Chiral synthesis of n--1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides
AssigneeBayer Intellectual Property GmbH
InventorsPeter Fey, Agathe Christine Mayer
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Abstract
The present invention relates to a novel enantioselective method of preparing (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-5 methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide, to novel intermediate compounds, and to the use of said novel intermediate compounds for the preparation of said (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide.
Claims28
A compound selected from:
- 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonyl bromide (S)-10-Br:
- 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonyl bromide (R)-10-Br:
- potassium 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropane-sulfonate (S)-7′:
- potassium 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropane-sulfonate (R)-7′:
- Butyl 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonate (S)-6:
- Butyl 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonate (R)-6:
- Butyl 1-[(2S)-2,3-dihydroxypropyl]cyclopropanesulfonate (S)-5:
- Butyl 1-[(2R)-2,3-dihydroxypropyl]cyclopropanesulfonate (R)-5:
- Butyl 1-[(2S)-oxiran-2-ylmethyl]cyclopropanesulfonate (S)-4:
- Butyl 1-[(2R)-oxiran-2-ylmethyl]cyclopropanesulfonate (R)-4:
- Butyl 1-[(2S)-3-chloro-2-hydroxypropyl]cyclopropanesulfonate (S)-3:
- Butyl 1-[(2R)-3-chloro-2-hydroxypropyl]cyclopropanesulfonate (R)-3:
- Butyl 1-[(2S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl]cyclopropane-sulfonate (S)-9a:
- Butyl 1-[(2R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl]cyclopropane-sulfonate (R)-9a:
- Butyl 1-[(2S)-2-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)propyl]cyclopropane sulfonate (S)-9b:
- and
- Butyl 1-[(2R)-2-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)propyl]cyclopropane sulfonate (R)-9b:
A method of preparing a compound of formula (S)-14:
- comprising:
- i)
- reacting a compound of formula (S)-10:
- with a compound of formula (12):
- in the presence of a bromide, optionally in the presence of a base, and optionally in a solvent,
- thereby providing a reaction mixture containing a compound of formula (S)-13:
- and, then,
- ii)
- adding an aqueous mineral acid to said reaction mixture containing a compound of formula (S)-13,
- thereby providing a compound of formula (S)-14.
A method of preparing a compound of formula (S)-14:
- comprising:
- i)
- reacting a compound of formula (S)-10-Br:
- with a compound of formula (12):
- optionally in the presence of a base, and optionally in a solvent,
- thereby providing a reaction mixture containing a compound of formula (S)-13:
- and, then,
- ii)
- adding an aqueous mineral acid to said reaction mixture containing a compound of formula (S)-13,
- thereby providing a compound of formula (S)-14.
A method of preparing a compound of formula (S)-14:
- comprising
- the step of adding an aqueous mineral acid to a compound of formula (S)-13:
- thereby providing a compound of formula (S)-14.
A method of preparing a compound of formula (S)-14:
- comprising
- reacting a compound of formula (S)-6:
- with a sodium alkoxide, optionally in a solvent,
- thereby providing a compound of formula (S)-7:
(canceled)
Dependencies are inferred from the claim text.