40391-99-9

Basic information

• Product Name: Pamidronic acid
• Synonyms: PAMIDRONIC ACID;PAMIDRONIC ACID SODIUM SALT;Rescriptor;amidronate;DLV;(3-amino-1-hydroxypropylidene)bisphosphonic acid;(3-Amino-1-hydroxypropylidene)diphosphonic acid;3-AMINO-1-HYDROXY-1,1-PROPANEDIPHOSPHONIC ACID
• CAS NO: 40391-99-9
• Molecular Formula: C₃H₁₁NO₇P₂
• Molecular Weight: 235.07
• EINECS: 254-905-2
• Product Categories: (intermediate of pamidronate disodium);Delavirdine;API
• Mol File: 40391-99-9.mol
• Article Data: 30

Chemical Properties

• Melting Point: 226-228°C
• Boiling Point: 658.7 °C at 760 mmHg
• Flash Point: 352.2 °C
• Appearance: COA
• Density: 1.998 g/cm³
• Vapor Pressure: 3.79E-20mmHg at 25°C
• Refractive Index: 1.611
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Methanol (Very Slightly, Heated, Sonicated), Water (Slightly, Heated, Sonicated)
• Stability: Hygroscopic
• CAS DataBase Reference: Pamidronic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Pamidronic acid(40391-99-9)
• EPA Substance Registry System: Pamidronic acid(40391-99-9)

Safety Data

• Hazardous Substances Data: 40391-99-9(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

anticancer

InChI:InChI=1/C3H11NO7P2/c4-2-1-3(5,12(6,7)8)13(9,10)11/h5H,1-2,4H2,(H2,6,7,8)(H2,9,10,11)

Synthetic route

3-amino propanoic acid (107-95-9) → pamidronate (40391-99-9)

Conditions	Yield
With methanesulfonic acid; phosphorous acid; phosphorus trichloride at 65 - 70℃; Inert atmosphere;	99%
Stage #1: 3-amino propanoic acid With phosphorus trichloride In methanesulfonic acid at 80 - 85℃; Stage #2: With water In methanesulfonic acid at 105℃; for 4h;	85%
With phosphonic Acid; phosphorus trichloride In chlorobenzene at 100℃; for 3h; Inert atmosphere;	82%

[3-(benzyloxycarbonylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid (948317-73-5) → pamidronate (40391-99-9)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol for 24h;	90%

[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-hydroxy-1-phosphonopropyl]phosphonic acid (917092-03-6) → pamidronate (40391-99-9)

Conditions	Yield
With hydrazine hydrate In water at 20℃; for 0.5h;	67%
With hydrogenchloride In water for 5.5h; Reflux;

pamidronate (40391-99-9) → 3-amino-1-hydroxypropane-1,1-diphosphonic acid disodium salt

Conditions	Yield
With sodium methylate In ethanol	99.6%
With sodium methylate In methanol	97.9%
With sodium hydroxide In water

copper(II) carbonate + pamidronate (40391-99-9) + water (7732-18-5) → 2Cu(2+)*2H3NC2H4C(OH)(PO3)PO3H(2-)*H2O=[Cu2(H3NC2H4C(OH)(PO3)PO3H)2]*H2O

Conditions	Yield
In water High Pressure; equimol., heatd at 70°C in a closed flask for for 3 wk; crysts. decanted, dried (air); elem. anal.;	95%

formaldehyd (50-00-0) + pamidronate (40391-99-9) → olpadronate (63132-39-8)

Conditions	Yield
With formic acid for 17h; Heating;	92%

6-maleimidohexanoic acid N-hydroxylsuccinimide ester (55750-63-5) + pamidronate (40391-99-9) → (3‐{[6‐(2,5‐dioxo‐2,5‐dihydro‐1H‐pyrrol‐1‐yl)hexanoyl]amino}‐1‐hydroxypropane‐1,1‐diyl)bis(phosphonic acid)

Conditions	Yield
With sodium hydroxide In water; acetone at 20℃; pH=8 - 9;	88%

pamidronate (40391-99-9) → disodium-1,3-dihydroxypropane-1,1-diphosphonate

Conditions	Yield
With sodium nitrite In Na2 -salt; water	85%

pamidronate (40391-99-9) + water (7732-18-5) + copper(II) nitrate → 3Cu(2+)*2C3NH8P2O7(3-)*2H2O=Cu3(C3NH8P2O7)2*2H2O

Conditions	Yield
With NaOH In water High Pressure; a mixt. of Cu-contg. compd. (0.5 mmol), ligand (0.5 mmol) and water adjusted to pH 4.2 with NaOH aq. soln. was sealed in a Teflon-lined autoclave and heated at 160°C for 3 d; slow cooling to room temp.; crystals were filtered off and washed with water; elem. anal.;	85%

4-chloroquinazoline (5190-68-1) + pamidronate (40391-99-9) → [1-hydroxy-3-(quinazolin-4-ylamino)propane-1,1-diyl]bis(phosphonic acid)

Conditions	Yield
Stage #1: 4-chloroquinazoline; pamidronate With potassium carbonate In water at 95℃; for 24h; Reflux; Stage #2: With hydrogenchloride In water at 5℃; for 24h; pH=1;	82%

pamidronate (40391-99-9) + phenyl isothiocyanate (103-72-0) + formamide (77287-34-4, 77287-35-5, 60100-09-6) + triethylamine (121-44-8) → bis(triethylammonium) <1-hydroxy-3-(3-phenylthioureido)propylidene>bisphosphonate formamide

Conditions	Yield
In acetonitrile Ambient temperature;	77%

2-chloropyrimidine (1722-12-9) + pamidronate (40391-99-9) → [1-hydroxy-3-(pyrimidin-2-ylamino)propane-1,1-diyl]bis(phosphonic acid)

Conditions	Yield
Stage #1: 2-chloropyrimidine; pamidronate With potassium carbonate In water at 90 - 180℃; for 23h; Reflux; Stage #2: With hydrogenchloride In water at 5℃; for 48h; pH=1;	71%

zinc(II) nitrate (10196-18-6) + pamidronate (40391-99-9) + water (7732-18-5) → Zn(2+)*C3NH9P2O7(2-)*H2O=Zn(C3NH9P2O7)*H2O

Conditions	Yield
With NaOH In water High Pressure; a mixt. of Zn-contg. compd. (0.5 mmol), ligand (0.5 mmol) and water adjusted to pH 3.6 with NaOH aq. soln. was sealed in a Teflon-lined autoclave and heated at 160°C for 3 d; slow cooling to room temp.; crystals were filtered off and washed with water; elem. anal.;	70%

samarium(III) oxide + pamidronate (40391-99-9) → samarium(III) 3-ammonium-1-hydroxypropylidene-1,1-diphosphonate

Conditions	Yield
With hydrogenchloride In water at 160℃; for 48h; pH=0.65; Autoclave;	68%

pamidronate (40391-99-9) + [Pt(OSO3)(cis-1,4-diaminocyclohexane)(water)] (164654-62-0) + water (7732-18-5) → [(cis-Pt(1,4-diaminocyclohexane))2(3-ammonium-1-hydroxypropane-1,1-diylbisphosphonate)]HSO4*6water

Conditions	Yield
With Ba(OH)2*8H2O In water byproducts: BaSO4; addn. of barium hydroxide to aq. soln. of phosphonic acid deriv., addn. of aq. soln. of platinum compd., stirring at room temp. for 48 h; filtration, concg., addn. of aq. H2SO4 to pH 1, treating with acetone, keeping at 4°C for 2 h, filtration, drying in vac., elem. anal.;	65.1%

formaldehyd (50-00-0) + pamidronate (40391-99-9) → α-hydroxy-γ-propylidenediphosphonic acid

Conditions	Yield
With hydrogenchloride; phosphonic Acid In water at 115 - 120℃; for 3h;	64%

Nd2O5 + pamidronate (40391-99-9) → neodimium(III) 3-ammonium-1-hydroxypropylidene-1,1-diphosphonate

Conditions	Yield
With hydrogenchloride In water at 160℃; for 48h; pH=0.47; Autoclave;	63%

2-chloroquinazoline (6141-13-5) + pamidronate (40391-99-9) → [1-hydroxy-3-(quinazolin-2-ylamino)propane-1,1-diyl]bis(phosphonic acid)

Conditions	Yield
Stage #1: 2-chloroquinazoline; pamidronate With potassium carbonate In water at 90 - 180℃; for 22h; Reflux; Stage #2: With hydrogenchloride In water at 5℃; for 24h; pH=1;	62%

cobalt(II) nitrate hexahydrate + pamidronate (40391-99-9) → Co(2+)*C3NH9P2O7(2-)*H2O=Co(C3NH9P2O7)*H2O (898547-48-3)

Conditions	Yield
With NaOH In water High Pressure; a mixt. of Co-contg. compd. (0.5 mmol), ligand (0.5 mmol) and water adjusted to pH 2.8 with NaOH aq. soln. was sealed in a Teflon-lined autoclave and heated at 160°C for 3 d; slow cooling to room temp.; crystals were filtered off and washed with water; elem. anal.;	60%

manganese(II) nitrate hexahydrate + pamidronate (40391-99-9) → Mn(2+)*C3NH9P2O7(2-)*H2O=Mn(C3NH9P2O7)*H2O (898547-50-7)

Conditions	Yield
With NaOH In water High Pressure; a mixt. of Mn-contg. compd. (0.5 mmol), ligand (0.5 mmol) and water adjusted to pH 2.8 with NaOH aq. soln. was sealed in a Teflon-lined autoclave and heated at 160°C for 3 d; slow cooling to room temp.; crystals were filtered off and washed with water; elem. anal.;	60%

3-maleimidopropionic acid N-hydroxysuccinimide ester (55750-62-4) + pamidronate (40391-99-9) → (3‐{[3‐(2,5‐dioxo‐2,5‐dihydro‐1H‐pyrrol‐1‐yl)propanoyl]amino}‐1‐hydroxypropane‐1,1‐diyl)bis(phosphonic acid)

Conditions	Yield
With sodium hydroxide In water; acetone at 20℃; pH=8 - 9;	60%

Thiram (137-26-8) + pamidronate (40391-99-9) → disodium <3-(3,3-dimethylthioureido)-1-hydroxypropylidene>bisphosphonate trihydrate (140846-28-2)

Conditions	Yield
With triethylamine In methanol for 8h; Heating;	50%

nickel(II) nitrate hexahydrate + pamidronate (40391-99-9) → Ni2(C3NH10P2O7)4(H2O)2*2H2O

Conditions	Yield
In water High Pressure; a mixt. of Ni-contg. compd. (0.5 mmol), ligand (0.5 mmol) and water (pH 1.7) was sealed in a Teflon-lined autoclave and heated at 160°C for 3 d; slow cooling to room temp.; crystals were washed with water; elem. anal.;	50%

europium(III) oxide + pamidronate (40391-99-9) → europium(III) 3-ammonium-1-hydroxypropylidene-1,1-diphosphonate

Conditions	Yield
With hydrogenchloride In water at 160℃; for 36h; pH=0.58; Autoclave;	50%

4-chloro-2-phenylquinazoline (6484-25-9) + pamidronate (40391-99-9) → [1-hydroxy-3-((2-phenylquinazolin-4-yl)amino)propane-1,1-diyl]bis(phosphonic acid)

Conditions	Yield
Stage #1: 4-chloro-2-phenylquinazoline; pamidronate With potassium carbonate In water at 90 - 180℃; for 23h; Reflux; Stage #2: With hydrogenchloride In water at 5℃; for 48h; pH=1;	46%

pamidronate (40391-99-9) + pyridoxal 5'-phosphate (54-47-7) → ammonium salt 3-(N-[5'-phospho]pyridoxylamino)-1-hydroxypropyliden-1,1-bisphosphonic acid

Conditions	Yield
Stage #1: pamidronate; pyridoxal 5'-phosphate With triethylamine In ethanol; water at 20℃; for 1h; Stage #2: With sodium tetrahydroborate at 20℃; for 1h; Stage #3: With ammonia In water	44%

pamidronate (40391-99-9) + o-chlorobenzoyl chloride (609-65-4) → C10H14ClNO8P2 (790204-13-6)

Conditions	Yield
Stage #1: pamidronate; o-chlorobenzoyl chloride With sodium hydroxide In water at -10℃; for 6h; Stage #2: With hydrogenchloride In water pH=1;	41%

praseodymium oxide + pamidronate (40391-99-9) → praseodimium(III) 3-ammonium-1-hydroxypropylidene-1,1-diphosphonate

Conditions	Yield
With hydrogenchloride In water at 160℃; for 48h; pH=0.74; Autoclave;	41%

Upstream product

• 111-87-5 octanol 
• 917092-03-6 [3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-hydroxy-1-phosphonopropyl]phosphonic acid 
• 948317-73-5 [3-(benzyloxycarbonylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid 
• 107-95-9 3-amino propanoic acid 

Downstream Products

• 63132-39-8 olpadronate 
• 948317-73-5 [3-(benzyloxycarbonylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid 
• 775280-99-4 C₁₀H₁₅NO₈P₂ 
• 790204-13-6 C₁₀H₁₄ClNO₈P₂ 

Relevant articles and documents

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Efficient synthesis of pamidronic acid using an ionic liquid additive

An efficient method was developed for the synthesis of pamidronic acid involving the reaction of β-alanine with three equivalents of phosphorus trichloride and two equivalents of phosphorous acid at 75 °C in the presence of 0.3 or 0.6 equivalents of [BMIM][PF6] as an additive.

The synthesis of hydroxymethylenebisphosphonic- (dronic-) and acyl-ethoxycarbonyl-methylphosphonate derivatives

Recent results on the synthesis of substituted hydroxymethylenebisphosphonic acids (A and B), as well as acylated ethoxycarbonyl-methylphosphonate derivatives (C and D) are summarized. In the first part, solvent mixtures were applied in the preparation of known dronic acids, while in the second series of experiments, new acyl species were synthesized.

Copolymers having gem-bisphosphonate groupings

A copolymer includes a main hydrocarbon chain and side groups including carboxylic groups and polyoxyalkylate groups. The copolymer further includes gem-bisphosphonate groups. A composition, such as n admixture for suspensions of mineral particles, includes the copolymer. The copolymer can be used for fluidifying suspensions of mineral particles and maintaining the fluidity of such suspensions. The copolymer can also be used for reducing the sensitivity of hydraulic compositions to clays and alkaline sulfates.