2380-63-4

Basic information

• Product Name: 4-Aminopyrazolo[3,4-d]pyrimidine
• Synonyms: TIMTEC-BB SBB004205;1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLAMINE;1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE;4-AMINOPYRAZOLO[3,4-D]PYRIMIDINE;4-AMINO-1H-PYRAZOLO[3,4-D]PYRIMIDINE;ADENINE ANTIMETABOLITE;1H-Pyrazolo[3,4-d]pyrimidine, 4-amino-;4 APP
• CAS NO: 2380-63-4
• Molecular Formula: C₅H₅N₅
• Molecular Weight: 135.13
• EINECS: 219-174-6
• Product Categories: PYRIMIDINE;Pyridines, Pyrimidines, Purines and Pteredines;Heterocyclic Compounds;Heterocycles;Heterocycle-Pyrimidine series
• Mol File: 2380-63-4.mol
• Article Data: 42

Chemical Properties

• Melting Point: >325 °C(lit.)
• Boiling Point: 238.81°C (rough estimate)
• Flash Point: 244.382 °C
• Appearance: Light tan solid
• Density: 1.3795 (rough estimate)
• Vapor Pressure: 0.00118mmHg at 25°C
• Refractive Index: 1.7000 (estimate)
• Storage Temp.: -20°C Freezer
• PKA: 12.12±0.20(Predicted)
• Water Solubility: Insoluble in water.
• BRN: 5824
• CAS DataBase Reference: 4-Aminopyrazolo[3,4-d]pyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Aminopyrazolo[3,4-d]pyrimidine(2380-63-4)
• EPA Substance Registry System: 4-Aminopyrazolo[3,4-d]pyrimidine(2380-63-4)

Safety Data

• Hazard Codes: T
• Statements: 25-36/37/38-23/24/25
• Safety Statements: 26-36/37/39-45-22-36
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: UR0717000
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 2380-63-4(Hazardous Substances Data)

Usage

Chemical Properties

Light Tan Solid

Uses

Different sources of media describe the Uses of 2380-63-4 differently. You can refer to the following data:
1. 4-Amino-1H-pyrazolo[3,4-d]pyrimidine decreases serum cholesterol markedly in rats.
2. Decreases serum cholesterol markedly in rats.

InChI:InChI=1/C5H5N5/c6-4-3-1-9-10-5(3)8-2-7-4/h1-2H,(H3,6,7,8,9,10)

Synthetic route

3-Amino-4-cyanopyrazole (16617-46-2) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4)

Conditions	Yield
at 180℃;	100%
at 170℃; for 5h; Inert atmosphere;	94%
for 1h; Reflux;	93%

formamide (77287-34-4, 77287-35-5, 60100-09-6) + 3-amino-4-cyano-2H-pyrazole (16617-46-2) → 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4)

Conditions	Yield
at 180℃; Inert atmosphere;	95%
at 180℃; for 2h; Microwave irradiation;	93%
at 180℃; for 2h; Microwave irradiation;	93%

3-Amino-4-cyanopyrazole (16617-46-2) → 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4)

Conditions	Yield
In formamide	87%

3-Amino-4-cyanopyrazole (16617-46-2) → lH-pyrazolo[3,4-d]pyrimidin-4-ylamine + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4)

Conditions	Yield
In formamide	A n/a B 87%

formamidine acetic acid (3473-63-0) + 3-amino-4-cyano-2H-pyrazole (16617-46-2) → 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4)

Conditions	Yield
at 120℃; for 45h; Temperature; Concentration; Inert atmosphere;	84.1%
In ethanol for 5h; Reflux;	75%

N1,N1-dimethyl-N2-[4-cyanopyrazol-5-yl]formamidine (78972-81-3) → 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4)

Conditions	Yield
With ammonium hydroxide for 5h; Heating;	80%

4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 3-bromo-4-aminopyrazolo<3,4-d>pyrimidine (83255-86-1)

Conditions	Yield
With N-Bromosuccinimide In N,N-dimethyl-formamide at 60℃; for 3h;	100%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 80℃; for 5h;	92%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 60℃;	91%

4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (151266-23-8)

Conditions	Yield
With N-iodo-succinimide In N,N-dimethyl-formamide at 80℃;	100%
With N-iodo-succinimide In N,N-dimethyl-formamide at 80℃; for 5h;	98%
With N-iodo-succinimide In N,N-dimethyl-formamide for 12h;	97%

4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) + Hexafluoroacetone (684-16-2) → 2,2,4,4-tetrakis(trifluoromethyl)-2,8-dihydro<1,3,5>oxadiazino<3,4-c>pyrazolopyrimidine (125509-32-2)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 24h;	95%

di-tert-butyl dicarbonate (24424-99-5) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → C15H21N5O4

Conditions	Yield
With dmap In tetrahydrofuran at 20℃; Inert atmosphere;	90%

[(3aR,4S,6R, 6aR)-2,2-dimethyl-6-vinyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl] trifluoromethanesulfonate (1373333-65-3) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 1-((3aS,4R,6R,6aR)-2,2-dimethyl-6-vinyltetrahydro-3aHcyclopenta[d][1,3]dioxol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Conditions	Yield
Stage #1: 4-Aminopyrazolo<3,4-d>pyrimidin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Mitsunobu Displacement; Stage #2: [(3aR,4S,6R, 6aR)-2,2-dimethyl-6-vinyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl] trifluoromethanesulfonate In dichloromethane; N,N-dimethyl-formamide; mineral oil at 20℃; for 16h; Mitsunobu Displacement;	88%

N-iodo-succinimide (516-12-1) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (151266-23-8)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 12h;	86%
In N,N-dimethyl-formamide at 80℃; Concentration; Solvent;

4-phenoxyiodobenzene (2974-94-9) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (330786-24-8)

Conditions	Yield
With potassium tert-butylate In dimethyl sulfoxide at 120℃; for 24h; Inert atmosphere;	82%

Cyclopentyl bromide (137-43-9) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (21254-14-8)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 110℃;	80%

1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (6974-32-9) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → (2R,3R,4R,5R)-2-(4-amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate (854020-39-6)

Conditions	Yield
With boron trifluoride diethyl etherate In nitromethane for 2h; Heating;	79%
With boron trifluoride diethyl etherate In nitromethane for 1.5h; Reflux;	59%
With boron trifluoride diethyl etherate In nitromethane Reflux;	42%

C16H18F4O5S + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 1-((3aS,4R,6S,6aR)-6-(4-fluorobenzyl)-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Conditions	Yield
Stage #1: 4-Aminopyrazolo<3,4-d>pyrimidin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: C16H18F4O5S In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h;	78%

2'-Deoxyguanosine (961-07-9) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine (17318-21-7)

Conditions	Yield
With purine nucleoside phosphorylase at 50℃; pH=7; aq. phosphate buffer; Enzymatic reaction;	77%

copper (II) carbonate hydroxide + (carboxymethyl(4-methylbenzyl)amino)acetic acid (166826-77-3) + water (7732-18-5) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → [Cu2(N-(p-methylbenzyl)iminodiacetate)2(μ2-N1,N8-4-aminopyrazolo[3,4-d]pyrimidine)(water)2]*4water

Conditions	Yield
Stage #1: copper (II) carbonate hydroxide; (carboxymethyl(4-methylbenzyl)amino)acetic acid In water at 50℃; Stage #2: water; 4-Aminopyrazolo<3,4-d>pyrimidin In isopropyl alcohol for 1h;	75%

1-(tert-Butoxycarbonyl)-3-(methanesulfonyloxy)piperidine (129888-60-4) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → tert-butyl 3-(4-amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate (1374250-98-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃;	72%
Stage #1: 4-Aminopyrazolo<3,4-d>pyrimidin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5h; Stage #2: 1-(tert-Butoxycarbonyl)-3-(methanesulfonyloxy)piperidine In N,N-dimethyl-formamide; mineral oil at 100℃; for 16h;	50%

[1,3]-dioxolan-2-one (96-49-1) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 9-(2'-hydroxyethyl)adenine (100524-24-1)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide for 2h; Heating;	71%

copper (II) carbonate hydroxide + water (7732-18-5) + (carboxymethyl(4-fluorobenzyl)amino)acetic acid (1813-23-6) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → [Cu4(N-(p-fluorobenzyl)iminodiacetate)4(μ2-N8,N9-4-aminopyrazolo[3,4-d]pyrimidine)2(water)]*water

Conditions	Yield
Stage #1: copper (II) carbonate hydroxide; (carboxymethyl(4-fluorobenzyl)amino)acetic acid In water at 50℃; Stage #2: water; 4-Aminopyrazolo<3,4-d>pyrimidin In isopropyl alcohol for 1h;	65%

1-azido-2,3-epoxypropane (80044-09-3) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 1-(4-Amino-pyrazolo[3,4-d]pyrimidin-1-yl)-3-azido-propan-2-ol

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 8h;	64%

4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) + phenylboronic acid (98-80-6) → N-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (99973-41-8)

Conditions	Yield
With [2,2]bipyridinyl; copper diacetate; caesium carbonate In N,N-dimethyl-formamide at 60℃; for 12h; Chan-Lam Coupling;	62%

1-methyl-piperazine (109-01-3) + formaldehyd (50-00-0) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 1-(N-methylpiperazinomethyl)-4-(N-methylpiperazinomethylamino)pyrazolo<3,4-d>pyrimidine (83255-90-7)

Conditions	Yield
In water	60%

2'-deoxyuridine (951-78-0) + 4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) → 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine (17318-21-7)

Conditions	Yield
With purine nucleoside phosphorylase In dimethyl sulfoxide at 50℃; for 72h; pH=7; aq. phosphate buffer; Enzymatic reaction;	60%
at 37℃; for 16h; alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli, ammonium acetate buffer pH 5.7;

4-Aminopyrazolo<3,4-d>pyrimidin (2380-63-4) + benzyl alcohol (100-51-6) → N-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (58360-86-4)

Conditions	Yield
With samarium diiodide; potassium tert-butylate In tetrahydrofuran; toluene at 140℃; for 1.5h; Microwave irradiation; Inert atmosphere;	59%

Upstream product

• 315-30-0 Allopurinol 
• 16617-46-2 3-Amino-4-cyanopyrazole 
• 77287-34-4 formamide 
• 16617-46-2 3-amino-4-cyano-2H-pyrazole 
• 3258-05-7 4-amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine 
• 78972-81-3 N¹,N¹-dimethyl-N²-[4-cyanopyrazol-5-yl]formamidine 
• 5399-92-8 4-chloro-1H-pyrazolo[3,4-d]pyrimidine 
• 50-00-0 formaldehyd 
• 3473-63-0 formamidine acetic acid 

Downstream Products

• 130867-85-5 1-(2-Benzyloxy-1-benzyloxymethyl-ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine 
• 30129-51-2 4-bromopyrazolo<3,4-d>pyrimidine 
• 83255-86-1 3-bromo-4-aminopyrazolo<3,4-d>pyrimidine 
• 151266-23-8 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine 
• 17318-21-7 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine 
• 245450-02-6 4-(1H-pyrazolo[3,4-d]pyrimidine-4-yl)piperazin-1-carboxylic acid tert-butyl ester 
• 444020-01-3 4-amino-1-[3,5-bis-O-(2,4-dichlorophenylmethyl)-2-C-methyl-β-D-ribofuranosyl]-1H-pyrazolo[3,4-d]pyrimidine 
• 100524-24-1 9-(2'-hydroxyethyl)adenine 
• 854020-39-6 (2R,3R,4R,5R)-2-(4-amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate 
• 5444-61-1 1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine 
• 330792-72-8 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexan-1-one 
• 330792-74-0 3-iodo-1-((trans)-4-(4-methylpiperazin-1-yl)cyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 
• 330792-73-9 3-iodo-1-((cis)-4-(4-methylpiperazin-1-yl)cyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 
• 330792-81-9 3-(4-amino-3-methoxy-phenyl)-1-[4-(4-methyl-piperazin-1-yl)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine 

Relevant articles and documents

Discovery of novel selective Janus kinase 2 (JAK2) inhibitors bearing a 1H-pyrazolo[3,4-d]pyrimidin-4-amino scaffold

Janus kinases (JAKs) regulate various cancers and immune responses and are targets for the treatment of cancers and immune diseases. A new series of 1H-pyrazolo[3,4-d]pyrimidin-4-amino derivatives were synthesized and optimized by introducing a functional 3,5-disubstituted-1H-pyrazole moiety into the C-3 moiety of pyrazole template, and then were biologically evaluated as potent Janus kinase 2 (JAK2) inhibitors. Among these molecules, inhibitors 11f, 11g, 11h and 11k displayed strong activity and selectivity against the JAK2 kinase, with IC50 values of 7.2 nM, 6.5 nM, 8.0 nM and 9.7 nM, respectively. In particular, the cellular inhibitory assay and western blot analysis further support the JAK2 selectivity of compound 11g also in cells. Furthermore, compound 11g also exhibited potent inhibitory activity in lymphocytes proliferation assay and delayed hypersensitivity assay. Taken together, the novel JAK2 selective inhibitors discovered in this study may be potential lead compounds for new drug discovery via further development of more potent and selective JAK2 inhibitors.

Structure-based design and synthesis of 1H-pyrazolo[3,4-d]pyrimidin-4-amino derivatives as Janus kinase 3 inhibitors

Janus kinases (JAKs) regulate various inflammatory and immune responses and are targets for the treatment of inflammatory and immune diseases. Here we report the discovery and optimization of 1H-pyrazolo[3,4-d]pyrimidin-4-amino as covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Our optimization study gave compound 12a, which exhibited potent JAK3 inhibitory activity (IC50 of 6.2 nM) as well as excellent JAK kinase selectivity (>60-fold). In cellular assay, 12a exhibited potent immunomodulating effect on IL-2-stimulated T cell proliferation (IC50 of 9.4 μM). Further, compound 12a showed efficacy in delayed hypersensitivity assay. The data supports the further investigation of these compounds as novel JAKs inhibitors.

CYCLIC DI-NUCLEOTIDE COMPOUNDS AND METHODS OF USE

Disclosed are cyclic-di-nucleotide cGAMP analogs, methods of synthesizing the compounds, pharmaceutical compositions comprising the compounds thereof, and use of compounds and compositions in medical therapy.