US5248797A
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US
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Method for the production of 9-amino-6-demethyl-6-deoxytetracycline
Assignee: Wyeth Holdings LLC
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Filing: 1992-08-13
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Granted: 1993-09-28
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Expires: 2012-08-13
Abstract
Abstract The invention relates to a novel method for producing [4S-(4alpha, 12aalpha)]-9-amino-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide, hereinafter called 9-amino-6-demethyl-6-deoxytetracycline, which compound is a valuable intermediate for synthesis of tetracyclines.
Inventors
- 👤 Phaik-Eng Sum
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 20:34
CPC Classifications
C; C07; C07C; C07C231/00; C07C231/12; C07C237/00; C07C237/24; C07C237/26; C07C2603/00; C07C2603/02; C07C2603/40; C07C2603/42; C07C2603/44; C07C2603/46
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
129 words
A process for producing 9-Amino-6-de-methyl-6-deoxytetracycline mineral acid salt which comprises: (a) reacting 6-demethyl-6-deoxytetracycline, in cold concentrated mineral acid, with a halogenating agent at a temperature from 0° C. to about 20° C. and recovering 7-halogen-6-demethyl-6-deoxytetracycline mineral acid salt by filtration or recrystallization; and (b) reacting the 7-halogen-6-demethyl-6-deoxytetracycline mineral acid salt, in a cold concentrated mineral acid, with a slight molar excess of a nitrating reagent at temperature ranges from -15° C to +15° C. and recovering 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt by filtration or recrystallization; and (c) reducing, at room temperature, the 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt, in a solvent, with Group VIII metal catalysts, their salts or rare metal oxides at between 1 and 40 psi, isolating the product by dilution in an alcohol and recovering 9-amino-6-demethyl-6-deoxytetracycline mineral acid salt.
Claim 2
Dependent Claim
129 words
A process for producing 9-Amino-6-de-methyl-6-deoxytetracycline mineral acid salt which comprises: (a) reacting 6-demethyl-6-deoxytetracycline, in cold concentrated mineral acid, with a halogenating agent at a temperature from 0° C. to about 20° C. and recovering 7-halogen-6-demethyl-6-deoxytetracycline mineral acid salt by filtration or recrystallization; and (b) reacting the 7-halogen-6-demethyl-6-deoxytetracycline mineral acid salt, in a cold concentrated mineral acid, with a slight molar excess of a nitrating reagent at temperature ranges from -15° C to +15° C. and recovering 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt by filtration or recrystallization; and (c) reducing, at room temperature, the 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt, in a solvent, with Group VIII metal catalysts, their salts or rare metal oxides at between 1 and 40 psi, isolating the product by dilution in an alcohol and recovering 9-amino-6-demethyl-6-deoxytetracycline mineral acid salt.
Claim 3
Dependent Claim
18 words
The process of claim 1 wherein said halogenating agent comprises bromine, N-chlorosuccinimide, N-bromosuccinimide, iodine monochloride or benzyltrimethylammonium dichloroiodate.
Claim 4
Dependent Claim
11 words
The process of claim 2 wherein said halogenating agent comprises N-bromosuccinimide.
Claim 5
Dependent Claim
14 words
The process of claim 1 wherein said concentrated mineral acid comprises concentrated sulfuric acid.
Claim 6
Dependent Claim
16 words
The process of claim 1 wherein said temperature for step a is maintained at 0° C.
Claim 7
Dependent Claim
15 words
The process of claim 1 wherein said 7-halogen-6-demethyl-6-deoxytetracycline mineral acid salt is recovered by filtration.
Claim 8
Dependent Claim
22 words
The process of claim 1 wherein said 7-halogen-6-demethyl-6-deoxytetracycline mineral acid salt is recrystallized from a mixture of 2-methoxy-ethanol, methanol and diethyl ether.
Claim 9
Dependent Claim
18 words
The process of claim 1 wherein said nitrating reagent comprises a "mixed acid" or a metal nitrate salt.
Claim 10
Dependent Claim
22 words
The process of claim 8 wherein said "mixed acid" comprises 1.1 to 1.2 equivalents of 10% nitric acid in concentrated sulfuric acid.
Claim 11
Dependent Claim
14 words
The process of claim 1 wherein said mineral acid comprises cold concentrated sulfuric acid.
Claim 12
Dependent Claim
16 words
The process of claim 1 wherein said temperature for step b is maintained at 0° C.
Claim 13
Dependent Claim
15 words
The process of claim 1 wherein said 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt is recovered by filtration.
Claim 14
Dependent Claim
43 words
The process of claim 1 wherein said Group VIII metal catalyst, their salts or rare earth oxides comprises 10-30% by weight of Pt on activated carbon, Pd on activated carbon, rhodium on activated carbon, ruthenium on activated carbon or iridium on activated carbon.
Claim 15
Dependent Claim
23 words
The process of claim 13 wherein said Group VIII metal catalyst comprises 10 to 30% by weight of 10% palladium on activated carbon.
Claim 16
Dependent Claim
32 words
The process of claim 1 wherein said solvent for step c is a 5:1 mixture of 2-methoxyethanol:lN sulfuric or hydrochloric acid, methanol:lN sulfuric or hydrochloric acid or ethanol:lN sulfuric or hydro-chloric acid.
Claim 17
Dependent Claim
16 words
The process of claim 15 wherein said solvent comprises a 5:1 mixture of 2-methoxyethanol:lN sulfuric acid.
Claim 18
Dependent Claim
17 words
The process of claim 1 wherein said 9-Amino-6-demethyl-6-deoxytetracycline mineral acid salt is isolated by dilution with isopropanol.
Claim 19
Dependent Claim
15 words
The process of claim 1 wherein said 9-Amino-6-demethyl-6-deoxytetracycline mineral acid salt is recovered by filtration.
Claim 20
Dependent Claim
115 words
A process for producing 9-Amino-6-demethyl-6-deoxytetracycline mineral acid salt which comprises: (a) reacting 6-demethyl-6-deoxytetracycline, in cold concentrated mineral acid, with a halogenating agent at a temperature from 0° C. to about 20° C. followed by the addition of a slight molar excess of a solid metal nitrate salt or a "mixed acid" at temperature ranges of from -15° C. to +15° C., diluting with a solvent and recovering 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt; and (b) reducing, at room temperature, the 7-halogen-9nitro-6-demethyl-6-deoxytetracycline mineral acid salt, in a solvent, with Group VIII metal catalysts, their salts or rare metal oxides at between 1 and 40 psi, isolating the product with an alcohol and recovering 9-amino-6- demethyl-6-deoxytetracycline mineral acid salt.
Claim 21
Dependent Claim
115 words
A process for producing 9-Amino-6-demethyl-6-deoxytetracycline mineral acid salt which comprises: (a) reacting 6-demethyl-6-deoxytetracycline, in cold concentrated mineral acid, with a halogenating agent at a temperature from 0° C. to about 20° C. followed by the addition of a slight molar excess of a solid metal nitrate salt or a "mixed acid" at temperature ranges of from -15° C. to +15° C., diluting with a solvent and recovering 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt; and (b) reducing, at room temperature, the 7-halogen-9nitro-6-demethyl-6-deoxytetracycline mineral acid salt, in a solvent, with Group VIII metal catalysts, their salts or rare metal oxides at between 1 and 40 psi, isolating the product with an alcohol and recovering 9-amino-6- demethyl-6-deoxytetracycline mineral acid salt.
Claim 22
Dependent Claim
18 words
The process of claim 19 wherein said halogenating agent comprises bromine, N-bromosuccinimide, N-chlorosuccinimide, iodine monochloride or benzyltrimethylammonium dichloroiodate.
Claim 23
Dependent Claim
11 words
The process of claim 20 wherein said halogenating agent is N-bromosuccinimide.
Claim 24
Dependent Claim
14 words
The process of claim 19 wherein said concentrated mineral acid comprises concentrated sulfuric acid.
Claim 25
Dependent Claim
16 words
The process of claim 19 wherein said temperature for step a is maintained at 0° C.
Claim 26
Dependent Claim
18 words
The process of claim 19 wherein said metal nitrate salt comprises a 10% molar excess of potassium nitrate.
Claim 27
Dependent Claim
22 words
The process of claim 19 wherein said "mixed acid" comprises 1.1 to 1.2 equivalents of 10% nitric acid in concentrated sulfuric acid.
Claim 28
Dependent Claim
18 words
The process of claim 19 wherein said 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt is recovered by dilution with diethyl ether.
Claim 29
Dependent Claim
35 words
The process of claim 26 wherein said 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt is purified by trituration with alcohols, dilution of the filtrate with diethyl ether and filtration to collect the resulting pure 7-halogen-9-nitro-6-demethyl-6-deoxytetracycline mineral acid salt.
Claim 30
Dependent Claim
14 words
The process of claim 27 wherein said alcohols comprises methyl alcohol and isopropyl alcohol.
Claim 31
Dependent Claim
43 words
The process of claim 19 wherein said Group VIII metal catalyst, their salts or rare earth oxides comprises 10-30% by weight of Pt on activated carbon, Pd on activated carbon, rhodium on activated carbon, ruthenium on activated carbon or iridium on activated carbon.
Claim 32
Dependent Claim
23 words
The process of claim 29 wherein said Group VIII metal catalyst comprises 10 to 30% by weight of 10% palladium on activated carbon.
Claim 33
Dependent Claim
32 words
The process of claim 19 wherein said solvent for step c is a 5:1 mixture of 2-methoxyethanol:1N sulfuric or hydrochloric acid, methanol:lN sulfuric or hydrochloric acid or ethanol:lN sulfuric or hydrochlor acid.
Claim 34
Dependent Claim
16 words
The process of claim 31 wherein said solvent comprises a 5:1 mixture of 2-methoxyethanol:lN sulfuric acid.
Claim 35
Dependent Claim
16 words
The process of claim 19 wherein said 9-Amino-6-demethyl-6-deoxytetracycline mineral acid salt isolated by dilution with isopropanol.
Claim 36
Dependent Claim
15 words
The process of claim 32 wherein said 9-Amino-6-demethyl-6-deoxytetracycline mineral acid salt is recovered by filtration.
References Cited (Backward Citations)
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1996-09-27 | 1997-03-29 | 1997-09-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-09-27 | 2001-03-29 | 2001-09-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-09-27 | 2005-03-29 | 2005-09-28 | $7700.00 | Window Closed / Lapsed |