4-Amino-2-(hydroxymethyl)pyridine

Cat.NO.:A192561 Purity:95%

Product Details of [ 100114-58-7 ]

CAS No. :	100114-58-7
Formula :	C₆H₈N₂O
M.W :	124.14
SMILES Code :	OCC1=NC=CC(N)=C1
MDL No. :	MFCD11100581
InChI Key :	ZBKZWFGHOALGNP-UHFFFAOYSA-N
Pubchem ID :	23564158

Safety of [ 100114-58-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 100114-58-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.17
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	2.0
Molar Refractivity	34.77
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	59.14 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.75
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	-0.68
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.01
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.	-0.75
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	0.49
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.04

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-0.61
Solubility	30.6 mg/ml ; 0.246 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.	-0.09
Solubility	101.0 mg/ml ; 0.818 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	-1.45
Solubility	4.39 mg/ml ; 0.0354 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.	-7.54 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	1.0
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)	1.33

Application In Synthesis of [ 100114-58-7 ]

* 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 [ 100114-58-7 ]

[ 100114-58-7 ] Synthesis Path-Downstream 1~6

1
[ 100377-37-5 ]
[ 100114-58-7 ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; potassium hydroxide; for 2.0h;Reflux;	Step 2. (4-Amino-2-pyridyl)methanol: N-[2-(Hydroxymethyl)-4-pyridyl]acetamide (0.050 g, 0.30 mmol) was dissolved in EtOH and treated with KOH (0.033 g, 0.60 mmol). The solution was heated at reflux for 2 h. The solution was concentrated under a stream of nitrogen gas and the residue dissolved with DCM. The organic solution was dried (Na2S04) and concentrated to give the title compound. 1H NMR (DMSO-d6) delta 7.86 (d, 1H), 6.60 (d, 1H), 6.30 (dd, 1H), 5.97 (s, 2H), 5.22 (s, 1H), 4.34 (s, 2H).

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1959,vol. 79,p. 487,491.

Chemisches Zentralblatt,1959,vol. 130,p. 18028.
[2]Patent: WO2012/142329,2012,A1 .Location in patent: Page/Page column 73-74.

2
[ 1918-02-1 ]
[ 100114-58-7 ]
[ 100047-36-7 ]
4-amino-3-chloro-pyridine-2-carboxylic acid [ No CAS ]
4-amino-6-chloropyridine-2-carboxylic acid [ No CAS ]

References: [1]Chemosphere,2001,vol. 43,p. 1109 – 1117.

3
[ 99068-72-1 ]
[ 100114-58-7 ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1959,vol. 79,p. 487,491.

Chemisches Zentralblatt,1959,vol. 130,p. 18028.

4
[ 63071-10-3 ]
[ 100114-58-7 ]

References: [1]Patent: WO2012/142329,2012,A1 .

5
[ 100114-58-7 ]
methyl 3-chloro-1-methyl-4-[[(1R)-2,2,2-trifluoro-1-methyl-ethyl]sulfamoyl]pyrrole-2-carboxylate [ No CAS ]
3-chloro-N-[2-(hydroxymethyl)-4-pyridyl]-1-methyl-4-[[(1R)-2,2,2-trifluoro-1-methylethyl]sulfamoyl]pyrrole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
249 mg	With lithium hexamethyldisilazane; In tetrahydrofuran; at 20.0℃;	Methyl 3-chloro-l-methyl-4-[[(lR)-2,2,2-trifluoro-l-methyl-ethyl]sulfamoyl]pyrrole-2- carboxylate (400 mg, 0.57 mmol) and <strong>[100114-58-7](4-aminopyridin-2-yl)methanol</strong> (157 mg, 1.26 mmol) were dissolved in dry THF (5 mL). Lithium bis(trimethylsilyl)amide (1M in THF) (3.4 mL, 1 M, 3.4 mmol) was added drop wise and the reaction mixture was stirred overnight at room temperature. The reaction mixture was next quenched with sat. NH4C1 (10 mL). The organic layer was removed and the aqueous layer extracted with CH2CI2 (2 X 5 mL). The combined organic layers were evaporated to dryness and the residue was purified on silica using a heptane to EtOAc gradient yielding 3-chloro-N-[2-(hydroxymethyl)-4-pyridyl]-l-methyl-4-[[(lR)-2,2,2- trifluoro-l-methyl-ethyl]sulfamoyl]pyrrole-2-carboxamide (249 mg) as an off-white powder after trituration with diisopropylether. Method B: Rt: 0.81 min. m/z: 439 (M-H)” Exact mass: 440.1. 1H NMR (400 MHz, DMSO-d6) 5 ppm 1.19 (d, J=7.0 Hz, 3 H), 3.78 (s, 3 H), 3.92 – 4.05 (m, 1 H), 4.53 (d, J=5.7 Hz, 2 H), 5.42 (t, J=5.8 Hz, 1 H), 7.55 (dd, J=5.5, 2.0 Hz, 1 H), 7.68 (s, 1 H), 7.79 (d, J=1.5 Hz, 1 H), 8.38 (d, J=5.5 Hz, 1 H), 8.50 (br. s., 1 H), 10.69 (s, 1 H). DSC: From 30 to 300 C at 10C/min, peak 233.9 C. 3-chloro-N-[2-(hydroxymethyl)-4-pyridyl]-l- methyl-4-[[(lR)-2,2,2-trifluoro-l-methyl-ethyl]sulfamoyl]pyrrole-2-carboxamide (181 mg, 0.41 mmol) was dissolved in THF (5 mL). (Diethylamino)sulfur trifluoride (108.5 mu, 0.82 mmol) was added and the reaction mixture was stirred overnight at room temperature. The volatiles were removed under reduced pressure and the residue was purified via prep. HPLC (Stationary phase: RP XBridge Prep C18 OBD-IotaOmicronmuiotaeta, 30x150mm, Mobile phase: 0.25% (0700) NH4HCO3 solution in water, MeOH) yielding 3-chloro-N-[2-(fluoromethyl)-4-pyridyl]-l- methyl-4-[[(lR)-2,2,2-trifluoro-l-methyl-ethyl]sulfamoyl]pyrrole-2-carboxamide (11.2 mg). Method B: Rt: 0.97 min. m/z: 441.1 (M-H)” Exact mass: 442.0. 1H NMR (400 MHz, (0701) CHLOROFORM-d) delta ppm 1.39 (d, J=6.8 Hz, 3 H), 3.93 – 3.99 (m, 1 H), 4.00 (s, 3 H), 5.49 (d, J=46.9 Hz, 2 H), 7.37 (s, 1 H), 7.58 – 7.64 (m, 2 H), 8.52 (d, J=5.3 Hz, 1 H).

References: [1]Patent: WO2015/118057,2015,A1 .Location in patent: Page/Page column 99.

6
[ 67-56-1 ]
[ 100114-58-7 ]
nickel dichloride [ No CAS ]
[Ni₄(2-(hydroxymethyl)-4-aminopyridine)₄Cl₄(MeOH)₄] [ No CAS ]

References: [1]Dalton Transactions,2018,vol. 47,p. 8865 – 8869.

Details

Reviews

There are no reviews yet.

Be the first to review “4-Amino-2-(hydroxymethyl)pyridine”

Products