227 mmol) in THF (0.6 ml) was added dropwise, then washed with 0.2 ml THF and added. The mixture was stirred for 1 hr (ice melt) providing a brown solution and product as the primary species according to LC-MS (m/z=567) with consumption of starting material. The solution was added to ice, the mixture diluted with EtOAc and extracted with water and EtOAc. The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. To the crude material, a light yellow/brown foam (115 mg) was added DCM (5 ml) and TFA (1.5 ml) and the mixture stirred at room temp for 60 mins affording about 85% conversion to desired product. Stirring for another hr did not afford further conversion. Additional TFA (1 ml) was added and stirring at room temperature continued. After another hr LC-MS indicated no further conversion.

Aufarbeitung

  1. temperaturethe mixture cooled in an ice water bath
  2. additionwas added dropwise
  3. washwashed with 0.2 ml THF
  4. additionadded
  5. customproviding a brown solution and product as the primary species
  6. customaccording to LC-MS (m/z=567) with consumption of starting material
  7. additionThe solution was added to ice
  8. additionthe mixture diluted with EtOAc
  9. extractionextracted with water and EtOAc
  10. dry with materialThe combined organics were dried with Na2SO4
  11. filtrationfiltered
  12. customdried under reduced pressure
  13. additionTo the crude material, a light yellow/brown foam (115 mg) was added DCM (5 ml) and TFA (1.5 ml)
  14. stirringthe mixture stirred at room temp for 60 mins

Quellen und Nachweise

ORD-Eintrag
ord-5f6d2d8fa976496eafde0cb3b05df604
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346798B2

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