5392-28-9

Basic information

• Product Name: Pyrimidinetetramine sulfate
• Synonyms: pyrimidinetetrayltetraamine sulphate;PYRIMIDINE-2,4,5,6-TETRAMINE SULPHATE;2,4,5,6-TETRAAMINIOPYRIMIDINE SULFATE;2,4,5,6-TETRAAMINO-PYRIMIDINE SULFATE SALT;2,4,5,6-TETRAAMINOPYRIMIDINE SULPHATE;2,4,5,6-Pyrimidinetetraamine sulfate salt;2,4,5,6-Tetramino Pyridine Sulfate;pyrimidinetetramine sulphate
• CAS NO: 5392-28-9
• Molecular Formula: C₄H₈N₆*H₂O₄S
• Molecular Weight: 238.23
• EINECS: 226-393-0
• Product Categories: FINE Chemical & INTERMEDIATES;Amines;(intermediate of methotrexate);Pyrimidines;Building Blocks;Heterocyclic Building Blocks;Aromatics;Heterocycles;Intermediates;Building Blocks;C4 to C5;Chemical Synthesis;Heterocyclic Building Blocks;Heterocycle-Pyrimidine series
• Mol File: 5392-28-9.mol
• Article Data: 0

Chemical Properties

• Melting Point: >300 °C(lit.)
• Boiling Point: 563.9 °C at 760 mmHg
• Flash Point: 329.4 °C
• Appearance: Ochre to brown/Crystalline Powder
• Density: 1.648g/cm3
• Vapor Pressure: 9.68E-13mmHg at 25°C
• Storage Temp.: Refrigerator
• Water Solubility: slightly soluble
• BRN: 3785189
• CAS DataBase Reference: Pyrimidinetetramine sulfate(CAS DataBase Reference)
• NIST Chemistry Reference: Pyrimidinetetramine sulfate(5392-28-9)
• EPA Substance Registry System: Pyrimidinetetramine sulfate(5392-28-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-37/39-26-36
• WGK Germany: 3
• RTECS: UV9738000
• TSCA: Yes
• Hazardous Substances Data: 5392-28-9(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow crystal powder

Uses

Intermediate in the production of Methotrexate

Purification Methods

Purify the salt by recrystallisation from H2O, 2N H2SO4 (20 parts, 67% recovery) or 0.1N H2SO4 (40 parts, 62% recovery), and dried in air. [UV: Konrad & Pfleiderer Chem Ber 103 722 1970, Malletta et al. J Am Chem Soc 69 1814 1947, Cavalieri et al. J Am Chem Soc 70 3875 1948, Beilstein 25 H 423, 25 III/IV 3106.]

InChI:InChI=1/C4H8N6.H2O4S/c5-1-2(6)9-4(8)10-3(1)7;1-5(2,3)4/h5H2,(H6,6,7,8,9,10);(H2,1,2,3,4)

Synthetic route

bis(3-hydroxyphenyl)ethane-1,2-dione (63192-57-4) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol sulfate

Conditions	Yield
In 3-methyl-phenol at 50 - 220℃; for 2 - 2.25h;	100%

carbon disulfide (75-15-0) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,6-diamino-9H-purine-8-thiol (462066-71-3)

Conditions	Yield
With sodium hydrogencarbonate In ethanol for 24h; Heating;	97%

3-hydroxyphenylglyoxal (70935-14-7) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → TG100110

Conditions	Yield
Stage #1: 3-hydroxyphenylglyoxal With hydrogenchloride; acetone oxime at 50℃; for 1h; pH=2 - 3; Stage #2: 2,4,5,6-tetraaminopyrimidine sulfate for 9h; Heating; Further stages.;	96.5%

3-hydroxyphenylglyoxal (70935-14-7) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + acetone oxime (127-06-0) → TG100110

Conditions	Yield
Stage #1: 3-hydroxyphenylglyoxal; acetone oxime With hydrogenchloride In methanol; water at 50℃; for 1h; pH=~ 2 - ~ 3; Stage #2: 2,4,5,6-tetraaminopyrimidine sulfate In water at 20℃; for 9h; Heating / reflux; Stage #3: With water; sodium hydrogencarbonate at 20℃; pH=~ 6 - ~ 7;	96.5%

bis(3-hydroxyphenyl)ethane-1,2-dione (63192-57-4) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → TG100-115 (677297-51-7)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; water	93.3%

1-butylsulfanylpropan-2-one (79948-21-3) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4-diamino-7-methylpteridine (4215-07-0)

Conditions	Yield
With piperidine In water at 20℃; for 268h;	93%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + thioacetic acid S-[5-(4-formylphenoxy)pentyl] ester (383424-15-5) → S-5-{4-[(2,4,6-triamino-N5-pyrimidinylidene)methyl]phenoxy}pentyl thioacetate

Conditions	Yield
With potassium carbonate In isopropyl alcohol Heating;	90%

1,10-phenanthroline-5,6-dione (27318-90-7) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4,5,6-tetraaminopyrimidine[3,2-a:2',3'-c]phenazine (928057-09-4)

Conditions	Yield
With acetic acid at 130℃; for 3h; Inert atmosphere;	87%
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With sodium hydroxide In water at 50℃; for 0.666667h; Stage #2: 1,10-phenanthroline-5,6-dione In ethanol; water for 3h; Reflux;	75%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + 1-chloro-1-benzamidoacetone (88297-80-7) → 2,4-diamino-7-methylpteridine (4215-07-0)

Conditions	Yield
With piperidine In water at 20℃; for 168h;	86%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + (1Z,4Z,9Z,15Z)-5,10,15,20-Tetrakis-(3,5-di-tert-butyl-phenyl)-porphyrin-2,3-dione → 8,11,14,17-tetrakis(3,5-di-tert-butylphenyl)-2,4-diaminopteridino[2,3,b]porphyrin

Conditions	Yield
In pyridine for 24h; Heating;	85%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + 9,10-phenanthrenequinone (84-11-7) → phenanthro[9,10-g]pteridine-11,13-diamine

Conditions	Yield
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With sodium hydroxide In water at 50℃; for 0.666667h; Stage #2: 9,10-phenanthrenequinone In ethanol; water for 3h; Reflux;	79%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + acenaphthene quinone (82-86-0) → acenaphtho[1,2-g]pteridine-9,11-diamine (38284-03-6)

Conditions	Yield
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With sodium hydroxide In water at 50℃; for 0.666667h; Stage #2: acenaphthene quinone In ethanol; water for 3h; Reflux;	78%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + 1-tosyl-4,5-dimethylimidazolin-2-one (54972-21-3) → 6,7-dimethyl-2,4-pteridine-2,4-diamine (1425-63-4)

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide at 20℃; for 264h;	77%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + 1-bromo-1-acetamidoacetone (65765-30-2) → 2,4-diamino-7-methylpteridine (4215-07-0)

Conditions	Yield
With piperidine; sodium carbonate In hydrogenchloride at 20℃; for 144h;	76%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + 4-Carboxybenzaldehyde (619-66-9) → TTPS

Conditions	Yield
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With barium(II) chloride at 60℃; for 0.166667h; Stage #2: 4-Carboxybenzaldehyde In benzene for 6h;	74%

2-butylthiopropanal (85296-31-7) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4-diamino-7-methylpteridine (4215-07-0)

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide at 20℃; for 720h;	72%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + benzil (134-81-6) → 2,4-diamino-6,7-diphenylpteridine (18181-93-6)

Conditions	Yield
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With sodium hydroxide In water at 50℃; for 0.666667h; Stage #2: benzil In ethanol; water for 3h; Reflux;	68%

pyridine-4-carbaldehyde (872-85-5) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4,6-triamino-5-(4-pyridylmethyleneamino)pyrimidine (74783-48-5)

Conditions	Yield
In sodium hydroxide at 90℃; for 0.5h;	64%

2,5-bis(5''-formyl-5',2''-bithienyl-2'-yl)-3,4-ethylenedioxythiophene (863684-19-9) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → C32H26N12O2S5

Conditions	Yield
In isopropyl alcohol	61%

benzo[1,3]dioxol-5-yl-acetyl fluoride (873436-93-2) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 8-(benzo[d][1,3]dioxol-5-ylmethyl)-9H-purine-2,6-diamine (873436-95-4)

Conditions	Yield
Stage #1: benzo[1,3]dioxol-5-yl-acetyl fluoride; 2,4,5,6-tetraaminopyrimidine sulfate With sodium hydroxide In water; N,N-dimethyl-formamide at 20 - 70℃; for 1.83333h; Stage #2: With sodium methylate In methanol at 90℃; for 18h;	56%

2,2'-thenil (7333-07-5) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 6,7-di(thiophen-2-yl)pteridine-2,4-diamine

Conditions	Yield
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With sodium hydroxide In water at 50℃; for 0.666667h; Stage #2: 2,2'-thenil In ethanol; water for 3h; Reflux;	55%

dihydroxyacetone (96-26-4) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4-diamino-6-(hydroxymethyl)pteridine (945-24-4)

Conditions	Yield
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With barium(II) chloride In water at 100℃; for 0.166667h; Stage #2: dihydroxyacetone With sodium acetate; DL-cysteine hydrochloride In water at 20℃; for 24h;	54%

(4-hydroxylphenyl)glyoxal (24645-80-5) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 4-(2,4-diaminopteridin-6-yl)phenol

Conditions	Yield
Stage #1: (4-hydroxylphenyl)glyoxal With hydroxylamine hydrochloride In methanol at 50℃; for 0.25h; Stage #2: 2,4,5,6-tetraaminopyrimidine sulfate In methanol for 3h; Heating; Further stages.;	50%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + furil (492-94-4) → 6,7-di(furan-2-yl)pteridine-2,4-diamine

Conditions	Yield
Stage #1: 2,4,5,6-tetraaminopyrimidine sulfate With sodium hydroxide In water at 50℃; for 0.666667h; Stage #2: furil In ethanol; water for 3h; Reflux;	42%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + S-(6-(4-formylphenoxy)hexyl)ethanethioate (248588-29-6) → Thioacetic acid S-[6-(4-{[(E)-2,4,6-triamino-pyrimidin-5-ylimino]-methyl}-phenoxy)-hexyl] ester

Conditions	Yield
With potassium carbonate In isopropyl alcohol Heating;	27%

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + benzoic acid (65-85-0) → 2,6-diamino-8-phenylpurine (26216-55-7)

Conditions	Yield
With PPA; Polyphosphoric acid (PPA) at 170℃; for 1h;	10%

dihydroxyacetone (96-26-4) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4-diamino-6-(hydroxymethyl)pteridine hydrochloride (73978-41-3)

Conditions	Yield
With ammonium hydroxide; l-cysteine hydrochloride; oxygen; ammonium chloride; barium(II) chloride 1.) H2O, 90 deg C, 15 min, 2.) H2O, RT, 45 h; Yield given. Multistep reaction;

1,1-dibromopropan-2-one (867-54-9) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4-diamino-7-methylpteridine (4215-07-0) + 2,4-diamino-6-methylpteridine (708-74-7)

Conditions	Yield
With sodium hydrogensulfite In water at 80℃; for 5.5h; Product distribution; further cyclizating agents;

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + 1-(benzenesulfonyl)-4-methylimidazolin-2-one (79614-35-0) → 2,4-diamino-7-methylpteridine (4215-07-0) + 2,4-diamino-6-methylpteridine (708-74-7)

Conditions	Yield
With piperidine In water for 550h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) + 1-(4'-chlorobenzenesulfonyl)-4-methylimidazolin-2-one (79614-36-1) → 7-methylpterin (13040-58-9) + 2-amino-6-methylpteridin-4(1H)-one (708-75-8)

Conditions	Yield
With piperidine; potassium hydroxide 1.) water, 20 deg C, 7 d, 2.) heating; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

Downstream Products

• 4215-07-0 7-methyl-2,4-diaminopteridine 
• 73978-41-3 2,4-diamino-6-(hydroxymethyl)pteridine hydrochloride 
• 708-74-7 2,4-diamino-6-methylpteridine 
• 13040-58-9 7-methylpterin 
• 708-75-8 2-amino-6-methylpteridin-4(1H)-one 
• 945-24-4 2,4-diamino-6-(hydroxymethyl)pteridine 
• 39944-62-2 2,4,5,6-tetraamino-pyrimidine dihydrochloride 
• 925705-73-3 TG₁₀₀₁₁₀ 
• 59-05-2 N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid 
• 18181-93-6 2,4-diamino-6,7-diphenylpteridine 
• 873436-95-4 8-(benzo[1,3]dioxol-5-ylmethyl)-2-aminoadenine 
• 91-18-9 pteridine 
• 677297-51-7 TG100-115 
• 1425-63-4 6,7-dimethyl-2,4-pteridine-2,4-diamine