146464-90-6

Basic information

• Product Name: α-propargylhomoterephthalic acid dimethyl ester
• Synonyms: α-propargylhomoterephthalic acid dimethyl ester;Benzeneacetic acid, 4-(methoxycarbonyl)-.alpha.-2-propyn-1-yl-, methyl ester;Methyl 4-(1-Methoxy-1-oxopent-4-yn-2-yl) benzoate;Benzeneacetic acid, 4-(Methoxycarbonyl)-α-2-propyn-1-yl-, Methyl ester;4-(Methoxycarbonyl)-alpha-2-propynyl-benzeneacetic acid methyl ester;Methyl 4-(1-methoxy-1-oxo-4-pentyn-2-yl)benzoate
• CAS NO: 146464-90-6
• Molecular Formula: C₁₄H₁₄O₄
• Molecular Weight: 246.25856
• Mol File: 146464-90-6.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 348.2±32.0 °C(Predicted)
• Appearance: /
• Density: 1.149±0.06 g/cm3(Predicted)
• CAS DataBase Reference: α-propargylhomoterephthalic acid dimethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: α-propargylhomoterephthalic acid dimethyl ester(146464-90-6)
• EPA Substance Registry System: α-propargylhomoterephthalic acid dimethyl ester(146464-90-6)

Safety Data

• Hazardous Substances Data: 146464-90-6(Hazardous Substances Data)

Usage

General Description

α-Propargylhomoterephthalic acid dimethyl ester is a specialized chemical compound that features a unique structure involving the esterification of alpha propargyl homoterephthalic acid, an organic chemical which consists of a propargyl group, commonly used in click chemistry. α-propargylhomoterephthalic acid dimethyl ester is not widely studied, hence specific properties like color, appearance, melting point, boiling point, and other chemical properties are often not documented clearly. However, the presence of dimethyl ester indicates that it is likely to be a soluble, liquid compound whose reactivity and other properties could derive from this functional group. As a highly specialized compound, it is primarily synthesized and used for research purposes, especially those involving the study of organic syntheses, chemical reactions, formation of polymers and much more.

Synthetic route

methyl 4-(2-methoxy-2-oxoethyl)benzoate (52787-14-1) + propargyl bromide (106-96-7) → α-propargylhomoterephthalic acid dimethyl ester (146464-90-6)

Conditions	Yield
Stage #1: methyl 4-(2-methoxy-2-oxoethyl)benzoate; propargyl bromide In tetrahydrofuran at -10℃; Inert atmosphere; Stage #2: With lithium hexamethyldisilazane In tetrahydrofuran at -10℃; Temperature; Solvent; Reagent/catalyst;	87%
Stage #1: methyl 4-(2-methoxy-2-oxoethyl)benzoate With sodium hydride In tetrahydrofuran at 0 - 15℃; Autoclave; Stage #2: propargyl bromide In tetrahydrofuran at -20 - 10℃; for 5h;	64.5%
With potassium hydride 1.) THF, 0 deg C, 1 h, 2.) THF, a0) o deg C, 30 min, b) RT, 16 h; Yield given. Multistep reaction;

methyl 4-(2-methoxy-2-oxoethyl)benzoate (52787-14-1) + propargyl bromide (106-96-7) → dipropargyl homoterephthalic acid dimethyl ester (1026380-17-5) + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl acetamide at 25 - 30℃; for 26h; Concentration;	A n/a B 65.6%
Stage #1: methyl 4-(2-methoxy-2-oxoethyl)benzoate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Stage #2: propargyl bromide In tetrahydrofuran; mineral oil at 0 - 20℃; for 17h;
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl acetamide at 25 - 30℃; Concentration;

propargyl bromide (106-96-7) → dipropargyl homoterephthalic acid dimethyl ester (1026380-17-5) + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6)

Conditions	Yield
Stage #1: methyl 4-(2-methoxy-2-oxoethyl)benzoate With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: propargyl bromide In tetrahydrofuran at 0 - 20℃; for 17h; Stage #3: With acetic acid In tetrahydrofuran

4-(carboxymethyl)benzoic acid (501-89-3) → α-propargylhomoterephthalic acid dimethyl ester (146464-90-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / 24 h / Reflux; Autoclave 2.1: sodium hydride / tetrahydrofuran / 0 - 15 °C / Autoclave 2.2: 5 h / -20 - 10 °C View Scheme

C8H9BrN6*BrH + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → methyl-4-(2-((2,4-diaminopteridin-6-yl)methyl)-1-methoxy-1-oxopent-4-yn-2-yl)benzoate (146464-91-7)

Conditions	Yield
Stage #1: α-propargylhomoterephthalic acid dimethyl ester With sodium hydride In N,N-dimethyl-formamide at -5 - 0℃; for 1.5h; Stage #2: C8H9BrN6*BrH In N,N-dimethyl-formamide at -25 - 20℃; for 5h;	85%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 10-propargyl-10-carbomethoxy-4-deoxy-4-amino-10-deazapteroic acid methyl ester hydrobromide salt (1548618-47-8)

Conditions	Yield
Stage #1: 6-bromomethyl-2,4-diaminopteridine hydrobromide; α-propargylhomoterephthalic acid dimethyl ester With sodium hydride In N,N-dimethyl acetamide at -20 - -10℃; Stage #2: With hydrogen bromide In methanol; dichloromethane; water; isopropyl alcohol at 0 - 5℃; Concentration;	73.7%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → methyl-4-(2-((2,4-diaminopteridin-6-yl)methyl)-1-methoxy-1-oxopent-4-yn-2-yl)benzoate (146464-91-7)

Conditions	Yield
With potassium hydride 1.) DMF, 0 deg C, 30 min, 2.) DMF, 2-propanol, 10 deg C, 2,5 h; Multistep reaction;
Stage #1: α-propargylhomoterephthalic acid dimethyl ester With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 5℃; Stage #2: 6-bromomethyl-2,4-diaminopteridine hydrobromide In N,N-dimethyl-formamide; mineral oil at -25 - 20℃; for 6h;
With sodium hydride In N,N-dimethyl acetamide at -20 - -10℃; Concentration;

2,4-diamino-5-methyl-6-(bromomethyl)pyrido<2,3-d>pyrimidine (101348-32-7) + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 4-[1-(2,4-Diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-ylmethyl)-1-methoxycarbonyl-but-3-ynyl]-benzoic acid methyl ester (184918-77-2)

Conditions	Yield
With sodium hydride 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, from -25 deg C to 25 deg C; Yield given. Multistep reaction;

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 4-[1-(2,4-Diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-ylmethyl)-but-3-ynyl]-benzoic acid (184918-81-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, from -25 deg C to 25 deg C 2: 74 percent / 4N NaOH / dimethylsulfoxide / 96 h / 20 - 60 °C 3: 89 percent / dimethylsulfoxide / 0.83 h / 105 - 110 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 4-[1-Carboxy-1-(2,4-diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-ylmethyl)-but-3-ynyl]-benzoic acid (184918-79-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, from -25 deg C to 25 deg C 2: 74 percent / 4N NaOH / dimethylsulfoxide / 96 h / 20 - 60 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → C25H27N5O4

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, from -25 deg C to 25 deg C 2: 74 percent / 4N NaOH / dimethylsulfoxide / 96 h / 20 - 60 °C 3: 89 percent / dimethylsulfoxide / 0.83 h / 105 - 110 °C 4: Et3N / dimethylformamide / 0.25 h / 20 - 25 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → (S)-2-{4-[1-(2,4-Diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-ylmethyl)-but-3-ynyl]-benzoylamino}-pentanedioic acid diethyl ester

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, from -25 deg C to 25 deg C 2: 74 percent / 4N NaOH / dimethylsulfoxide / 96 h / 20 - 60 °C 3: 89 percent / dimethylsulfoxide / 0.83 h / 105 - 110 °C 4: Et3N / dimethylformamide / 0.25 h / 20 - 25 °C 5: dimethylformamide / 0.5 h View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 4-(1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl)benzoic acid (146464-93-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) KH / 1.) DMF, 0 deg C, 30 min, 2.) DMF, 2-propanol, 10 deg C, 2,5 h 2: 10percent aq. NaOH / 2-methoxy-ethanol; H2O / 4 h / Ambient temperature 3: dimethylsulfoxide / 0.08 h / 120 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0 - 5 °C 1.2: 6 h / -25 - 20 °C 2.1: sodium hydroxide; water / 2-methoxy-ethanol / 4 h / 20 °C 3.1: dimethyl sulfoxide / 0.17 h / 115 - 120 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.75 h / -5 - 0 °C 1.2: 2.5 h / -25 - -20 °C 2.1: water; sodium hydroxide / 2-methoxy-ethanol / 4 h / 15 - 20 °C 3.1: dimethyl sulfoxide / 0.75 h / 120 - 125 °C 3.2: 24 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 2: hydrogen bromide / methanol; isopropyl alcohol; dichloromethane; water / 0 - 5 °C 3: potassium hydroxide / water; 2-methoxy-ethanol / 6 h / 25 - 30 °C 4: dimethyl sulfoxide / 110 - 115 °C View Scheme
Multi-step reaction with 5 steps 1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 2: hydrogen bromide / methanol; isopropyl alcohol; dichloromethane; water / 0 - 5 °C 3: potassium hydroxide / water; 2-methoxy-ethanol / 6 h / 25 - 30 °C 4: methanol / 0 - 5 °C 5: N,N-dimethyl acetamide / 1 h / 50 - 110 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 4-(2-carboxy-1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl)benzoic acid (146464-92-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) KH / 1.) DMF, 0 deg C, 30 min, 2.) DMF, 2-propanol, 10 deg C, 2,5 h 2: 10percent aq. NaOH / 2-methoxy-ethanol; H2O / 4 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0 - 5 °C 1.2: 6 h / -25 - 20 °C 2.1: sodium hydroxide; water / 2-methoxy-ethanol / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 1.2: 0 - 5 °C 2.1: potassium hydroxide / water / 4 h / 20 - 25 °C 2.2: 15 h / 20 - 25 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → C23H24N6O4 (948552-65-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) KH / 1.) DMF, 0 deg C, 30 min, 2.) DMF, 2-propanol, 10 deg C, 2,5 h 2: 10percent aq. NaOH / 2-methoxy-ethanol; H2O / 4 h / Ambient temperature 3: dimethylsulfoxide / 0.08 h / 120 °C 4: Et3N / dimethylformamide / 1 h / Ambient temperature View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → pralatrexate

Conditions	Yield
Multi-step reaction with 6 steps 1: 1.) KH / 1.) DMF, 0 deg C, 30 min, 2.) DMF, 2-propanol, 10 deg C, 2,5 h 2: 10percent aq. NaOH / 2-methoxy-ethanol; H2O / 4 h / Ambient temperature 3: dimethylsulfoxide / 0.08 h / 120 °C 4: Et3N / dimethylformamide / 1 h / Ambient temperature 5: Et3N / dimethylformamide / 2 h / Ambient temperature 6: 10percent aq. NaOH / 2-methoxy-ethanol; H2O / 2 h / Ambient temperature View Scheme
Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0 - 5 °C 1.2: 6 h / -25 - 20 °C 2.1: sodium hydroxide; water / 2-methoxy-ethanol / 4 h / 20 °C 3.1: dimethyl sulfoxide / 0.17 h / 115 - 120 °C 4.1: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 - 25 °C 5.1: sodium hydroxide; methanol / 8 h / 20 - 25 °C 5.2: 24 h / 20 - 25 °C 5.3: pH 4 View Scheme
Multi-step reaction with 5 steps 1.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; sodium hydride / mineral oil / 0.5 h / -10 - 0 °C 1.2: -5 - 20 °C 2.1: sodium hydroxide; water / isopropyl alcohol / 20 °C 2.2: pH 7.5 3.1: triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 120 - 130 °C 3.2: 0 - 20 °C 4.1: triethylamine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C 5.1: sodium hydroxide; water / methanol / 15 - 20 °C 5.2: pH 7 - 8 View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 10-propargyl-10-deazaaminopterin diethyl ester (146464-94-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.) KH / 1.) DMF, 0 deg C, 30 min, 2.) DMF, 2-propanol, 10 deg C, 2,5 h 2: 10percent aq. NaOH / 2-methoxy-ethanol; H2O / 4 h / Ambient temperature 3: dimethylsulfoxide / 0.08 h / 120 °C 4: Et3N / dimethylformamide / 1 h / Ambient temperature 5: Et3N / dimethylformamide / 2 h / Ambient temperature View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.75 h / -5 - 0 °C 1.2: 2.5 h / -25 - -20 °C 2.1: water; sodium hydroxide / 2-methoxy-ethanol / 4 h / 15 - 20 °C 3.1: dimethyl sulfoxide / 0.75 h / 120 - 125 °C 3.2: 24 h / 20 °C 4.1: triethylamine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / N,N-dimethyl-formamide / 1 h / -5 - 0 °C 4.2: 2 h / -15 - -10 °C View Scheme

2,4-diamino-6-bromomethylpteridine hydrobromide.0.2 isopropanol + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → methyl-4-(2-((2,4-diaminopteridin-6-yl)methyl)-1-methoxy-1-oxopent-4-yn-2-yl)benzoate (146464-91-7)

Conditions	Yield
In N-methyl-acetamide

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 10-propargyl-10-deazaaminopterin dimethyl ester (374777-77-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0 - 5 °C 1.2: 6 h / -25 - 20 °C 2.1: sodium hydroxide; water / 2-methoxy-ethanol / 4 h / 20 °C 3.1: dimethyl sulfoxide / 0.17 h / 115 - 120 °C 4.1: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 - 25 °C View Scheme
Multi-step reaction with 4 steps 1.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; sodium hydride / mineral oil / 0.5 h / -10 - 0 °C 1.2: -5 - 20 °C 2.1: sodium hydroxide; water / isopropyl alcohol / 20 °C 2.2: pH 7.5 3.1: triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 120 - 130 °C 3.2: 0 - 20 °C 4.1: triethylamine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 1.2: 0 - 5 °C 2.1: potassium hydroxide / water / 4 h / 20 - 25 °C 2.2: 15 h / 20 - 25 °C 3.1: dimethyl sulfoxide / 110 - 115 °C 3.2: 50 - 55 °C 4.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl acetamide / 0.5 h / 0 - 5 °C / Inert atmosphere 4.2: 21 h / 0 - 25 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → C25H27N7O5 (1320211-82-2) + C25H27N7O5 (1320211-79-7)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0 - 5 °C 1.2: 6 h / -25 - 20 °C 2.1: sodium hydroxide; water / 2-methoxy-ethanol / 4 h / 20 °C 3.1: dimethyl sulfoxide / 0.17 h / 115 - 120 °C 4.1: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 - 25 °C 5.1: CHIRALPAK AD 20μ, 11 cm id.x.27 cm L / ethanol / 30 °C View Scheme

6-bromomethyl-pteridine-2,4-diamine (59368-16-0) + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → methyl-4-(2-((2,4-diaminopteridin-6-yl)methyl)-1-methoxy-1-oxopent-4-yn-2-yl)benzoate (146464-91-7)

Conditions	Yield
Stage #1: α-propargylhomoterephthalic acid dimethyl ester With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; sodium hydride In mineral oil at -10 - 0℃; for 0.5h; Stage #2: 6-bromomethyl-pteridine-2,4-diamine In mineral oil at -5 - 20℃;	40.2 g
Stage #1: α-propargylhomoterephthalic acid dimethyl ester With sodium hydride In N,N-dimethyl-formamide at -5 - 0℃; for 0.75h; Stage #2: 6-bromomethyl-pteridine-2,4-diamine In N,N-dimethyl-formamide at -25 - -20℃; for 2.5h;

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → C19H16N6O4*ClH

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; sodium hydride / mineral oil / 0.5 h / -10 - 0 °C 1.2: -5 - 20 °C 2.1: sodium hydroxide; water / isopropyl alcohol / 20 °C 2.2: pH 7.5 View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 10-propargyl-10-carboxy-4-deoxy-4-amino-10-deazapteroic acid sodium salt (1445586-50-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; sodium hydride / mineral oil / 0.5 h / -10 - 0 °C 1.2: -5 - 20 °C 2.1: sodium hydroxide; water / isopropyl alcohol / 20 °C 2.2: pH 7.5 3.1: triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 120 - 130 °C 3.2: 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 1.2: 0 - 5 °C 2.1: potassium hydroxide / water / 4 h / 20 - 25 °C 2.2: 15 h / 20 - 25 °C 3.1: dimethyl sulfoxide / 110 - 115 °C 3.2: 50 - 55 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 1.2: 0 - 5 °C 2.1: potassium hydroxide / water / 4 h / 20 - 25 °C 2.2: 15 h / 20 - 25 °C 3.1: methanol / 0 - 5 °C 4.1: N,N-dimethyl acetamide / 1 h / 50 - 110 °C 4.2: 0 - 15 °C View Scheme
Multi-step reaction with 5 steps 1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 2: hydrogen bromide / methanol; isopropyl alcohol; dichloromethane; water / 0 - 5 °C 3: potassium hydroxide / water; 2-methoxy-ethanol / 6 h / 25 - 30 °C 4: dimethyl sulfoxide / 110 - 115 °C 5: sodium hydroxide / water / 0 - 15 °C View Scheme
Multi-step reaction with 6 steps 1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 2: hydrogen bromide / methanol; isopropyl alcohol; dichloromethane; water / 0 - 5 °C 3: potassium hydroxide / water; 2-methoxy-ethanol / 6 h / 25 - 30 °C 4: methanol / 0 - 5 °C 5: N,N-dimethyl acetamide / 1 h / 50 - 110 °C 6: sodium hydroxide / water / 0 - 15 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 10-propargyl-10-carboxy-4-deoxy-4-amino-10-deazapteroic acid bis(dicyclohexylamine) salt

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 1.2: 0 - 5 °C 2.1: potassium hydroxide / water / 4 h / 20 - 25 °C 2.2: 15 h / 20 - 25 °C 3.1: methanol / 0 - 5 °C View Scheme
Multi-step reaction with 4 steps 1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 2: hydrogen bromide / methanol; isopropyl alcohol; dichloromethane; water / 0 - 5 °C 3: potassium hydroxide / water; 2-methoxy-ethanol / 6 h / 25 - 30 °C 4: methanol / 0 - 5 °C View Scheme

α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 10-propargyl-10-carbomethoxy-4-deoxy-4-amino-10-deazapteroic acid methyl ester hydrobromide salt (1548618-47-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl acetamide / -20 - -10 °C 2: hydrogen bromide / methanol; isopropyl alcohol; dichloromethane; water / 0 - 5 °C View Scheme

Upstream product

• 501-89-3 4-(carboxymethyl)benzoic acid 
• 52787-14-1 methyl 4-(2-methoxy-2-oxoethyl)benzoate 
• 106-96-7 propargyl bromide 

Downstream Products

• 374777-77-2 10-propargyl-10-deazaaminopterin dimethyl ester 
• 1320211-82-2 C₂₅H₂₇N₇O₅ 
• 1320211-79-7 C₂₅H₂₇N₇O₅ 
• 146464-91-7 methyl-4-(2-((2,4-diaminopteridin-6-yl)methyl)-1-methoxy-1-oxopent-4-yn-2-yl)benzoate 
• 1548618-47-8 10-propargyl-10-carbomethoxy-4-deoxy-4-amino-10-deazapteroic acid methyl ester hydrobromide salt 
• 1445586-50-4 10-propargyl-10-carboxy-4-deoxy-4-amino-10-deazapteroic acid sodium salt 
• 146464-94-0 10-propargyl-10-deazaaminopterin diethyl ester 
• 146464-95-1 pralatrexate 
• 948552-65-6 C₂₃H₂₄N₆O₄ 
• 146464-92-8 4-(2-carboxy-1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl)benzoic acid 
• 146464-93-9 4-(1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl)benzoic acid 
• 184918-79-4 4-[1-Carboxy-1-(2,4-diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-ylmethyl)-but-3-ynyl]-benzoic acid 
• 184918-81-8 4-[1-(2,4-Diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-ylmethyl)-but-3-ynyl]-benzoic acid 

Relevant articles and documents

Preparation method for pralatrexate intermediate

The invention specifically relates to a preparation method for a pralatrexate intermediate, belonging to the technical field of medicine. According to the preparation method for the intermediate alpha-propargyl-(4-methylformate)-methylphenyl acetate, operation is more convenient and the content of impurities is lower; and in particular, the ratio of dithropropyl impurities in the produced intermediate is obviously reduced, the yield of the target product alpha-propargyl-(4-methylformate)-methylphenyl acetate is significantly increased, and product purity is greatly improved. The preparation method can be applied to large-scale production of pralatrexate bulk drugs and preparation of pralatrexate intermediates.

IMPROVED PROCESS FOR THE PREPARATION OF PRALATREXATE

An improved process for the preparation of Pralatrexate which is less hazardous. The invention further relates to novel intermediates and process thereof useful for the preparation of Pralatrexate. The present invention also relates to a substantially pure Pralatrexate and a process for obtaining the same in high yield.

PROCESS FOR PRALATREXATE

The present invention provides a novel process for the purification of alpha-propargylhomoterephthalic acid dimethyl ester substantially free of homoterephthalic acid dimethyl ester. The present invention also provides a novel process for the purification of pralatrexate.