56610-72-1

Basic information

• Product Name: 7-MAC
• Synonyms: (6R,7S)-Benzhydryl 7-aMino-7-Methoxy-3-(((1-Methyl-1H-tetrazol-5-yl)thio)Methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;Methoxy Cephalosporins;5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylicacid, 7-aMino-7-Methoxy-3-[[(1-Methyl-1H-tetrazol-5-yl)thio]Methyl]-8-oxo-,diphenylMethyl ester, (6R,7S)-;benzhydryl (6R,7S)-7-amino-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;7 beta - amino - 7 alpha - methoxy - 3 - (1 - methyl - 1 h - tetrazolium sulfur - 5 - methyl) - - 5-8 - oxygen generation sulfur - 1 - mixed nitrogen double loop [4.2.0] essien - 2 - methyl - 2 - formic acid diphenyl;7-MAC;7-ACA-3-MTT-7-MO;7-MAC OR 7-AMAC(INTERMEDIATE OF CEFMINOX)
• CAS NO: 56610-72-1
• Molecular Formula: C₂₄H₂₄N₆O₄S₂
• Molecular Weight: 524.61516
• EINECS: 1308068-626-2
• Product Categories: Pharmaceutical raw material;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 56610-72-1.mol
• Article Data: 7

Chemical Properties

• Melting Point: 120°C(lit.)
• Boiling Point: 743.2 °C at 760 mmHg
• Flash Point: 403.2 °C
• Appearance: /
• Density: 1.5 g/cm³
• Vapor Pressure: 5.89E-22mmHg at 25°C
• Refractive Index: 1.733
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Chloroform (Slightly), Methanol (Slightly, Heated)
• PKA: 3.39±0.60(Predicted)
• CAS DataBase Reference: 7-MAC(CAS DataBase Reference)
• NIST Chemistry Reference: 7-MAC(56610-72-1)
• EPA Substance Registry System: 7-MAC(56610-72-1)

Safety Data

• Hazardous Substances Data: 56610-72-1(Hazardous Substances Data)

Usage

Chemical Properties

Pale Yellow Solid

Uses

7-MAC is a 7α-methoxycephalosporin derivative used as an intermediate in the preparation of Cefmetazole (C242850) and other semi-synthetic antibiotics.

InChI:InChI=1/C24H24N6O4S2/c1-29-23(26-27-28-29)36-14-17-13-35-22-24(25,33-2)21(32)30(22)18(17)20(31)34-19(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,19,22H,13-14,25H2,1-2H3/t22-,24+/m1/s1

Synthetic route

C31H28N6O5S2 → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
With pyridine; bis(trichloromethyl) carbonate In dichloromethane at -25 - 5℃; for 3h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;	94.1%

(6R-cis)-7-methoxy-3-<<(1-methyl-1-H-tetrazol-5-yl)thio>methyl>-8-oxo<(phenylacetyl)amino>-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester (64278-77-9) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
With pyridine; phosphorus pentachloride In methanol; dichloromethane at -30 - 5℃; for 4h; Reagent/catalyst;	91%
Stage #1: (6R-cis)-7-methoxy-3-<<(1-methyl-1-H-tetrazol-5-yl)thio>methyl>-8-oxo<(phenylacetyl)amino>-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester With pyridine; phosphorus pentachloride In dichloromethane at 5 - 8℃; for 2h; Stage #2: In methanol at -30 - -10℃; for 2h;	90%

2-amino-benzenethiol (137-07-5) + (6R,7S)-7-[1-Chloro-but-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-10-5) → 2-propylbenzo[d]thiazole (17229-76-4) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + (6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-09-2)

Conditions	Yield
With pyridine In dichloromethane for 1.5h; Ambient temperature;	A 45% B 15% C 23%

(6R,7S)-7-[1-Chloro-but-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-10-5) → 2-propylbenzo[d]thiazole (17229-76-4) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + (6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-09-2)

Conditions	Yield
With pyridine; 2-amino-benzenethiol In dichloromethane for 1.5h; Ambient temperature;	A 45% B 15% C 23%

2-amino-benzenethiol (137-07-5) + (6R,7S)-7-[5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-1-chloro-pent-(Z)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 5-Benzothiazol-2-yl-2-tert-butoxycarbonylamino-pentanoic acid benzhydryl ester

Conditions	Yield
With pyridine In dichloromethane Ambient temperature;	A 25% B 35%

(6R,7S)-7-[5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-1-chloro-pent-(Z)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 5-Benzothiazol-2-yl-2-tert-butoxycarbonylamino-pentanoic acid benzhydryl ester

Conditions	Yield
With pyridine; 2-amino-benzenethiol In dichloromethane Ambient temperature;	A 25% B 35%

(6R)-7t-(3,5-di-tert-butyl-4-hydroxy-benzylideneamino)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (56023-19-9) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
With girard's reagent T In methanol; ethyl acetate Ambient temperature;

(6R,7S)-7-(5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-pentanoylamino)-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (57793-21-2) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: phosgene-pyridine / CH2Cl2 / Ambient temperature 2: 25 percent / pyridine / CH2Cl2 / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: phosgene-pyridine / CH2Cl2 / Ambient temperature 2: 25 percent / pyridine, o-amino-benzenethiol / CH2Cl2 / Ambient temperature View Scheme

(6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-09-2) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: phosgene-pyridine / CH2Cl2 / 3 h / Ambient temperature 2: 15 percent / pyridine, o-amino-benzenethiol / CH2Cl2 / 1.5 h / Ambient temperature View Scheme

7β-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>ceph-3-em-4-oic acid benzhydryl ester (53090-86-1) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) benzene, (ii) PbO2, 1,2-dichloroethane, (iii) /BRN= 1098229/, benzene 2: Girard T / ethyl acetate; methanol / Ambient temperature View Scheme

7-Aminocephalosporanic acid (957-68-6) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: boron trifluoride diethyl etherate / acetonitrile / 2.5 h / 50 °C 2.1: sodium hydrogencarbonate / water; acetone / 3.67 h / 0 - 20 °C 3.1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 5.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 6.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 7.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 7.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 7 steps 1: boron trifluoride diethyl etherate / acetonitrile / 2.5 h / 50 °C 2: sodium hydrogencarbonate / acetone; water / 3 h / 0 - 25 °C 3: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 4: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 5: phosphorus trichloride / dichloromethane / 3 h / Reflux 6: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 7: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

(6R,7R)-7-amino-3-[(1H-1-methyltetrazol-5-yl)thio]methylceph-3-em-4-carboxylic acid (24209-38-9) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: sodium hydrogencarbonate / water; acetone / 3.67 h / 0 - 20 °C 2.1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 4.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 5.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 6.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 6.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 6 steps 1: sodium hydrogencarbonate / acetone; water / 3 h / 0 - 25 °C 2: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 3: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 4: phosphorus trichloride / dichloromethane / 3 h / Reflux 5: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 6: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

(6R,7R)-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-aza-bicyclo [4.2.0]oct-2-ene-2-carboxylic acid (47653-82-7) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 3.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 4.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 5.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 5.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 5 steps 1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 2: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 3: phosphorus trichloride / dichloromethane / 3 h / Reflux 4: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 5: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

(6R,7R)-benzhydryl-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 2.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 3.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 4.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 4.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 2: phosphorus trichloride / dichloromethane / 3 h / Reflux 3: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 4: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

C31H28N6O5S2 (68474-81-7) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 2.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 3.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 3.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 3 steps 1: phosphorus trichloride / dichloromethane / 3 h / Reflux 2: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 3: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + Glyoxilic acid (298-12-4) → C26H24N6O6S2

Conditions	Yield
Stage #1: Glyoxilic acid With 1,1'-carbonyldiimidazole In dichloromethane Stage #2: diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate In dichloromethane at 40℃; for 10h; Reagent/catalyst;	98.8%

2,2-dimercaptoacetic acid + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → C26H26N6O5S4

Conditions	Yield
With 1,1'-carbonyldiimidazole In ethyl acetate at 40℃; for 10h;	98.6%

chlorocarbonyl-[4-(4-methoxy-benzyloxy)-phenyl]-acetic acid 4-methoxy-benzyl ester (64952-86-9) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R,7S)-7-Methoxy-7-{2-(4-methoxy-benzyloxycarbonyl)-2-[4-(4-methoxy-benzyloxy)-phenyl]-acetylamino}-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (66216-32-8)

Conditions	Yield
With pyridine	75%

2-[(3S)-(4-ethyl-2,3-dioxo-1-piperazinyl)carboxamido]-3-formyloxybutyryl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R,7S)-7-[[(3S)-2-[(4-ethyl-2,3-dioxo-1-piperazinyl)carboxamido]-3-formyloxy-1-oxobutyl]amino]-7-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester

Conditions	Yield
With triethylamine In dichloromethane at -10℃;	51.5%

gloutaric dichloride (2873-74-7) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → C29H30N6O7S2

Conditions	Yield
With pyridine In dichloromethane Cooling with ice;	17%

L-α-[[[(4-methoxyphenyl)-methoxy]carbonyl]amino]-2-thiopheneacetic acid (59966-06-2) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[(Ξ)-2-(4-methoxy-benzyloxycarbonylamino)-2-thiophen-2-yl-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (64044-40-2)

Conditions	Yield
(i) diisopropylethylamine, isobutyl chloroformate, CH2Cl2, (ii) /BRN= 5406406/; Multistep reaction;

cyanomethylmercapto acetyl chloride (52069-55-3) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → Cefmetazole (56796-20-4, 82263-66-9)

Conditions	Yield
(i) PhNEt2, 1,2-dichloroethane, (ii) CF3CO2H, anisole; Multistep reaction;

(1-methyl-4-nitro-1H-imidazol-2-ylsulfanyl)-acetyl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(1-methyl-4-nitro-1H-imidazol-2-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-33-0)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(3-methyl-5-nitro-3H-imidazol-4-ylsulfanyl)-acetyl chloride (72193-39-6) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(3-methyl-5-nitro-3H-imidazol-4-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-31-8)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(1-methyl-5-nitro-1H-imidazol-2-ylsulfanyl)-acetyl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(1-methyl-5-nitro-1H-imidazol-2-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-34-1)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(1-methyl-5-nitro-1H-imidazol-4-ylsulfanyl)-acetyl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(1-methyl-5-nitro-1H-imidazol-4-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-32-9)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(R)-2-amino-4-thiophen-2-yl-4H-oxazol-5-one; hydrochloride (67645-41-4) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((R)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (67780-07-8)

Conditions	Yield
With methyloxirane In dichloromethane; N,N-dimethyl-formamide

(S)-2-amino-4-thiophen-2-yl-4H-oxazol-5-one; hydrochloride (67645-39-0) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (65642-60-6)

Conditions	Yield
With methyloxirane In dichloromethane; N,N-dimethyl-formamide

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + Carbonic acid benzyl ester 4-chlorocarbonylmethyl-phenyl ester (86862-84-2) → (6R,7S)-7-[2-(4-Benzyloxycarbonyloxy-phenyl)-acetylamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (86862-87-5)

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 0.5h; Yield given;

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R,7R)-7-[2-Carboxy-2-(4-hydroxy-phenyl)-acetylamino]-6-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / pyridine 2: 100 percent / AlCl3, anisole / 0.5 h / 0 °C View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7t-((Ξ)-2-amino-2-thiophen-3-yl-acetylamino)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) diisopropylethylamine, isobutyl chloroformate, CH2Cl2, (ii) /BRN= 5406406/ 2: CF3CO2H, anisole View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (65700-47-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: propyleneoxide / CH2Cl2; dimethylformamide 2: CF3CO2H, anisole / CH2Cl2 View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((R)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (74378-97-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: propyleneoxide / CH2Cl2; dimethylformamide 2: CF3CO2H, anisole / CH2Cl2 View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 2-Bromoacetyl bromide (598-21-0) → 7-bromoacetamide-7-methoxy-3-(1-methyl-1H-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid diphenyl methyl ester (70035-75-5)

Conditions	Yield
Stage #1: diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate; 2-Bromoacetyl bromide With pyridine In dichloromethane at -30 - -20℃; for 1h; Stage #2: With N-Bromosuccinimide In methanol; dichloromethane at 0 - 5℃; for 1h;
With N,N-dimethyl-aniline In ethyl acetate at -5 - 0℃;

methanol (67-56-1) + (6R-cis)-7-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-7-(methylthio)-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester (67366-04-5) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 2-Bromoacetyl bromide (598-21-0) → 7-bromoacetamide-7-methoxy-3-(1-methyl-1H-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid diphenyl methyl ester (70035-75-5)

Conditions

Yield

Stage #1: (6R-cis)-7-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-7-(methylthio)-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester; diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate; 2-Bromoacetyl bromide With pyridine In dichloromethane at -30 - -20℃; for 1h; Stage #2: In dichloromethane; water at 0 - 5℃; Stage #3: methanol With N-Bromosuccinimide; sodium thiosulfate Purification / work up; more than 3 stages;

Upstream product

• 137-07-5 2-amino-benzenethiol 
• 75072-10-5 (6R,7S)-7-[1-Chloro-but-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 53090-86-1 7β-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>ceph-3-em-4-oic acid benzhydryl ester 
• 47653-82-7 (6R,7R)-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-aza-bicyclo [4.2.0]oct-2-ene-2-carboxylic acid 
• 24209-38-9 (6R,7R)-7-amino-3-[(1H-1-methyltetrazol-5-yl)thio]methylceph-3-em-4-carboxylic acid 
• 957-68-6 7-Aminocephalosporanic acid 
• 75072-09-2 (6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 57793-21-2 (6R,7S)-7-(5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-pentanoylamino)-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 56023-19-9 (6R)-7t-(3,5-di-tert-butyl-4-hydroxy-benzylideneamino)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 83934-73-0 (R)-3-(1-Methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7-[2,2,3-trichloro-3-phenyl-prop-(E)-ylideneamino]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 53090-86-1 (R)-7-Amino-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 83934-79-6 (S)-7-[(Z)-2-Chloro-3-phenyl-prop-2-en-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 64278-77-9 (6R-cis)-7-methoxy-3-<<(1-methyl-1-H-tetrazol-5-yl)thio>methyl>-8-oxo<(phenylacetyl)amino>-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester 
• 68474-81-7 C₃₁H₂₈N₆O₅S₂ 

Downstream Products

• 74356-00-6 cefotetan disodium 
• 69712-56-7 cefotetan 
• 70035-75-5 7-bromoacetamide-7-methoxy-3-(1-methyl-1H-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid diphenyl methyl ester 
• 65700-47-2 (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 77119-51-8 7β-<(R)-2-<3-(3,4-diacetoxybenzoyl)-3-methylureido>-2-phenylacetamido>-7α-methoxy-3-<(1-methyl-1H-tetrazol-5-yl)thiomethyl>-3-cephem-4-carboxylic acid 
• 77127-99-2 7β-<(R)-2-<3-(3,4-dihydroxybenzoyl)-3-methylureido>-2-phenylacetamido>-7α-methoxy-3-<(1-methyl-1H-tetrazol-5-yl)thiomethyl>-3-cephem-4-carboxylic acid 
• 86862-87-5 (6R,7S)-7-[2-(4-Benzyloxycarbonyloxy-phenyl)-acetylamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 66216-32-8 (6R,7S)-7-Methoxy-7-{2-(4-methoxy-benzyloxycarbonyl)-2-[4-(4-methoxy-benzyloxy)-phenyl]-acetylamino}-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 65642-60-6 (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 67780-07-8 (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((R)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 56796-20-4 Cefmetazole 
• 61807-78-1 7β-bromoacetamido-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-Δ³-cephem-4-carboxylic acid 

Relevant articles and documents

7 β-amino -7 α-methoxy-3-cephem compound preparation method

The invention relates to a preparation method of a medical raw material 7beta-amino-7lapha-methoxy-3-cephem compound. Methods in prior arts have the problems of more steps and low yield. According to the 7beta-amino-7lapha-methoxy-3-cephem compound preparation method provided by the invention, a beta-lactam compound is adopted as a raw material, and is subjected to a reaction with bis(trichloromethyl)carbonate under the existence of an organic alkali, such that a iminochloride-beta-lactam compound is produced; methanol is added for alcoholysis, such that the 7beta-amino-7lapha-methoxy-3-cephem compound is produced. The method provided by the invention has the advantages of mild and easy-to-control reaction conditions, high yield, no product of 7alpha-methoxy-7beta-amino-3-cephem compound isomer, and easy separation. With the method, the 7beta-amino-7lapha-methoxy-3-cephem compound product with ultrahigh purity can be obtained.

A novel synthetic route to 7-MAC from 7-ACA

An efficient and practical seven-step procedure is described for the synthesis of (6R,7S)-benzhydryl-7-amino-7-methoxy-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-5-thia-1-aza-bicyclo [4.2.0]oct-2-ene-2-carboxylate (7-MAC, 3) with overall yield of 49?%. This synthesis features a convenient and highly selective method for the introduction of 7α-methoxy group to cephalosporin nucleus in 10 using MeOLi/t-BuOCl in THF.

Deacylation of Amides: Removal of the Acyl Side-chain from Cephamycin Derivatives

Diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-methyl>-Δ3-cephem-4-carboxylate (9) is obtained from a cephamycin C derivative by treatment of an imino chloride intermediate with o-aminobenzenethiol.