152305-23-2

Usage

Uses

Used in Pharmaceutical Industry:
(S)-4-(4-Aminobenzyl)-2(1H)-oxazolidinone is used as an intermediate for the synthesis of zolmitriptan (sc-220415), which is a novel inhibitor of the cytochrome P-450 enzyme aromatase. This application is significant because it helps in the development of new treatments for various medical conditions.
Used in Aromatase Inhibition:
(S)-4-(4-Aminobenzyl)-2(1H)-oxazolidinone is used as an intermediate in the creation of zolmitriptan, a compound that acts as a novel inhibitor of the cytochrome P-450 enzyme aromatase. This inhibition is crucial in the treatment of certain hormonally driven conditions, such as breast cancer, by reducing the production of estrogen in the body.
Used in Drug Synthesis:
(S)-4-(4-Aminobenzyl)-2(1H)-oxazolidinone is utilized as a key intermediate in the synthesis of various pharmaceutical compounds. Its unique chemical properties make it an essential building block in the development of new drugs, contributing to the advancement of medical treatments and therapies.

InChI:InChI=1/C10H12N2O2/c11-8-3-1-7(2-4-8)5-9-6-14-10(13)12-9/h1-4,9H,5-6,11H2,(H,12,13)

Synthetic route

(S)-4-(4'-nitrobenzyl)-1,3-oxazolidin-2-one (139264-55-4) → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal In ethanol under 760 Torr; Ambient temperature;	79%
With indium; ammonium chloride In ethanol for 4h; Heating;	47%
With hydrogen; nickel In methanol at 30℃; for 6 - 7h;

(S)-2-amino-3-(4-aminophenyl)propan-1-ol (726134-79-8) + Diethyl carbonate (105-58-8) → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
potassium carbonate at 115 - 135℃; for 2.5h;	75%

(S)-4-Benzyl-2-oxazolidinone (90719-32-7) + MeX → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / fuming HNO3 / CH2Cl2 / 2 h / 20 °C 2: 47 percent / NH4Cl; In / ethanol / 4 h / Heating View Scheme

L-phenylalanine (63-91-2) + PhMgHal → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: 53 percent / conc. H2SO4, conc. HNO3 / 0.5 h / Ambient temperature 2: 76 percent / SOCl2 / 4 h / -10 - 40 °C 3: 65 percent / NaBH4 / ethanol; H2O / 4 h / Heating 4: 75 percent / 0.2M aq. KOH / toluene / 2 h / 0 - 20 °C 5: 79 percent / H2, aq. HCl / 10percent Pd/C / ethanol / 760 Torr / Ambient temperature View Scheme

4-nitro-3-phenyl-L-alanine (949-99-5) → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 76 percent / SOCl2 / 4 h / -10 - 40 °C 2: 65 percent / NaBH4 / ethanol; H2O / 4 h / Heating 3: 75 percent / 0.2M aq. KOH / toluene / 2 h / 0 - 20 °C 4: 79 percent / H2, aq. HCl / 10percent Pd/C / ethanol / 760 Torr / Ambient temperature View Scheme

(S)-(-)-2-amino-3-(4-nitrophenyl)propan-1-ol (89288-22-2) → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / 0.2M aq. KOH / toluene / 2 h / 0 - 20 °C 2: 79 percent / H2, aq. HCl / 10percent Pd/C / ethanol / 760 Torr / Ambient temperature View Scheme

(S)-4-nitrophenylalanine methyl ester hydrochloride (17193-40-7) → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / NaBH4 / ethanol; H2O / 4 h / Heating 2: 75 percent / 0.2M aq. KOH / toluene / 2 h / 0 - 20 °C 3: 79 percent / H2, aq. HCl / 10percent Pd/C / ethanol / 760 Torr / Ambient temperature View Scheme

(S)-N-butoxycarbonyl-4-aminophenylalaninol (188404-34-4) → (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2)

Conditions	Yield
With sodium methylate In methanol; butan-1-ol at 5 - 85℃; for 8.5h;

4-iodophenyl isothiocyanate (2059-76-9) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-1-(4-iodophenyl)-3-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-thiourea

Conditions	Yield
With triethylamine In acetone Reflux;	90%

1-isothiocyanato-4-methylbenzene (622-59-3) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-1-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-3-p-tolylthiourea

Conditions	Yield
With triethylamine In acetone Reflux;	88%

p-nitrophenyl isothiocyanate (2131-61-5) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-1-(4-nitrophenyl)-3-(4-((2-oxooxazolidin-4-yl)methyl)-phenyl)thiourea

Conditions	Yield
With triethylamine In acetone Reflux;	82%

(S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) + 4-Bromophenyl isothiocyanate (1985-12-2) → (S)-1-(4-bromophenyl)-3-(4-((2-oxooxazolidin-4-yl)methyl)-phenyl)thiourea

Conditions	Yield
With triethylamine In acetone Reflux;	80%

(S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) + 4-bromobenzenesulfonyl chloride (98-58-8) → (S)-4-bromo-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	79%

ethyl 2-acetyl-5-(1,3-dioxo-1,3-dihydro-2-isoindolyl)pentanoate (55747-45-0) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → ethyl (S)-3-[2-(1,3-dioxoisoindolin-2-yl)ethyl]-5-[(2-oxooxazolidin-4-yl)methyl]-1H-indole-2-carboxylate (868622-21-3)

Conditions	Yield
Stage #1: (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one With hydrogenchloride; sodium nitrite In methanol; water at -5 - 0℃; Industrial scale; Stage #2: ethyl 2-acetyl-5-(1,3-dioxo-1,3-dihydro-2-isoindolyl)pentanoate With sodium acetate In methanol; water at 0 - 30℃; Industrial scale; Stage #3: With hydrogenchloride In methanol for 6h; Fischer Indole Synthesis; Reflux; Industrial scale;	78%

benzaldehyde (100-52-7) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-((E)-4-(benzylideneamino)benzyl)oxazolidin-2-one

Conditions	Yield
In methanol at 20℃; for 0.0833333h;	77.5%

p-toluenesulfonyl chloride (98-59-9) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-methyl-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	76%

4-chloro-benzoyl chloride (122-01-0) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-chloro-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	75%

benzenesulfonyl chloride (98-09-9) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	72%

4-nitro-benzoyl chloride (122-04-3) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-nitro-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	58%

4-methoxy-phenyl-sulphonyl chloride (98-68-0) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-methoxy-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	57%

4-methoxy-benzoyl chloride (100-07-2) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-methoxy-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	54%

4-Fluorobenzenesulfonyl chloride (349-88-2) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-fluoro-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	53%

4-fluorobenzoyl chloride (403-43-0) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-fluoro-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	50%

4-chlorobenzoyl chloride (586-75-4) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-bromo-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	48%

benzoyl chloride (98-88-4) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	47%

(S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-(3-iodo-4-aminobenzyl)-1,3-oxazolidin-2-one (179534-87-3)

Conditions	Yield
With Iodine monochloride; calcium carbonate In methanol; ethyl acetate	45%
With Iodine monochloride; calcium carbonate In methanol for 16h; Ambient temperature;

4-fluorophenyl isothiocyanate (1544-68-9) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-1-(4-fluorophenyl)-3-(4-((2-oxooxazolidin-4-yl)methyl)-phenyl)thiourea

Conditions	Yield
With triethylamine In acetone Reflux;	42%

phenyl isothiocyanate (103-72-0) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-1-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-3-phenylthiourea

Conditions	Yield
With triethylamine In acetone Reflux;	33%

4-chlorobenzenesulfonyl chloride (98-60-2) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-chloro-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	31%

(S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) + 4-Nitrobenzenesulfonyl chloride (98-74-8) → (S)-4-nitro-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	28%

4-Methoxyphenyl isothiocyanate (2284-20-0) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-1-(4-methoxyphenyl)-3-(4-((2-oxooxazolidin-4-yl)methyl)-phenyl)thiourea

Conditions	Yield
With triethylamine In acetone Reflux;	27%

4-methyl-benzoyl chloride (874-60-2) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-4-methyl-N-(4-((2-oxooxazolidin-4-yl)methyl)phenyl)-benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	24%

4-Chlorophenyl isothiocyanate (2131-55-7) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-1-(4-chlorophenyl)-3-(4-((2-oxooxazolidin-4-yl)methyl)-phenyl)thiourea

Conditions	Yield
With triethylamine In acetone Reflux;	19%

(S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → 4-((S)-2-Oxo-oxazolidin-4-ylmethyl)-benzenediazonium; chloride

Conditions	Yield
With hydrogenchloride; sodium nitrite at 0℃; for 0.5h;
With hydrogenchloride; sodium nitrite In water at -10 - 30℃; for 3h;
With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 0.5h;

(S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → (S)-2-<5-(2-oxo-1,3-oxazolidin-4-ylmethyl)-1H-indol-3-yl>ethyl alcohol (179636-99-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: ICl, CaCO3 / methanol / 16 h / Ambient temperature 2: Na2CO3, MgSO4, Pd(OAc)2 / dimethylformamide / 16 h / 110 °C 3: 5 N HCl / methanol / 19 h / Ambient temperature View Scheme

Upstream product

• 949-99-5 4-nitro-3-phenyl-L-alanine 
• 89288-22-2 (S)-(-)-2-amino-3-(4-nitrophenyl)propan-1-ol 
• 188404-34-4 (S)-N-butoxycarbonyl-4-aminophenylalaninol 
• 726134-79-8 (S)-2-amino-3-(4-aminophenyl)propan-1-ol 
• 105-58-8 Diethyl carbonate 
• 17193-40-7 (S)-4-nitrophenylalanine methyl ester hydrochloride 
• 63-91-2 L-phenylalanine 
• 90719-32-7 (S)-4-Benzyl-2-oxazolidinone 
• 139264-55-4 (S)-4-(4'-nitrobenzyl)-1,3-oxazolidin-2-one 

Downstream Products

• 187975-62-8 (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one 

Relevant academic research and scientific papers

AN IMPROVED PROCESS FOR THE PREPARATION OF ZOLMITRIPTAN

Disclosed herein the process for producing pure" Zolmitriptan employing improved reaction conditions which excluded the use of column chromatography.

A NOVEL AND AN IMPROVED PROCESS FOR THE PREPARATION OF (S)-4-(4-AMINOBENZYL)-2- OXAZOLIDINONE

The invention disclosed in this application relates to an improved process for the preparation of the oxazolidinone of formula (I) It comprises (i) Preparing the 4-nitro-(S)-phenylalaninol of formula (IV) by conventional methods. (ii) Reducing the nitro compound of formula (IV), (iii) Reacting the resulting novel compound of the formula (II) with dialkyl carbonate at a temperature in the range of 80-200 °C. to produce the compound of the formula I. The compound of the formula I is useful for the preparation of zolmitriptan which is an important drug for the treatment of migraine.

A process for the purification of (S)-4-((3-(dimethylamino)ethyl)-1H-indol-5yl)-methyl)-2-oxazolidinone

A process for the purification of (S)-4-{[3-(dimethylamino)ethyl]-1H-indol-5yl]-methyl}-2-oxazolidinone and non-solvated, pure (S)-4-{[3-(dimethylamino) ethyl]-1H-indol-5y1]-methyl}-2-oxazolidinone.

Design, synthesis, and evaluation of 4-(4′-aminobenzyl)-2-oxazolidinones as novel inhibitors of the cytochrome P-450 enzyme aromatase

The synthesis of a series of N-alkylated 4-(4′aminobenzyl)-2-oxazolidinones is described using a synthetically useful scheme which avoids the use of phosgene - since the derivatization is undertaken with the oxazolidin-2-one ring intact. The compounds were tested for human placental aromatase (AR) inhibition in vitro, using [1β, 2β-3H]androstenedione as substrate for the AR enzyme. The compounds were found, in general, to be more potent than the standard compound, amino-glutethimide (AG), and as such proved to be good lead compounds in the search for more specific AR inhibitors.

One pot synthesis of 2-oxazolidinone derivatives

The invention provides an improved process for preparing compounds of formula (I)

A novel series of 2,5-substituted tryptamine derivatives as vascular 5HT(1B/1D) receptor antagonists

The design, synthesis, and activity of a novel series of 2,5- substituted tryptamine derivatives at vascular 5HT(1B)-like receptors is described. Several important auxiliary binding sites of the 5HT(1B)-like receptor have been proposed following various modifications to the 2- substituent and especially to the methylene- or ethylene-linked 5-side chain. Careful design of new molecules based on a proposed pharmacophoric model of the 5HT(1B)-like receptor has resulted in the discovery of ethyl 3-[2- (dimethylamino)ethyl]-5-[2-(2,5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2- carboxylate (40), a highly potent, silent, competitive, and selective antagonist which shows affinity at the vascular 5HT(1B)-like receptors only. Changes to the size of the 2-ester substituent have a significant effect on affinity at the 5HT(1B)-like receptor and other receptors. Prudent placement of the carbonyl substituent in the heterocycle of the 5-side chain is crucial for good affinity and selectivity over the 5HT(2A) and other receptors. Several key structural and electronic features were identified which are crucial for producing antagonism within a tryptamine-based series. An electron deficient indole ring system appears essential in order to achieve antagonism, and this is achieved by the inclusion of electron-withdrawing groups at the 2-position of the indole ring. The molecule displacement within the receptor resulting from the inclusion of the bulky 2-substituents also enhances antagonism as this results in the removal of the Π electon density of the indole ring from the region of the receptor normally occupied by the indole ring of 5HT. There also appears to be a structural requirement on the side chain incorporating the protonatable nitrogen, and this is achieved by the inclusion of the bulky 2-ester group which neighbors the 3-ethylamine side chain.