4,5-Diamino-6-hydroxy-2-mercaptopyrimidine

Cat.NO.:A273422 Purity:85%

Product Details of [ 1004-76-8 ]

CAS No. :	1004-76-8
Formula :	C₄H₆N₄OS
M.W :	158.18
SMILES Code :	NC1=C(N)C(O)=NC(S)=N1
MDL No. :	MFCD00040963
InChI Key :	QYSWOQHLIDKEOL-UHFFFAOYSA-N
Pubchem ID :	1201437

Safety of [ 1004-76-8 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 1004-76-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	3.0
Molar Refractivity	40.12
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	136.85 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.9
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	-0.36
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.35
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.	-1.19
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	-0.53
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.31

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.04
Solubility	14.5 mg/ml ; 0.0916 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.	-2.05
Solubility	1.41 mg/ml ; 0.00888 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	-0.46
Solubility	55.1 mg/ml ; 0.348 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	Yes
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.	-7.52 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	1.0
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	1.0 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)	2.0

Application In Synthesis of [ 1004-76-8 ]

* 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.

Upstream synthesis route of [ 1004-76-8 ]
Downstream synthetic route of [ 1004-76-8 ]

[ 1004-76-8 ] Synthesis Path-Upstream 1~2

1
[ 100-52-7 ]
[ 1004-76-8 ]
[ 14892-97-8 ]

Yield	Reaction Conditions	Operation in experiment
39%	With acetic acid In N,N-dimethyl-formamide for 3 h; Reflux	Method A. A solution of benzaldehyde (466 mg, 4.4 mmol) in DMF (1.5 mL) and acetic acid (0.5 mL) was added to solid 4,5-diamino-6-hydroxy-2-mercaptopyrimidine (316 mg, 2.0 mmol). The reaction mixture was heated under reflux for 3 hours, then cooled to room temperature, and added slowly to 10 mL of ice water. A yellow solid precipitated out which was collected by vacuum filtration and air dried. The solid was dissolved in 60 mL of chloroform, filtering the chloroform solution to remove insoluble material. The entire chloroform solution was loaded onto a silica gel column packed in dichloromethane. The column was eluted with 2:1 dichloromethane : ethyl acetate, and the first yellow band was collected. The solvent was removed to yield 257 mg (0.77 mmol, 39 percent). ¹H NMR (DMSO) δ 13.42 (br. s, 1H), 12.82 (br.s, 1H), 7.43-7.34 (m, 10H). ¹³C NMR (DMSO) δ 175.7, 158.5, 155.9, 149.1, 147.0, 137.7, 137.1, 129.8 (C-H), 129.7 (C-H), 129.5 (C-H), 128.8 (C-H), 128.3 (C-H), 128.2 (C-H), 127.2. HRMS Calcd for C₁₈H₁₃N₄OS (M+H⁺) 333.0810. Found: 333.0802. IR (Nujol): 3407 (br), 1698, 1633, 1552, 1126, 722, 695, 665. M.P. 200-203 (d.). UV/Vis: λ_max 380 nm, ε = 12,000 M^-1cm^-1.

References:

[1] Tetrahedron Letters, 2016, vol. 57, # 29, p. 3204 – 3207.

2
[ 1004-76-8 ]
[ 134-81-6 ]
[ 14892-97-8 ]

References:

[1] Bulletin de la Societe Chimique de France, 1945, vol. <5> 12, p. 78,82.

Yield	Reaction Conditions	Operation in experiment
14%		General procedure: A solution of <strong>[121584-52-9]acetyl-CsA-aldehyde</strong> (compound 1; 10 mg; 8 tmol) and 4,5-diamino-6-hydroxy-2-mercaptopyrimidine (3.2 mg; 18 jtmol) in DMF (1 ml) was stirred at 100 C. overnight. After removal of the solvent in vacuum, acetate hydrolysis, work-up of the reaction mixture and the purification of compound 17 were performed in the same manner as described for compound 14. Yield: 1.5 mg (14%); A solution of <strong>[121584-52-9]acetyl-CsA-aldehyde</strong> (compound 1; 20 mg)and tert-butyl-3-(3,4-diamino-phenyl)-acrylate (50 mg; 0.21mmol) in MeOH (1 ml) was shacked at room temperature tillcompletion of the reaction (control by analytical HPLC).The reaction mixture was cooled at 5 C., 0.2M NaOH (1ml) was added and the reaction mixture was shacked at 5C. till completion of the hydrolysis (control by analytical HPLC). Then, the reaction mixture was acidified with 18% chiorhydric acid (100 pi) and the product was purified by preparative HPLC. Yield: 5 mg (22.2%).

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