| 摘要 |
A process for the preparation of N-protected 6-(piperidin-4-ylcarbamoyl)piperidin-3-yl sulfonates of Formula (III): which comprises contacting a lactone of Formula (II): with an azacycloalkylamine of formula (II-Am): followed by contact with a sulfonyl halide of formula (II-Su): R4—SO2W (II-Su) in the presence of tertiary amine base, wherein PG1 and PG2 are amine protective groups; k, p and q are 0, 1, or 2, and W, R2, R3, R4, R5, R6, R7, R8, and R9 are defined herein. Additional embodiments add a series of process steps leading to the synthesis of 7-oxo-1,6-diazabicyclo[3.2.1]octanes suitable for use as β-lactamase inhibitors.; |
| 主权项 |
1. A process for preparing a compound of Formula III: which comprises:
(A) contacting a lactone of Formula II: with an azacycloalkylamine of formula II-Am: followed by contact with a sulfonyl halide of formula II-Su:
R4—SO2W (II-Su) in the presence of tertiary amine base to obtain a compound of Formula III wherein: PG1 is a first amine protecting group which forms with the amino nitrogen to which it is attached a carbamate, a benzylamine, or a sulfonamide; PG2 is a second amine protecting group selected from (i) carbamates and (ii) benzylamines; k is an integer equal to 0, 1, or 2; R2 and R3 are defined as follows:
(a) R2 is H, C1-6 alkyl, —O—C1-6 alkyl, —O—Si(—C1-6 alkyl)3, or —O—Si(—C1-6 alkyl)(-phenyl)2,
and each R3 is H or C1-6 alkyl; or(b) alternatively and with the proviso that k is 1 or 2, R2 and the R3 adjacent to R2 together with the carbon atoms to which each is attached form C5-7 cycloalkyl which is optionally substituted with from 1 to 3 substituents each of which is independently C1-6 alkyl, —O—C1-6 alkyl, —O—Si(—C1-6 alkyl)3, or —O—Si(—C1-6 alkyl)(-phenyl)2; and any other R3 is H or C1-6 alkyl; R4 is
(1) phenyl optionally substituted with from 1 to 3 substituents each of which is independently C1-4 alkyl, C1-4 haloalkyl, —O—C1-4 alkyl, —O—C1-4 haloalkyl, Cl, Br, F, or NO2;(2) C1-4 alkyl; or(3) C1-4 haloalkyl; R5 is H or C1-3 alkyl; R6 and R8 are independently H, C1-3 alkyl, O—C1-3 alkyl, or N(—C1-3 alkyl)2; each R7 and R9 is independently H or C1-6 alkyl W is halogen; p is 0, 1, or 2; q is 0, 1, or 2; and p+q=0, 1, 2, or 3. |
