146464-90-6

Usage

Uses

Used in Research Applications:
α-Propargylhomoterephthalic acid dimethyl ester is used as a research chemical for the study of organic syntheses, chemical reactions, and the formation of polymers. Its unique structure and reactivity make it a valuable compound for exploring new chemical pathways and developing novel materials.
Used in Chemical Synthesis Industry:
α-Propargylhomoterephthalic acid dimethyl ester is used as a key intermediate in the synthesis of complex organic molecules and polymers. Its versatility in click chemistry allows for the efficient construction of molecular structures with potential applications in various fields, such as pharmaceuticals, materials science, and nanotechnology.
Used in Materials Science:
α-Propargylhomoterephthalic acid dimethyl ester is used as a building block in the development of new materials with unique properties, such as high thermal stability, electrical conductivity, or mechanical strength. Its incorporation into polymer matrices can lead to the creation of advanced materials for use in aerospace, electronics, or other high-performance applications.

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

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

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 academic research and scientific papers

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.

A suitable industrial production pula Qu Sha method for the preparation of

The invention relates to the field of pharmaceutical chemistry technology, and more specifically relates to an anticarcinogen 10-Propargyl-10-deazaaminopterin (Pralatrexate) and synthesis of an intermediate thereof. The invention has the advantages of simple operation, low contents of related impurities, easiness in purification of intermediate, thereby avoiding purification mode of column chromatography, and the invention can be applied to large scale production of Pralatrexate bulk drug as well as preparation and purification method of important 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.

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 PREPARATION OF AN ANTIFOLATE AGENT

The specification relates to a process for preparation of an antifolate compound of formula 7, such as Pralatrexate. Also, disclosed are intermediates and processes for preparation of intermediates useful in the preparation of the antifolate compound. The substituents Y, Z, R, R1 and R2 are as described herein. The processes and intermediates can provide an alternate route to the synthesis of the antifolate compound. Further, the processes can help to avoid distillation or evaporation of high boiling point solvents, chromatographic purification and use of hazardous combination of solvents; and can also provide a product having high purity, all of which are desirable for synthesis on a large scale.

Optically Pure Diastereomers of 10-Propargyl-10-Deazaaminopterin and Methods of Using Same

The present invention relates to diastereomers of 10-propargyl-10-deazaminopterin, compositions comprising optically pure diastereomers of 10-propargyl-10-deazaminopterin, in particular the two (R,S) diastereomers about the C10 position. Methods of preparation of these diastereomers, compositions containing them, and their use for the treatment of conditions related to inflammatory disorders and cancer are also disclosed.

Treatment of T-cell lymphoma using 10-propargyl-10-deazaaminopterin

T cell lymphoma is treated by administering to a patient suffering from T cell lymphoma a therapeutically effective amount of 10-propargyl-10-deazaaminopterin. Remission is observed in human patients, even with drug resistant T cell lymphoma at weekly dosages levels as low as 30 mg/m2. In general, the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m2 per dose.

Antiinflammatory and antineoplastic 5-deazaaminopterins and 5,10-dideazaaminopterins

Antiinflammatory and antineoplastic 5-deazaaminopterins and 5,10-dideazaaminopterins and their 5 and 10 alkyl analogs. A method for the treatment and prevention of inflammatory disease, such as rheumatoid arthritis, and for suppression and prevention of neoplastic growth in tumors and in blood forming tissues. A process for preparation of 10-deazaaminopterins.

Heteroaroyl 10-deazaamino-pterine compounds and use for rheumatoid arthritis

There is disclosed certain heteroaroyl 10-deazaaminopterin and 5, 10 and 8, 10 di deazaminopterin compounds and their use for treatment of rheumatoid arthritis and related diseases and preparative process. Also disclosed are 10 alkenyl-(and alkynyl) 10-deazaminopterins also disclosed for treatment of rheumatoid arthritis and for leukemia and ascites tumors and preparative process.