Chroman derivatives
AssigneeMerck Patent GmbH
InventorsHeinz-Herman Bokel, Peter Mackert, Christoph Müramann, Nobert Schweickert
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Abstract
Chroman derivatives of the formula I in which R1 is acyl having 1-6 C atoms, —CO—R5 or an amino protective group, R2 is H or alkyl having 1-6 C atoms, R3, R4 in each case independently of one another are H, alkyl having 1-6 C atoms, CN, Hal or COOR2, R5 is phenyl which is unsubstituted or mono- or disubstituted by alkyl having 1-6 C atoms, OR2 or Hal, X is H, H or O, Hal is F, Cl, Br or I, and their salts, are suitable as intermediates in the synthesis of medicaments.
Claims28
A chroman compound of formula I
- in which
- R1 is acyl having 1-6 C atoms, —CO—R5 or an amino protective group,
- R2 is H or alkyl having 1-6 C atoms,
- R3, R4 in each case independently of one another are H, alkyl having 1-6 C atoms, CN, Hal or COOR2,
- R5 is phenyl which is unsubstituted or mono- or disubstituted by alkyl having 1-6 C atoms, OR2 or Hal,
- X is H, H or O,
- Hal is F, Cl, Br or I,
- or a physiologically acceptable salt thereof, wherein said compound is not N-(Chroman-2-ylmethyl)-cyclopropane carboxylic acid amide.
A method for the synthesis of (R)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chroman, or a salt thereof, comprising:
- a) hydrogenating with a chiral catalyst, a compound of the formula II
- in which
- R1 is acyl having 1-6 C atoms, —CO—R5 or an amino protective group,
- R2, R3 and R4 are H and X is O;
- b) crystalizing the enantiomeric (R) compound from the enantiomerically enriched mixture of (R) and (S) compounds thus obtained;
- c) reducing the enantiomeric (R) compound from b);
- d) removing the R1 radical from the (R) compound thus obtained to produce (R)-(chroman-2-ylmethyl)amine;
- and
- e) converting the (R)-(chroman-2-ylmethyl)amine to its an acid addition salt and reacting said acid addition salt to give (R)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chroman.
A method for the synthesis of (R)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chroman, or a salt thereof, comprising:
- a) hydrogenating with a chiral catalyst, a compound of the formula II
- in which
- R1 is acyl having 1-6 C atoms, —CO—R5 or an amino protective group,
- R2, R3 and R4 are H and X is O;
- b) reducing the enantiomerically enriched mixture of (R) and (S) compounds thus obtained;
- c) crystalizing the enantiomeric (R) compound from the enantiomerically enriched mixture of (R) and (S) compounds;
- d) removing the R1 radical from the (R) compound thus obtained to produce (R)-(chroman-2-ylmethyl)amine;
- and
- e) converting the (R)-(chroman-2-ylmethyl)amine to an acid addition salt and reacting said acid addition salt to give (R)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chroman.
A method for the synthesis of (R)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chroman, or a salt thereof, comprising:
- a) hydrogenating with a chrial catalyst, a compound of the formula II
- in which
- R1 is acyl having 1-6 C atoms, —CO—R5 or an amino protective group,
- R2, R3 and R4 are H and X is O;
- b) reducing the enantiomerically enriched mixture of (R) and (S) compounds thus obtained;
- c) removing the R1 radical from the compounds thus obtained;
- d) crystalizing the enantiomeric (R) compound from the enantiomerically enriched mixture of (R) and (S) compounds;
- and
- e) converting the enantiomeric (R) compound to an acid addition salt and reacting said acid addition salt to give (R)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chroman.
Dependencies are inferred from the claim text.