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US 2013/0096277 A1Published application
Processes and intermediates
AssigneeVertex Pharmaceuticals Incorporated
InventorGERALD J. TANOURY
Life of this patent
Estimating the term…
Abstract
A process for preparing enantioselectively a compound of formula I-1a or I-1b: over a compound of formulas I-2-I-7:
Claims77
A process for preparing enantioselectively a compound of formula I-1a or I-1b:
- over a compound of formulas I-2-I-7:
- comprising the step of carboxylating a compound of formulas II-a or II-b:
- in the presence of a compound of formula III:
- wherein:
- Ring A is a C3-12 cycloaliphatic ring;
- Ring B is a C3-12 heterocycloaliphatic ring containing additional 0 to 2 heteroatoms, each independently selected from O, N, and S, wherein ring B is optionally substituted with 0 to 4 groups, each independently selected from alkyl, halo, alkoxy, aryl, and hydroxy;
- R1 is H or a protecting group;
- R1a is a protecting group;
- R2 is H, a protecting group, or C1-12 aliphatic;
- and
- R3 is C1-12 aliphatic or a protecting group.
8 more elements
A process for preparing a compound of formula 10:
- wherein Z2 is H or a protecting group, and R2 is H, a protecting group, or C1-12 aliphatic, comprising the steps of:
- i) providing a compound of formula II-a:
- wherein R1a is a protecting group, and ring A is C3-12 cycloaliphatic;
- ii) forming a 2-anion of the compound of formula II-a in the presence of a compound of formula III:
- wherein R3 is C1-12 aliphatic or a protecting group;
- iii) treating the anion of step ii) with carbon dioxide to produce enantioselectively a compound of formula I-1a;
- and
- iv) reacting the compound of formula I-1a with a compound of formula 26,
- wherein Z3 is a protecting group, in the presence of a coupling reagent.
6 more elements
A process for preparing compounds of formula 4:
- comprising the steps of:
- i) reacting a compound of formula II-a with a base and CO2 in the presence of a compound of formula III to prepare a compound of formula I-1a;
- ii) reacting the a compound of formula I-1a with a compound of formula 26 in the presence of a coupling reagent to form a compound of formula 10;
- iii) removing Z2 from the compound of formula 10 to give a compound of formula 28:
- iv) reacting the compound of formula 28 with a compound of formula 29:
- in the presence of a coupling reagent to give a compound of formula 30:
- wherein Z is an amine protecting-group;
- v) removing the protecting group Z in the compound of formula 30 to give a compound of formula 31:
- vi) reacting the compound of formula 31 with a compound of formula 32:
- in the presence of a coupling reagent to give a compound of formula 33:
- vii) hydrolyzing the ester of the compound of formula 33 to give a compound of formula 34:
- viii) reacting the compound of formula 34 with a compound of formula 18:
- in the presence of a coupling reagent to give a compound of formula 35:
- ix) oxidizing the compound of formula 35 to give the compound of formula 4.
11 more elements
Dependencies are inferred from the claim text.