Intermediates and processes in the preparation of 5-oxygenated HMG-COA reductase inhibitors

Claim 2

A compound of structural formula (3): ##STR29## wherein: Z is Cl or Br; T is H, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trimethylsilyl, triethylsilyl, triiospropylsilyl, or tetrahydropyranyl; R 1 is selected from: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkylS(O) n in which n is 0 to 2, (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (3) C 1-10 alkoxy; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) substituted C 3-8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkoxycarbonyl, (k) C 1-5 acyloxy, (l) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (7) phenyl; (8) substituted phenyl in which the substituents are X and Y; (9) amino; (10) C 1-5 alkylamino; (11) di(C 1- 5 alkyl)amino; (12) phenylamino; (13) substituted phenylamino in which the substituents are X and Y; (14) phenyl C 1-10 alkylamino; (15) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y; (16) a member selected from (a) piperidinyl, (b) pyrrolidinyl, (c) piperazinyl, (d) morpholinyl, and (e) thiomorpholinyl; and (17) R 5 S in which R 5 is selected from (a) C 1-10 alkyl, (b) phenyl, and (c) substituted phenyl in which the substituents are X and Y; R' 4 is CH 3 , CH 2 TO or H; X and Y are independently selected from: (a) OH, (b) halogen, (c) trifluoromethyl, (d) C 1-3 alkoxy, (e) C 1-3 alkylcarbonyloxy, (f) phenylcarbonyloxy, (g) C 1-3 alkoxycarbonyl, (h) phenyloxycarbonyl, (i) hydrogen; (j) C 1-5 alkyl.

Claim 3

A compound according to claim 1 wherein: Z is Br; R 1 is selected from: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, and (i) oxo; (3) C 3-8 cycloalkyl; (4) substituted C 3-8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl, (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy (iv) C 1-5 acyloxy, (v) C 1-5 alkoxycarabonyl, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y, and (viii) oxo, (c) halogen, (d) hydroxy, (e) C 1-10 alkoxy, (f) C 1-5 alkoxycarbonyl, (g) C 1-5 acyloxy, (h) phenyl, (i) substituted phenyl in which the substituents are X and Y; (5) phenylamino; (6) substituted phenylamino in which the substituents are X and Y; (7) phenylC 1-10 alkylamino; and (8) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y; X and Y are independently selected from (a) OH, (b) F, (c) trifluoromethyl, (d) C 1-3 alkoxy, (e) hydrogen; (f) C 1-5 alkyl.

Claim 4

A compound according to claim 2 wherein: R 2 is C 1-10 alkyl; R' 4 is CH 3 or CH 2 TO.

Claim 5

A compound according to claim 3 selected from the group wherein: (a) R 1 is 2-methyl-2-butyl, R' 4 is CH 3 , T is tert-butyldimethylsilyl; (b) R 1 is 2-methyl-2-butyl, R' 4 is CH 2 TO, T is tert-butyldimethylsilyl; (c) R 1 is 2-butyl, R' 4 is CH 3 , T is tert-butyldimethylsilyl; (d) R 1 is 2-butyl, R' 4 is CH 2 TO, T is tert-butyldimethylsilyl,

Claim 6

A compound of structural formula (4-11): ##STR30## wherein: M is ##STR31## Z is Cl or Br; T is H, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trimethylsilyl, triethylsilyl, triiospropylsilyl, or tetrahydropyranyl; R 1 is selected from: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkylS(O) n in which n is 0 to 2, (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (3) C 1-10 alkoxy; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) substituted C 3-8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkocycarbonyl, (k) C 1-5 acyloxy, (l) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (7) phenyl; (8) substituted phenyl in which the substituents are X and Y; (9) amino; (10) C 1-5 alkylamino; (11) di(C 1-5 alkyl)amino; (12) phenylamino; (13) substituted phenylamino in which the substituents are X and Y; (14) phenyl C 1-10 alkylamino; (15) substituted phenylC 1-10 alkylamino in which the substituents are X and Y; (16) a member selected from (a) piperidinyl, (b) pyrrolidinyl, (c) piperazinyl, (d) morpholinyl, and (e) thiomorpholinyl; and (17) R 5 S in which R 5 is selected from (a) C 1-10 alkyl, (b) phenyl, and (c) substituted phenyl in which the substituents are X and Y; R' 4 is CH 3 , CH 2 TO or H; X and Y are independently selected from: (a) OH, (b) halogen, (c) trifluoromethyl, (d) C 1-3 alkoxy, (e) C 1-3 alkylcarbonyloxy, (f) phenylcarbonyloxy, (g) C 1-3 alkoxycarbonyl, (h) phenyloxycarbonyl, (i) hydrogen; (j) C 1-5 alkyl; a is a single bond or a double bond provided that when M is C-Z, a is a single bond.

Claim 7

A compound of structural formula (4-11): ##STR30## wherein: M is ##STR31## Z is Cl or Br; T is H, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trimethylsilyl, triethylsilyl, triiospropylsilyl, or tetrahydropyranyl; R 1 is selected from: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkylS(O) n in which n is 0 to 2, (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (3) C 1-10 alkoxy; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) substituted C 3-8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkocycarbonyl, (k) C 1-5 acyloxy, (l) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (7) phenyl; (8) substituted phenyl in which the substituents are X and Y; (9) amino; (10) C 1-5 alkylamino; (11) di(C 1-5 alkyl)amino; (12) phenylamino; (13) substituted phenylamino in which the substituents are X and Y; (14) phenyl C 1-10 alkylamino; (15) substituted phenylC 1-10 alkylamino in which the substituents are X and Y; (16) a member selected from (a) piperidinyl, (b) pyrrolidinyl, (c) piperazinyl, (d) morpholinyl, and (e) thiomorpholinyl; and (17) R 5 S in which R 5 is selected from (a) C 1-10 alkyl, (b) phenyl, and (c) substituted phenyl in which the substituents are X and Y; R' 4 is CH 3 , CH 2 TO or H; X and Y are independently selected from: (a) OH, (b) halogen, (c) trifluoromethyl, (d) C 1-3 alkoxy, (e) C 1-3 alkylcarbonyloxy, (f) phenylcarbonyloxy, (g) C 1-3 alkoxycarbonyl, (h) phenyloxycarbonyl, (i) hydrogen; (j) C 1-5 alkyl; a is a single bond or a double bond provided that when M is C-Z, a is a single bond.

Claim 8

A compound according to claim 5 wherein: M is ##STR32## Z is Br; R 1 is selected from: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituents(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, and (i) oxo; (3) C 3-8 cycloalkyl; (4) substituted C 3-8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl, (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy (iv) C 1-5 acyloxy, (v) C 1-5 alkoxycarbonyl, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y, and (viii) oxo, (c) halogen, (d) hydroxy, (e) C 1-10 alkoxy, (f) C 1-5 alkoxycarbonyl, (g) C 1-5 acyloxy, (h) phenyl, (i) substituted phenyl in which the substituents are X and Y; (5) phenylamino; (6) substituted phenylamino in which the substituents are X and Y; (7) phenylC 1-10 alkylamino; and (8) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y; X and Y are independently selected from (a) OH, (b) F, (c) trifluoromethyl, (d) C 1-3 alkoxy, (e) hydrogen; (f) C 1-5 alkyl.

Claim 9

A compound according to claim 6 wherein: R 1 is C 1-10 alkyl; R' 4 is CH 3 or CH 2 TO.

Claim 10

A compound according to claim 7 selected from the group wherein; (a) R 1 is 2-methyl-2-butyl, R' 4 is CH 3 , T is tert-butyldimethylsilyl; (b) R 1 is 2-methyl-2-butyl, R' 4 is CH 2 TO, T is tert-butyldimethylsilyl; (c) R 1 is 2-butyl, R' 4 is CH 3 , T is tert-butyldimethylsilyl; (d) R 1 is 2-butyl, R' 4 is CH 2 TO, T is tert-butyldimethylsilyl.