Methanesulfonyl chloride → methyl 7-{4-fluoro-2-[(Z)-3-(3-acetoxyazetidin-1-yl)-prop-1-enyl]-benzenesulfonylamino]-4H-furo[2,3-c]chromene-6-carboxylate

HRID 1778409Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1778409
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C:16]2[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]3[C:19]([C:20]4[CH:32]=[CH:31][O:30][C:21]=4[CH2:22][O:23]3)=[CH:18][CH:17]=2)C(OC)=O)(=[O:10])=[O:9])=[C:4](/[CH:33]=[CH:34]\[CH2:35]O)[CH:3]=1.C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.FC(F)(F)C(O)=O.[NH:58]1[CH2:61][CH:60]([O:62][C:63](=[O:65])[CH3:64])[CH2:59]1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:16]2[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]3[C:19]([C:20]4[CH:32]=[CH:31][O:30][C:21]=4[CH2:22][O:23]3)=[CH:18][CH:17]=2)(=[O:10])=[O:9])=[C:4](/[CH:33]=[CH:34]\[CH2:35][N:58]2[CH2:61][CH:60]([O:62][C:63](=[O:65])[CH3:64])[CH2:59]2)[CH:3]=1

Komponenten

6

Edukt 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 666857643-Azetidinol, 3-acetate, 2,2,2-trifluoroacetate (1:1)HCID 68093356methyl 7-{N-[4-fluoro-2-((Z)-3-hydroxy-prop-1-enyl)-benzenesulfonyl]-N-(methoxycarbonyl)amino}-4H-furo[2,3-c]chromene-6-carboxylate2×

Produkt 1

HCID 66692991methyl 7-{4-fluoro-2-[(Z)-3-(3-acetoxyazetidin-1-yl)-prop-1-enyl]-benzenesulfonylamino]-4H-furo[2,3-c]chromene-6-carboxylateAusbeute 40,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

To a suspension of methyl 7-{N-[4-fluoro-2-((Z)-3-hydroxy-prop-1-enyl)-benzenesulfonyl]-N-(methoxycarbonyl)amino}-4H-furo[2,3-c]chromene-6-carboxylate (Intermediate 92, 0.220 g) in DCM (10 mL) was added N,N-di-isopropyl-N-ethylamine (1.10 g) and methanesulfonyl chloride (0.059 g). The mixture was stirred at room temperature for 1.5 hours. A solution of acetic acid azetidin-3-yl ester trifluoroacetate salt (1.40 g) in DCM (5 mL) was added and the resultant mixture was stirred at room temperature for 30 minutes. The mixture was diluted with DCM and washed with water, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10% to give methyl 7-{4-fluoro-2-[(Z)-3-(3-acetoxyazetidin-1-yl)-prop-1-enyl]-benzenesulfonylamino]-4H-furo[2,3-c]chromene-6-carboxylate (0.095 g) as a white foam.

Aufarbeitung

  1. washwashed with water
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by chromatography on silica
  6. washeluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10%

Quellen und Nachweise

ORD-Eintrag
ord-a3676ee265ed48528c98104d2c6de3b8
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266896B2

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