7a-Furyl or thienyl-substituted steroid compounds
The present invention involves intermediates, including a 7α-substituted steroid (II), and processes which are used to prepare eplerenone, a useful pharmaceutical agent.
1 - 23 . (canceled)
24 . A compound having the structure:
wherein:
X 1 is selected from the group consisting of —S— and —O—;
R b is selected from the group consisting of —H and C 1 -C 4 alkyl;
R c is selected from the group consisting of —H, C 1 -C 4 alkyl, —F, —Cl, —Br, and —I;
R d is selected from the group consisting of —H and C 1 -C 10 alkyl;
R 9 taken together with R 11a form a second bond between the carbon atoms to which they are attached; or R 9 and R 11a are taken together with —O— to form an epoxide; or R 9 is —H and R 11a is —OH; and
R 17a taken together with R 17b form=O; or R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH; or R 17a is α-C≡C—H and R 17b is β-OH; or R 17a is —C≡C—CH 2 —OH and R 17b is H; or R 17a and R 17b are taken together with the attached carbon atom to form:
25 . The compound of claim 24 wherein X 1 is —O—, and R b is —H.
26 . The compound of claim 24 wherein:
X 1 is —O—;
R b is —H;
R c is —H;
R d is C 1 -C 10 alkyl; and
R 17a taken together with R 17b form=O; or
R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH; or
R 17a and R 17b are taken together with the attached carbon atom to form:
27 . The compound of claim 26 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
28 . The compound of claim 26 wherein R 17a taken together with R 17b form=O.
29 . The compound of claim 26 wherein R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH.
30 . The compound of claim 26 wherein R d is methyl.
31 . The compound of claim 26 wherein R d is tert-butyl.
32 . The compound of claim 26 wherein R 9 taken together with R 11a form a second bond between the carbon atoms to which they are attached.
33 . The compound of claim 32 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
34 . The compound of claim 32 wherein R d is methyl.
35 . The compound of claim 32 wherein R d is tert-butyl.
36 . The compound of claim 26 wherein R 9 and R 11a are taken together with —O— to form an epoxide.
37 . The compound of claim 36 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
38 . The compound of claim 36 wherein R d is methyl.
39 . The compound of claim 37 wherein R d is tert-butyl.
40 . The compound of claim 26 wherein R 9 is —H and R 11a is —OH.
41 . The compound of claim 40 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
42 . The compound of claim 40 wherein R d is methyl.
43 . The compound of claim 40 wherein R d is tert-butyl.
44 . The compound of claim 24 having the structure:
45 . The compound of claim 24 having the structure:
46 . The compound of claim 24 having the structure:
47 . The compound of claim 24 having the structure:
48 . The compound of claim 24 having the structure:
49 . The compound of claim 25 wherein:
X 1 is —O—;
R b is —H;
R c is selected from the group consisting of C 1 -C 4 alkyl, —F, —Cl, —Br, and —I;
R d is —H; and
R 17a taken together with R 17b form=O; or
R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH; or
R 17a and R 17b are taken together with the attached carbon atom to form:
50 . The compound of claim 49 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
51 . The compound of claim 49 wherein R 17a taken together with R 17b form=O.
52 . The compound of claim 49 wherein R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH.
53 . The compound of claim 49 wherein R c is methyl.
54 . The compound of claim 49 wherein R c is —Br.
55 . The compound of claim 49 wherein R 9 taken together with R 11a form a second bond between the carbon atoms to which they are attached.
56 . The compound of claim 55 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
57 . The compound of claim 56 wherein R c is methyl.
58 . The compound of claim 56 wherein R c is —Br.
59 . The compound of claim 49 wherein R 9 and R 11 a are taken together with —O— to form an epoxide.
60 . The compound of claim 49 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
61 . The compound of claim 60 wherein R c is methyl.
62 . The compound of claim 60 wherein R c is —Br.
63 . The compound of claim 49 wherein R 9 is —H and R 11a is —OH.
64 . The compound of claim 63 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
65 . The compound of claim 63 wherein R c is methyl.
66 . The compound of claim 63 wherein R c is —Br.
67 . The compound of claim 24 having the structure:
68 . The compound of claim 24 having the structure:
69 . A composition comprising:
compound having the structure:
wherein:
X 1 is selected from the group consisting of —S— and —O—;
R b is selected from the group consisting of —H and C 1 -C 4 alkyl;
R c is selected from the group consisting of —H, C 1 -C 4 alkyl, —F, —Cl, —Br, and —I;
R d is selected from the group consisting of —H and C 1 -C 10 alkyl;
R 9 taken together with R 11a form a second bond between the carbon atoms to which they are attached; or R 9 and R 11a are taken together with —O— to form an epoxide; or R 9 is —H and R 11a is —OH; and
R 17a taken together with R 17b form=O; or R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH; or R 17a is α-C≡C—H and R 17b is β-OH; or R 17a is —C≡C—CH 2 —OH and R 17b is H; or R 17a and R 17b are taken together with the attached carbon atom to form:
70 . The composition of claim 69 wherein X 1 is —O—, and R b is —H.
71 . The composition of claim 69 wherein:
X 1 is —O—;
R b is —H;
R c is —H;
R d is C 1 -C 10 alkyl; and
R 17a taken together with R 17b form=O; or
R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH; or
R 17a and R 17b are taken together with the attached carbon atom to form:
72 . The composition of claim 71 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
73 . The composition of claim 71 wherein R 17a taken together with R 17b form ═O.
74 . The composition of claim 71 wherein R 17a is α-CH 2 —CH 2 —CO—O— − and R 17b is β-OH.
75 . The composition of claim 71 wherein R d is methyl.
76 . The composition of claim 71 wherein R d is tert-butyl.
77 . The composition of claim 71 wherein R 9 taken together with R 11a form a second bond between the carbon atoms to which they are attached.
78 . The composition of claim 77 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
79 . The composition of claim 77 wherein R d methyl.
80 . The composition of claim 77 wherein R d is tert-butyl.
81 . The composition of claim 71 wherein R 9 and R 11a are taken together with —O— to form an epoxide.
82 . The composition of claim 81 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
83 . The composition of claim 81 wherein R d is methyl.
84 . The composition of claim 82 wherein R d is tert-butyl.
85 . The composition of claim 71 wherein R 9 is —H and R 11a is —OH.
86 . The composition of claim 85 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
87 . The composition of claim 85 wherein R d is methyl.
88 . The composition of claim 85 wherein R d is tert-butyl.
89 . The composition of claim 69 having the structure:
90 . The composition of claim 69 having the structure:
91 . The composition of claim 69 having the structure:
92 . The composition of claim 69 having the structure:
93 . The composition of claim 69 having the structure:
94 . The composition of claim 70 wherein:
X 1 is —O—;
R b is —H;
R c is selected from the group consisting of C 1 -C 4 alkyl, —F, —Cl, —Br, and —I;
R d is —H; and
R 17a taken together with R 17b form═O; or
R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH; or
R 17a and R 17b are taken together with the attached carbon atom to form:
95 . The composition of claim 94 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
96 . The composition of claim 94 wherein R 17a taken together with R 17b form ═O.
97 . The composition of claim 94 wherein R 17a is α-CH 2 —CH 2 —CO—O − and R 17b is β-OH.
98 . The composition of claim 94 wherein R c is methyl.
99 . The composition of claim 94 wherein R c is —Br.
100 . The composition of claim 94 wherein R 9 taken together with R 11a form a second bond between the carbon atoms to which they are attached.
101 . The composition of claim 100 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
102 . The composition of claim 101 wherein R c is methyl.
103 . The composition of claim 101 wherein R c is —Br.
104 . The composition of claim 94 wherein R 9 and R 11a are taken together with —O— to form an epoxide.
105 . The composition of claim 94 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
106 . The composition of claim 105 wherein R c is methyl.
107 . The composition of claim 105 wherein R c is —Br.
108 . The composition of claim 94 wherein R 9 is —H and R 11a is —OH.
109 . The composition of claim 108 wherein R 17a and R 17b are taken together with the attached carbon atom to form:
110 . The composition of claim 108 wherein R c is methyl.
111 . The composition of claim 108 wherein R c is —Br.
112 . The composition of claim 69 having the structure:
113 . The composition of claim 69 having the structure: