US4440933A
Expired / Lapsed
US
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Process for preparing 1,2,5-thiadiazoles
Assignee: Bristol Myers Co
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Filing: 1983-03-16
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Granted: 1984-04-03
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Expires: 2003-03-16
Abstract
Abstract Histamine H 2 -receptor antagonists of the formula ##STR1## wherein A, m, Z, n and R 1 are as defined herein, and their nontoxic pharmaceutically acceptable salts, hydrates and solvates are novel anti-ulcer agents which are prepared by ring closure of a substituted ethanediimidamide of the formula ##STR2## with a compound of the formula R--S--R in which R is as defined herein.
Inventors
- 👤 Thomas A. Montzka
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 06:13
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/44; C07D209/48; C07D407/00; C07D407/02; C07D407/12; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/62; C07D213/63; C07D213/64; C07D285/00; C07D285/01; C07D285/02; C07D285/04; C07D285/10; C07D295/00; C07D295/04; C07D295/08; C07D295/096; C07D333/00; C07D333/02; C07D333/04; C07D333/06; C07D333/14; C07D333/20; C07D417/00; C07D417/02; C07D417/12
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
316 words
A process for the preparation of a compound of the formula ##STR39## wherein R 1 is hydrogen, (lower)alkyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, allyl, propargyl, ##STR40## in which p is 1 or 2, R 2 and R 3 each are independently hydrogen, (lower)alkyl, (lower)alkoxy or halogen, and, when R 2 is hydrogen, R 3 also may be trifluoromethyl, or R 2 and R 3 , taken together, may be methylenedioxy, and R 4 is hydrogen, (lower)alkyl or (lower)alkoxy; m is an integer of from 0 to 2 inclusive; n is an integer of from 2 to 5 inclusive; Z is oxygen, sulfur or methylene; and A is ##STR41## in which R 5 is hydrogen, (lower)alkyl or (lower)alkoxy, q is an integer of from 1 to 4 inclusive and R 6 and R 7 each are independently (lower)alkyl, (lower)alkoxy(lower)alkyl in which the (lower)alkoxy moiety is at least two carbon atoms removed from the nitrogen atom, or phenyl(lower)alkyl, and, when R 6 is hydrogen, R 7 also may be cyclo(lower)alkyl, or R 6 and R 7 , taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, dimethylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, dimethylpiperidino, N-methylpiperazino, 1,2,3,6-tetrahydropyridyl, homopiperidino, heptamethyleneimino, octamethyleneimino, 3-azabicyclo[3.2.2]non-3-yl or 3-pyrrolino; and nontoxic, pharmaceutically acceptable salts, hydrates and solvates thereof; which process comprises reacting a substituted ethanediimidamide of the formula ##STR42## in which A, m, Z, n and R 1 are as described above, with a compound of the formula R--S--R VII in which the two R groups are the same and may be ##STR43## in which X and Y are independently hydrogen, (lower)alkyl, (lower)alkoxy, chloro, bromo, nitro, methanesulfonyl, benzenesulfonyl, cyclo(lower)alkyl or phenyl, X' and Y' are independently hydrogen, (lower)alkyl or phenyl, X" and Y" are independently hydrogen or (lower)alkyl and X"' and Y"' are independently (lower)alkyl or phenyl, in a non-reactive organic solvent, at a temperature of from about 0° C. to about 100° C.
Claim 2
Dependent Claim
316 words
A process for the preparation of a compound of the formula ##STR39## wherein R 1 is hydrogen, (lower)alkyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, allyl, propargyl, ##STR40## in which p is 1 or 2, R 2 and R 3 each are independently hydrogen, (lower)alkyl, (lower)alkoxy or halogen, and, when R 2 is hydrogen, R 3 also may be trifluoromethyl, or R 2 and R 3 , taken together, may be methylenedioxy, and R 4 is hydrogen, (lower)alkyl or (lower)alkoxy; m is an integer of from 0 to 2 inclusive; n is an integer of from 2 to 5 inclusive; Z is oxygen, sulfur or methylene; and A is ##STR41## in which R 5 is hydrogen, (lower)alkyl or (lower)alkoxy, q is an integer of from 1 to 4 inclusive and R 6 and R 7 each are independently (lower)alkyl, (lower)alkoxy(lower)alkyl in which the (lower)alkoxy moiety is at least two carbon atoms removed from the nitrogen atom, or phenyl(lower)alkyl, and, when R 6 is hydrogen, R 7 also may be cyclo(lower)alkyl, or R 6 and R 7 , taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, dimethylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, dimethylpiperidino, N-methylpiperazino, 1,2,3,6-tetrahydropyridyl, homopiperidino, heptamethyleneimino, octamethyleneimino, 3-azabicyclo[3.2.2]non-3-yl or 3-pyrrolino; and nontoxic, pharmaceutically acceptable salts, hydrates and solvates thereof; which process comprises reacting a substituted ethanediimidamide of the formula ##STR42## in which A, m, Z, n and R 1 are as described above, with a compound of the formula R--S--R VII in which the two R groups are the same and may be ##STR43## in which X and Y are independently hydrogen, (lower)alkyl, (lower)alkoxy, chloro, bromo, nitro, methanesulfonyl, benzenesulfonyl, cyclo(lower)alkyl or phenyl, X' and Y' are independently hydrogen, (lower)alkyl or phenyl, X" and Y" are independently hydrogen or (lower)alkyl and X"' and Y"' are independently (lower)alkyl or phenyl, in a non-reactive organic solvent, at a temperature of from about 0° C. to about 100° C.
Claim 3
Dependent Claim
156 words
A process of claim 1 for the preparation of a compound of the formula ##STR44## wherein R 1 is hydrogen or (lower)alkyl, m is 0 or 1, n is 2 or 3, Z is oxygen or sulfur and A is ##STR45## in which R 5 is hydrogen or methyl, and R 6 and R 7 each are independently methyl or ethyl, or when taken together with the nitrogen to which they are attached, R 6 and R 7 represent a pyrrolidino or piperidino ring; or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof; which process comprises reacting a substituted ethanediimidamide of the formula ##STR46## in which A, m, Z, n and R 1 are as described above, with a compound of the formula R--S--R VII in which the two R groups are the same and may be ##STR47## in a non-reactive organic solvent, at a temperature of from about 0° C. to about 100° C.
Claim 4
Dependent Claim
108 words
A process of claim 1 for the preparation of a compound of the formula ##STR48## wherein R 1 is hydrogen or methyl, and R 6 and R 7 each are methyl or, when taken together with the nitrogen atom to which they are attached, R 6 and R 7 represent a pyrrolidino or piperidino ring; or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof; which process comprises reacting a compound of the formula ##STR49## in which R 1 , R 6 and R 7 are as defined above, with N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 5
Dependent Claim
95 words
A process of claim 1 for the preparation of a compound of the formula ##STR50## wherein R 1 and R 5 each are independently hydrogen or methyl, and R 6 and R 7 each are independently methyl or ethyl; or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof; which process comprises reacting a compound of the formula ##STR51## in which R 1 , R 5 , R 6 and R 7 are as defined above, with N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 6
Dependent Claim
95 words
A process of claim 1 for the preparation of a compound of the formula ##STR52## wherein R 1 and R 5 each are independently hydrogen or methyl, and R 6 and R 7 each are independently methyl or ethyl; or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof; which process comprises reacting a compound of the formula ##STR53## in which R 1 , R 5 , R 6 and R 7 are as defined above, with N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 7
Dependent Claim
114 words
A process of claim 1 for the preparation of a compound of the formula ##STR54## wherein R 1 and R 5 each are independently hydrogen or methyl, and R 6 and R 7 each are independently methyl or ethyl, or, when taken together with the nitrogen to which they are attached, R 6 and R 7 represent piperidino; or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof; which process comprises reacting a compound of the formula ##STR55## in which R 1 , R 5 , R 6 and R 7 are as defined above, with N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 8
Dependent Claim
45 words
A process for the preparation of 3-amino-4-[3-(3-piperidinomethylphenoxy)propylamino]-1,2,5-thiadiazole, or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof, which comprises reacting N-[3-(3-piperidinomethylphenoxy)-propyl]ethanediimidamide with about an equimolar amount of N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 9
Dependent Claim
45 words
A process for the preparation of 3-amino-4-[3-(3-piperidinomethylphenoxy)propylamino]-1,2,5-thiadiazole, or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof, which comprises reacting N-[3-(3-piperidinomethylphenoxy)-propyl]ethanediimidamide with about an equimolar amount of N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 10
Dependent Claim
45 words
A process for the preparation of 3-amino-4-[3-(3-pyrrolidinomethylphenoxy)propylamino]-1,2,5-thiadiazole, or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof, which comprises reacting N-[3-(3-pyrrolidinomethylphenoxy)propyl]ethanediimidamide with about an equimolar amount of N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 11
Dependent Claim
45 words
A process for the preparation of 3-amino-4-[3-(3-pyrrolidinomethylphenoxy)propylamino]-1,2,5-thiadiazole, or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof, which comprises reacting N-[3-(3-pyrrolidinomethylphenoxy)propyl]ethanediimidamide with about an equimolar amount of N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 12
Dependent Claim
45 words
A process for the preparation of 3-amino-4-[3-(4-piperidinomethyl-2-pyridyloxy)propylamino]-1,2,5-thiadiazole, or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof, which comprises reacting N-[3-(4-piperidinomethyl-2-pyridyloxy)propyl]ethanediimidamide with about an equimolar amount of N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
Claim 13
Dependent Claim
45 words
A process for the preparation of 3-amino-4-[3-(4-piperidinomethyl-2-pyridyloxy)propylamino]-1,2,5-thiadiazole, or a nontoxic pharmaceutically acceptable salt, hydrate or solvate thereof, which comprises reacting N-[3-(4-piperidinomethyl-2-pyridyloxy)propyl]ethanediimidamide with about an equimolar amount of N,N'-thiobisphthalimide in a non-reactive organic solvent at a temperature of from about 10° C. to about 50° C.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-04-03 | 1987-10-03 | 1988-04-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-04-03 | 1991-10-03 | 1992-04-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-04-03 | 1995-10-03 | 1996-04-03 | $7700.00 | Window Closed / Lapsed |