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 1778409Notes

Reaction equation

HRID 1778409 reaction equation
[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

Participants

6

Reactant 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×

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

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.

Workup

  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%

Sources & evidence

ORD record
ord-a3676ee265ed48528c98104d2c6de3b8
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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