Pyridine → 5-Chloro-N-methyl-N-[2-({[(1R)-1-phenylethyl]amino}methyl)-3,4-dihydro-2H-chromen-7-yl)thiophene-2-sulfonamide Hydrochloride

HRID 49466

Reaktionsgleichung

Reaktionsgleichung von HRID 49466
[CH3:1][NH:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]([CH2:13]O)[O:10]2)=[CH:5][CH:4]=1.N1C=CC=CC=1.[Cl:21][C:22]1[S:26][C:25]([S:27](Cl)(=[O:29])=[O:28])=[CH:24][CH:23]=1.C1(S(Cl)(=O)=O)C=CC=CC=1.[C:41]1([C@H:47]([NH2:49])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>ClC(Cl)C.O>[ClH:21].[Cl:21][C:22]1[S:26][C:25]([S:27]([N:2]([CH3:1])[C:3]2[CH:12]=[C:11]3[C:6]([CH2:7][CH2:8][CH:9]([CH2:13][NH:49][C@@H:47]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)[CH3:48])[O:10]3)=[CH:5][CH:4]=2)(=[O:29])=[O:28])=[CH:24][CH:23]=1

Komponenten

8

Edukt 5

HCID 1049Pyridine2×HCID 7369Benzenesulfonyl chlorideHCID 6431891-Phenethylamine, (+)-HCID 27339255-Chlorothiophene-2-sulfonyl chlorideHCID 11480975[7-(Methylamino)-3,4-dihydro-2H-chromen-2-yl]methanol

Produkt 1

HCID 698857065-Chloro-N-methyl-N-[2-({[(1R)-1-phenylethyl]amino}methyl)-3,4-dihydro-2H-chromen-7-yl)thiophene-2-sulfonamide HydrochlorideAusbeute 92,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 63651,1-DichloroethaneLösungsmittel

Versuchsvorschrift

A solution of [7-(methylamino)-3,4-dihydro-2H-chromen-2-yl]methanol (386 mg; 2.00 mmol) and pyridine (0.8 mL; 10 mmol) in dichloroethane is treated with 5-chlorothiophene-2-sulfonyl chloride (477 mg, 2.2 mmol), stirred at ambient temperature for 1 h, treated with pyridine (0.8 mL; 10 mmol) and benzenesulfonyl chloride (1.0 mL; 8 mmol), heated at 60° C. with stirring for 2 h, poured into water and extracted with ethyl ether. The combined extracts are washed successively with dilute aqueous HCl and saturated aqueous solution of sodium bicarbonate, dried over MgSO4 and concentrated in vacuo. The resultant residue is treated with (1R)-1-phenyl-1-ethanamine (2.6 mL; 20 mmol) at 100° C. with stirring for 2 h, cooled to ambient temperature, poured into water and extracted with ethyl ether. The combined extracts are washed with brine, dried over MgSO4 and concentrated in vacuo. The resultant residue is purified by column chromatography (silica gel, 1% methanol in methylene chloride) to afford the free base of the title product as a clear oil (525 mg, 55% yield). Treatment with an ethereal solution of HCl gives the title product as a white crystalline powder, mp 236° C., identified by NMR and mass spectral analyses.

Aufarbeitung

  1. temperatureheated at 60° C.
  2. stirringwith stirring for 2 h
  3. extractionextracted with ethyl ether
  4. washThe combined extracts are washed successively with dilute aqueous HCl and saturated aqueous solution of sodium bicarbonate
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. stirringwith stirring for 2 h
  8. temperaturecooled to ambient temperature
  9. extractionextracted with ethyl ether
  10. washThe combined extracts are washed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe resultant residue is purified by column chromatography (silica gel, 1% methanol in methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-b2f86432e9db4f38926c46c6921657aa
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06706757B2

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