(5-Amino-1H-pyrazol-3-yl)methanol

Cat.NO.:A290690 Purity:95%

Product Details of [ 1000895-26-0 ]

CAS No. :	1000895-26-0
Formula :	C₄H₇N₃O
M.W :	113.12
SMILES Code :	OCC1=NNC(N)=C1
MDL No. :	MFCD10000831
InChI Key :	NZORXPUYHVZTQG-UHFFFAOYSA-N
Pubchem ID :	55263172

Safety of [ 1000895-26-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 1000895-26-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	8
Num. arom. heavy atoms	5
Fraction Csp3	0.25
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	3.0
Molar Refractivity	29.12
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	74.93 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.12
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-0.98
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.66
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-1.12
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.18
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.49

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-0.32
Solubility	54.1 mg/ml ; 0.478 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-0.11
Solubility	88.3 mg/ml ; 0.78 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.65
Solubility	25.5 mg/ml ; 0.225 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.69 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12’782’590 molecules and tested on 40 external molecules (r² = 0.94)	1.69

Application In Synthesis of [ 1000895-26-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 1000895-26-0 ]

[ 1000895-26-0 ] Synthesis Path-Downstream 1~6

1
[ 3934-20-1 ]
[ 1000895-26-0 ]
[5-[(2-chloropyrimidin-4-yl)amino]-2H-pyrazol-3-yl]methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine; In ethanol; at 40.0℃; for 96.0h;	[5-[(2-chloropyrimidin-4-yl)amino]-2H-pyrazol-3-yl]methanol, used as starting material, was prepared as follows: ;a) A mixture of <strong>[1000895-26-0](5-amino-2H-pyrazol-3-yl)methanol</strong> (2.5 1 g, 22.2 mmol) and 2,4-dichloropyrimidine (3.0 g, 20.1 mmol) and di-iso-propylethylamine (4.21 ml, 24.2 mmol) in ethanol (60 ml) was stirred at 40 C. for 4 days. The resultant precipitate was filtered, washed with ethanol and then with diethyl ether and then dried under vacuum to leave [5-[(2-chloropyrimidin-4-yl)amino]-2H-pyrazol-3-yl]methanol (3.1 g, 68% yield). 1H NMR (300 MHz, DMSO): 4.46 (d, 2H), 5.28 (d, 1H), 6.25 (s, 1H), 7.15 (s, 1H), 8.16 (s, 1H), 10.32 (s, 1H), 12.32 (s, 1H).MS: m/z 226 (MH+).

References: [1]Patent: US2008/4302,2008,A1 .Location in patent: Page/Page column 50.

2
5-nitropyrazole-3-carboxylic acid [ No CAS ]
[ 1000895-26-0 ]

Yield	Reaction Conditions	Operation in experiment
57%	With ammonium formate;palladium 10% on activated carbon; In ethanol; at 140.0℃; for 0.166667h;Microwave irradiation;	ii) Ammonium formate (0.551 g, 8.74 mmol) was added, in one portion, to a solution of (5-nitro-1H-pyrazol-3-yl)methanol (0.50 g, 3.49 mmol) in ethanol (14 ml). The mixture was blanketed with argon and 10% palladium on carbon (50 mg) was added. The vial was then sealed and heated in a microwave to 140 C. for 10 minutes. The mixture was filtered and the residue was washed with a 1:1 mixture of ethyl acetate:ethanol (20 ml). The filtrate was evaporated and the residue purified by chromatography on silica eluting with a 0-30% mixture of methanol in ethyl acetate to give (5-amino-2H-pyrazol-3-yl)methanol (0.225 g, 57% yield). 1H NMR (400 MHz, DMSO): 4.27 (d, 2H), 4.53 (s, 2H), 4.95 (t, 1H), 5.29 (s, 1H), 11.20 (s, 1H).

References: [1]Patent: US2008/4302,2008,A1 .Location in patent: Page/Page column 50.

3
[ 632365-54-9 ]
[ 1000895-26-0 ]

Yield	Reaction Conditions	Operation in experiment
		Under argon, lithium borohydride (2M in THF, 84.2 ml) was added dropwise to a stirred solution of methyl 5-aminopyrazole-3-carboxylate (9.5 g) in tetrahydrofuran (300 ml). The resultant mixture was heated to reflux for 16 hours. The mixture was cooled and methanol was added dropwise to quench residual reducing agent. The mixture was evaporated. Methanol (200 ml) was added to the residue and insoluble salts were removed by filtration. The filtrate was evaporated and the residue was purified by column chromatography on silica using a solvent gradient of 9:1 to 4:1 of methylene chloride and methanol as eluent. There was thus obtained 3-amino-5-hydroxymethyl-li?-pyrazole (5.6 g) 1H NMR: (DMSOd6) 4.27 (s, 2H)5 4.3-5.2 (2 br s, 3H), 5.29 (s, IH).

References: [1]Patent: WO2007/99326,2007,A1 .Location in patent: Page/Page column 116.

4
[ 1000895-26-0 ]
[ 285984-47-6 ]
[ 1415484-35-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7523 – 7529.

5
[ 3764-01-0 ]
[ 1000895-26-0 ]
(3-((2,6-dichloropyrimidin-4-yl)amino)-1H-pyrazol-5-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With N-ethyl-N,N-diisopropylamine; In ethanol; at 20.0℃; for 12.0h;	To a mixture of 2,4,6-trichloropyrimidine (8.0 g, 43.7 mmol) and <strong>[1000895-26-0](3-amino-1H-pyrazol-5-yl)methanol</strong> (7.4 g, 65.4 mmol) in EtOH (80 mL) was added DIPEA (11.3 g, 87.2 mmol). The reaction mixture was stirred at 20 C. for 12 h and filtered to give the title intermediate (6.5 g, 57% yield) as a white solid. (m/z): [M+H]+ calcd for C8H7Cl2N5O 260.00 found 260.0.

References: [1]Patent: US2017/312280,2017,A1 .Location in patent: Paragraph 0270-0271.

6
[ 1000895-26-0 ]
[ 13154-24-0 ]
5-(((triisopropylsilyl)oxy)methyl)-1H-pyrazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With 1H-imidazole; In 1-methyl-pyrrolidin-2-one; at 22.0℃;	To a 100 mL flask was added <strong>[1000895-26-0](3-amino-1H-pyrazol-5-yl)methanol</strong> (5.8 g, 51.3 mmol), 1-methyl-2-pyrrolidinone (58.0 mL) and imidazole (4.54 g, 66.7 mmol) followed by triisopropylsilyl chloride (11.95 mL, 56.4 mmol).The reaction mixture was stirred at 22 C. overnight and then EtOAc (145 mL) and water (145 mL) were added. The layers were separated and the organic layer was washed with water (145 mL) and brine (15%, 100 mL), dried over Na2SO4, and evaporated under reduced pressure to provide the title intermediate (13.33 g, 49.5 mmol, 96% yield) HPLC Method A Retention time 19.00 min.

References: [1]Patent: US2017/312280,2017,A1 .Location in patent: Paragraph 0311; 0312; 0313.

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