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 1778409ノート

反応式

HRID 1778409 の反応式
[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

参加物

6

反応物 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 回

生成物 1

HCID 66692991methyl 7-{4-fluoro-2-[(Z)-3-(3-acetoxyazetidin-1-yl)-prop-1-enyl]-benzenesulfonylamino]-4H-furo[2,3-c]chromene-6-carboxylate収率 40.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

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.

後処理

  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%

出典と根拠

ORDレコード
ord-a3676ee265ed48528c98104d2c6de3b8
出典データセット
uspto-grants-2016_02
特許番号
US09266896B2

反応ノート

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