Azetidine → methyl 7-{2-[(Z)-3-azetidin-1-yl-prop-1-enyl]-4-fluorobenzene-sulfonylamino}-4H-furo[2,3-c]chromene-6-carboxylate

HRID 1778405Notes

Reaction equation

HRID 1778405 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:40]([CH:43]([CH3:45])C)[CH2:41]C)(C)C.CS(Cl)(=O)=O.N1CCC1>C(Cl)Cl.C1(C)C=CC=CC=1>[N:40]1([CH2:35]/[CH:34]=[CH:33]\[C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=2[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:9])=[O:10])[CH2:41][CH2:45][CH2:43]1

Participants

7

Reactant 4

HCID 10422AzetidineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 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 66693981methyl 7-{2-[(Z)-3-azetidin-1-yl-prop-1-enyl]-4-fluorobenzene-sulfonylamino}-4H-furo[2,3-c]chromene-6-carboxylateYield 20.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

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, 0.150 g) in DCM (10 mL) was added N,N-di-isopropyl-N-ethylamine (0.112 g) and methanesulfonyl chloride (0.040 g). The mixture was stirred at room temperature for 15 minutes. A solution of azetidine (0.083 g) in toluene (2 mL) was added and the reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with DCM, washed with water and brine, 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%. The resultant product was triturated with diethyl ether to give methyl 7-{2-[(Z)-3-azetidin-1-yl-prop-1-enyl]-4-fluorobenzene-sulfonylamino}-4H-furo[2,3-c]chromene-6-carboxylate (0.030 g) as a white powder.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 1 hour
  2. washwashed with water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10%
  8. customThe resultant product was triturated with diethyl ether

Sources & evidence

ORD record
ord-25ec9b4b478b4984b679da6f6c5f9295
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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