755039-55-5|(R)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one| Ambeed

Structure of 755039-55-5

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Quality Control of [ 755039-55-5 ] Purity: 95% SDS Specification

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Product Details of [ 755039-55-5 ]

CAS No. :	755039-55-5
Formula :	C₁₄H₁₉ClN₄O
M.W :	294.78
SMILES Code :	O=C1N(C)C2=CN=C(Cl)N=C2N(C3CCCC3)[C@@H]1CC
MDL No. :	MFCD10698781
InChI Key :	RDOMCFLYXZACAX-SNVBAGLBSA-N
Pubchem ID :	24820413

Safety of [ 755039-55-5 ]

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

Computational Chemistry of [ 755039-55-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	20
Num. arom. heavy atoms	6
Fraction Csp3	0.64
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	86.14
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	49.33 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	3.02
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	2.98
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.87
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.	1.91
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	1.86
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.33

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.64
Solubility	0.0683 mg/ml ; 0.000232 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.68
Solubility	0.0617 mg/ml ; 0.000209 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	-3.48
Solubility	0.0978 mg/ml ; 0.000332 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	Yes
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	Yes
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	Yes
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.	-5.98 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	0.0
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<0.0
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)	3.26

Application In Synthesis of [ 755039-55-5 ]

* 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 [ 755039-55-5 ]

[ 755039-55-5 ] Synthesis Path-Downstream 1~35

1
[ 108-11-2 ]
[ 755039-55-5 ]
[ 41608-64-4 ]
[ 957855-48-0 ]

Yield	Reaction Conditions	Operation in experiment
53%	With toluene-4-sulfonic acid; for 5.0h;Heating / reflux;	(7/?)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7H-pteridin-6-one (WO2004076454; 200 mg,0.68 mmol), methyl 4-amino-3-methoxy-benzoate (123 mg, 0.68 mmol) andp-toluenesulfonic acid (323 mg, 1.70 mmol) were suspended in (2i?/5)-4-methyl-2-pentanol (1 mL) and heated at reflux for 5 h, allowing the MeOH evaporate during the reaction. The reaction mixture was cooled and loaded onto an SCX-2 column and washed with MeOH (40 mL). The crude product was then eluted from the SCX-2 column with NH3(40 mL, 7M in MeOH) and the volatiles removed under reduced pressure. Purification by column chromatography (SiO2, eluent gradient 0-100% EtOAc in /s°-hexane) afforded the title compound (185 mg, 53%) as a gum. 1H NMR (400 MHz, DMSO-d6) deltaH 0.77 (t, 3H), 0.91 (dd, 6H), 1.29 (d, 3H), 1.37 - 1.48 (m, IH), 1.55 - 2.08 (m, 12H), 3.30 (s, 3H), 3.95 (s, 3H), 4.25 (dd, IH), 4.37 (quintet, IH), 5.09 - 5.17 (m, IH), 7.49 (d, IH), 7.58 (dd, IH), 7.71 (s, IH), 7.86 (s, IH), 8.51 (dt, IH); MS m/z 510 [M+H]+.

References: [1]Patent: WO2007/135374,2007,A1 .Location in patent: Page/Page column 47.

2
[ 755039-55-5 ]
[ 957855-54-8 ]
[ 957855-51-5 ]

Yield	Reaction Conditions	Operation in experiment
66%	With toluene-4-sulfonic acid; In Methyl isobutyl carbinol; for 12.0h;Heating / reflux;	(7lambda)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7H-pteridin-6-one (WO2004076454; 281 mg, 0.95 mmol)), 4-amino-2-fluoro-N-(l-methyl-4-piperidyl)benzamide (Intermediate 5; 263 mg, 1.05 mmol) and />-toluenesulfonic acid (452 mg, 2.38 mmol) were suspended in (2R/S)-4- methyl-2-pentanol (10 mL) and heated at reflux for 12 h. The reaction mixture was cooled and loaded onto an SCX-2 column then washed with MeOH (20 mL). The crude compound was eluted from the SCX-2 column with NH3 (40 mL, 7M in MeOH). Purification by column chromatography (SiO2, eluting with MeOH) afforded a gum. The gum was dissolved in DCM and filtered to afford the title compound (319 mg, 66%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) deltaH 0.75 (tr, 3H), 1.60-2.10 (m, 14H), 2.74 (s, 3H), 3.09 (m, 2H), 3.22 (s, 3H), 3.39 (m, 2H), 4.03 (m, IH), 4.20 (m, IH), 4.41 (s, IH), 7.38 (d, IH), 7.53 (tr, IH), 7.78 (s, IH), 7.89 (d, IH); MS m/z 510 [M+H]+.

References: [1]Patent: WO2007/135374,2007,A1 .Location in patent: Page/Page column 48.

3
[ 755039-55-5 ]
[ 946826-31-9 ]
[ 957855-87-7 ]

Yield	Reaction Conditions	Operation in experiment
24%	With toluene-4-sulfonic acid; In Methyl isobutyl carbinol; for 24.0h;Heating / reflux;	(7/?)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7H-pteridin-6-one (WO2004076454, 250 mg, 0.85 mmol), 3-ethoxy-iV-(l-methyl-4-piperidyl)-4-amino-benzamide (Intermediate 20; 236 mg, 0.85 mmol), and p-toluenesulfonic acid (405 mg, 2.13 mmol) were dissolved in (2R/S)-4- methyl-2-pentanol (4 mL) and stirred at reflux for 24 h. The reaction mixture was then cooled, and poured onto SCX-2 column. The SCX-2 column was washed with MeOH (20 mL) and the crude product was eluted from the SCX-2 column with NH3 (20 mL, 7M in MeOH). Purification by column chromatography (SiO2, gradient eluent: 0-10% NH3 [7M in MeOH] in DCM) afforded the title compound (109 mg, 24%) as a solid. 1H NMR (400 MHz, CDCl3) deltaH 0.88 (t, 3H), 1.50 (t, 3H), 1.60 - 1.76 (m, 6H), 1.81 - 1.91 (m, 4H), 1.98 - 2.19 (m, 6H), 2.30 (s, 3H), 2.82 (d, 2H), 3.33 (s, 3H), 3.95 - 4.02 (m, IH), 4.21 (q, 3H), 4.40 - 4.45 (m, IH), 5.89 (d, IH), 7.21 - 7.24 (m, IH), 7.40 (d, IH), 7.61 (s, IH), 7.68 (s, IH), 8.54 (d, IH); MS m/z 536 [M+H]+.

References: [1]Patent: WO2007/135374,2007,A1 .Location in patent: Page/Page column 58.
[2]Journal of Medicinal Chemistry,2019,vol. 62,p. 2618 - 2637.

4
[ 755039-54-4 ]
[ 74-88-4 ]
[ 755039-55-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In ISOPROPYLAMIDE; at -10 - 20℃; for 0.833333h;	25.0 g of the compound Z3d and 6.5 mL (0.1 mol) methyl iodide were placed in 250 mL dimethylacetamide and at -10 C. 3.8 g (0.95 mol) sodium hydride were added as a 60% dispersion in mineral oil. The mixture was stirred for 20 min. at 0 C., then 30 min. at ambient temperature and finally ice was added. The reaction mixture was evaporated down and combined with 300 mL water. The precipitate formed was suction filtered and washed with petroleum ether. Yield: 23.0 g of a compound Z3e (colourless solid)
	With sodium hydride; In ISOPROPYLAMIDE; at -10 - 20℃; for 0.833333h;	25.0 g of the compound Z3d and 6.5 mL (0.1 mol) methyl iodide are placed in 250 mL dimethylacetamide and at -100C 3.8 g (0.95 mol) sodium hydride as a 60% dispersion in mineral oil is added. It is stirred for 20 min at 00C, then for 30 min at ambient temperature and finally ice is added. The reaction mixture is evaporated down and combined with 300 mL water. The precipitate formed is suction filtered and washed with petroleum ether. Yield: 23.0 g of a compound Z3e (colourless solid)
	With sodium hydride; In ISOPROPYLAMIDE; at 0 - 20℃; for 0.833333h;	25.0 g of the compound Z3d and 6.5 mL (0.1 mol) methyl iodide are placed in 250 mL dimethylacetamide and at -10 C. 3.8 g (0.95 mol) sodium hydride are added as a 60% dispersion in mineral oil. The mixture is stirred for 20 min. at 0 C., then 30 min. at ambient temperature and finally ice is added. The reaction mixture is evaporated down and combined with 300 mL water. The precipitate formed is suction filtered and washed with petroleum ether. Yield: 23.0 g of a compound Z3e (colourless solid)

	With sodium hydride; In ISOPROPYLAMIDE; at 4 - 20℃; for 7.0h;	Preparation of Compound 9; 38 g (0.95 mol) sodium hydride (60% dispersion in mineral oil) are added batchwise to a solution of 264 g (0.94 mol) of 8 and 161 g (1.13 mol) methyl iodide in 2 L dimethylacetamide at 4-10 C. within one hour. The cooling bath is removed and the mixture is allowed to come up to 20 C. within 2 hours. It is cooled to 10 C. and a further 0.38 g (9.5 mmol) sodium hydride are added. The mixture is stirred for 4 hours at 10-15 C. 100 mL ethyl acetate and 1 kg ice are added to the reaction solution. The resulting suspension is diluted with 3 L demineralised water. The suspension is stirred for 2 hours, the precipitate is suction filtered and the filter cake is washed with demineralised water. The product is dried at 50 C. in the vacuum drying cupboard. 273 g of product 9 are obtained as colourless crystals.
	With sodium hydride; In N,N-dimethyl acetamide; mineral oil; at 0 - 20℃; for 0.833333h;	25.0 g of the compound Z3d and 6.5 mL (0.1 mol) methyl iodide were placed in 250 mL dimethylacetamide and at -10 C. 3.8 g (0.95 mol) sodium hydride as a 60% dispersion in mineral oil was added. It was stirred for 20 min at 0 C., then for 30 min at ambient temperature and finally ice was added. The reaction mixture was evaporated down and combined with 300 mL water. The precipitate formed was suction filtered and washed with petroleum ether. Yield: 23.0 g of a compound Z3e (colourless solid)
	With sodium hydride; In ISOPROPYLAMIDE; at 4 - 20℃; for 7.0h;Product distribution / selectivity;	38 g (0.95 mol) sodium hydride (60% dispersion in mineral oil) are added batchwise to a solution of 264 g (0.94 mol) of 8 and 161 g (1.13 mol) methyl iodide in 2 L dimethylacetamide at 4-10 C. within one hour. The cooling bath is removed and the mixture is allowed to come up to 20 C. within 2 hours. It is cooled to 10 C. and a further 0.38 g (9.5 mmol) sodium hydride are added. The mixture is stirred for 4 hours at 10-15 C. 100 mL ethyl acetate and 1 kg ice are added to the reaction solution. The resulting suspension is diluted with 3 L demineralised water. The suspension is stirred for 2 hours, the precipitate is suction filtered and the filter cake is washed with demineralised water. The product is dried at 50 C. in the vacuum drying cupboard. 273 g of product 9 are obtained as colourless crystals.

References: [1]Angewandte Chemie - International Edition,2011,vol. 50,p. 9378 - 9381.
[2]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 764 - 769.
[3]ChemBioChem,2016,vol. 17,p. 759 - 767.
[4]Journal of Medicinal Chemistry,2019,vol. 62,p. 2618 - 2637.
[5]Patent: US2006/46989,2006,A1 .Location in patent: Page/Page column 14.
[6]Patent: WO2006/21378,2006,A1 .Location in patent: Page/Page column 37.
[7]Patent: WO2006/18182,2006,A1 .Location in patent: Page/Page column 47; 59.
[8]Patent: US2006/35903,2006,A1 .Location in patent: Page/Page column 15.
[9]Patent: US2008/177066,2008,A1 .Location in patent: Page/Page column 57; 59-60.
[10]Patent: US2004/176380,2004,A1 .Location in patent: Page/Page column 10.
[11]Patent: WO2004/76454,2004,A1 .Location in patent: Page/Page column 28.
[12]Patent: US2006/35902,2006,A1 .Location in patent: Page/Page column 6.
[13]Journal of Medicinal Chemistry,2018,vol. 61,p. 7785 - 7795.

5
[ 755039-55-5 ]
[ 2486-69-3 ]
[ 755039-56-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In ethanol; water; for 48.0h;Heating / reflux;	6.0 g of the compound Z3e and 5.1 g (31 mmol) 4-amino-3-methoxybenzoic acid are suspended in 90 mL ethanol and 350 mL water, combined with 3.5 mL concentrated hydrochloric acid and refluxed for 48 h. The reaction mixture is evaporated down, the residue stirred with methanol/diethyl ether and the precipitate formed is suction filtered. Yield: 6.3 g of a compound Z3 (light beige crystals)
	With hydrogenchloride; In ethanol; water; for 48.0h;Heating / reflux;	6.0 g of the compound Z3e and 5.1 g (31 mmol) of 4-amino-3-methoxybenzoic acid are suspended in 90 mL ethanol and 350 mL water, combined with 3.5 mL conc. hydrochloric acid and refluxed for 48 h. The reaction mixture is evaporated down, the residue is stirred with methanol/diethyl ether and the precipitate formed is suction filtered. Yield: 6.3 g of a compound Z3 (light beige crystals)
	With hydrogenchloride; In ethanol; water; for 48.0h;Heating / reflux;	6.0 g of the compound Z3e and 5.1 g (31 mmol) 4-amino-3-methoxybenzoic acid were suspended in 90 mL ethanol and 350 mL water, combined with 3.5 mL conc. hydrochloric acid and refluxed for 48 h. The reaction mixture was evaporated down, the residue stirred with methanol/diethyl ether and the precipitate formed was suction filtered. Yield: 6.3 g of a compound Z3 (light beige crystals)

References: [1]ChemBioChem,2016,vol. 17,p. 759 - 767.
[2]Angewandte Chemie - International Edition,2011,vol. 50,p. 9378 - 9381.
[3]Patent: WO2006/18182,2006,A1 .Location in patent: Page/Page column 47; 59.
[4]Patent: US2006/35903,2006,A1 .Location in patent: Page/Page column 15.
[5]Patent: US2004/176380,2004,A1 .Location in patent: Page/Page column 10.
[6]Patent: WO2004/76454,2004,A1 .Location in patent: Page/Page column 28; 29.
[7]Journal of Medicinal Chemistry,2018,vol. 61,p. 7785 - 7795.

6
[ 755039-55-5 ]
[ 100-46-9 ]
C₂₁H₂₇N₅O*ClH [ No CAS ]

References: [1]Patent: WO2005/123736,2005,A1 .Location in patent: Page/Page column 18; 22.

7
[ 755039-55-5 ]
[ 144-62-7 ]
C₂H₂O₄*C₂₁H₂₆ClN₅O [ No CAS ]

References: [1]Patent: WO2005/123736,2005,A1 .Location in patent: Page/Page column 18; 22.

8
[ 755039-55-5 ]
[ 144-62-7 ]
C₂H₂O₄*C₂₂H₂₉N₅O₂ [ No CAS ]

References: [1]Patent: WO2005/123736,2005,A1 .Location in patent: Page/Page column 18-19; 22.

9
[ 755039-54-4 ]
[ 616-38-6 ]
[ 755039-55-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dimethylcarbonate; at 130℃; for 6.0h;Autoclave;Product distribution / selectivity;	A suspension of 100 g (356 mmol) 8 and 73.8 g (534 mmol) potassium carbonate in 400 mL dimethylcarbonate is heated to 130 C. in an autoclave for 6 hours. The mixture is left to cool and 300 mL demineralised water and 200 mL ethyl acetate are added with stirring. The aqueous phase is separated off together with undissolved salts. 500 mL of solvent are distilled off from the organic phase at a pressure 180 mbar and a heating bath temperature of 70 C. 600 mL demineralised water are added to the residue and 100 mL solvent are distilled off at a pressure of 150 mbar and a heating bath temperature of 80 C. 350 mL ethanol are added to the suspension which is then heated to 65 C. The solution is left to cool and inoculated. It is cooled to 10 C., the precipitate is suction filtered and washed with a mixture of demineralised water and ethanol (2.5:1). The product is dried at 50 C. in the vacuum drying cupboard. 95.5 g product 2 are obtained.

References: [1]Patent: US2006/35902,2006,A1 .Location in patent: Page/Page column 7.

10
[ 755039-55-5 ]
[ 876126-60-2 ]
[ 755038-02-9 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In Methyl isobutyl carbinol; for 5.0h;Heating / reflux;	Preparation of the Compound of Example No. 46 by Reacting 4 with 9; A suspension of 201 g (1.06 mol) para-toluenesulphonic acid-hydrate, 209 g (706 mmol) 9 and 183 g (695 mmol) 4 in 800 mL 2-methyl-4-pentanol is refluxed. 100 mL solvent are distilled off. The mixture is refluxed for 3 hours, 200 mL of 2-methyl-4-pentanol are added and 120 mL of solvent are distilled off. After 2 hours heating at reflux temperature a further 280 mL solvent are distilled off. The mixture is cooled to 100 C. and 1 L demineralised water and then 0.5 L ethyl acetate are added to the reaction solution. The organic phase is separated off and the aqueous phase is again washed with 0.5 L ethyl acetate. 1.5 L dichloromethane and 0.5 L ethyl acetate are added to the acidic aqueous phase. The pH value of the aqueous phase is adjusted to pH 9.2 with 260 mL of 6 normal sodium hydroxide solution. The aqueous phase is separated off and the organic phase is washed three times with in each case 1 L of 1 normal aqueous sodium hydrogen carbonate solution. The organic phase is dried over sodium sulphate, filtered and the solvent is evaporated down under reduced pressure. 406 g of crude product are obtained.The crude product is dissolved in 1.5 L ethyl acetate. At a temperature of 50-55 C. 2.5 L of methyl-tert.-butylether are added. The mixture is inoculated at 45 C. and stirred for 16 hours with cooling to ambient temperature. The suspension is stirred for 3.5 hours at 0-5 C. and the precipitate is suction filtered. The filter cake is washed again with methyl-tert.-butylether/ethyl acetate (2:1) and methyl-tert.-butylether. The product is dried at 50 C. in the vacuum drying cupboard. 236 g of crystalline compound of Example no. 46 are obtained as the anhydrate (I).
		A suspension of 201 g (1.06 mol) para-toluenesulphonic acid-hydrate, 209 g (706 mmol) 9 and 183 g (695 mmol) 4 in 800 mL 2-methyl-4-pentanol is refluxed. 100 mL solvent are distilled off. The mixture is refluxed for 3 hours, 200 mL of 2-methyl-4-pentanol are added and 120 mL of solvent are distilled off. After 2 hours heating at reflux temperature a further 280 mL solvent are distilled off. The mixture is cooled to 100 C. and 1 L demineralised water and then 0.5 L ethyl acetate are added to the reaction solution. The organic phase is separated off and the aqueous phase is again washed with 0.5 L ethyl acetate. 1.5 L dichloromethane and 0.5 L ethyl acetate are added to the acidic aqueous phase. The pH value of the aqueous phase is adjusted to pH 9.2 with 260 mL of 6 normal sodium hydroxide solution. The aqueous phase is separated off and the organic phase is washed three times with in each case 1 L of 1 normal aqueous sodium hydrogen carbonate solution. The organic phase is dried over sodium sulphate, filtered and the solvent is evaporated down under reduced pressure. 406 g crude product are obtained.

References: [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 764 - 769.
[2]Patent: US2008/177066,2008,A1 .Location in patent: Page/Page column 57; 60.
[3]Patent: US2006/35902,2006,A1 .Location in patent: Page/Page column 7.

11
[ 487065-22-5 ]
[ 755039-55-5 ]
C₂₆H₃₆N₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 120℃; for 5.0h;	1.5 g Z3e and 1.22 g tert-butyl 4-amino-3-methoxy-phenyl-carbamate were melted together at 120 C. for 5 h. After cooling the reaction mixture was dissolved in dichloromethane and extracted 2× with potassium carbonate solution and 2× with water. After drying the org. phase the mixture was separated by silica gel chromatography (eluant 99:1, CH2Cl2:MeOH) and the product fractions were combined. Yield: 0.92 g of a compound Z3f (light brown crystals)

References: [1]Patent: US2006/46989,2006,A1 .Location in patent: Page/Page column 14.

12
[ 487065-22-5 ]
[ 755039-55-5 ]
C₂₆H₃₆N₆O₃ [ No CAS ]

References: [1]Patent: WO2006/21378,2006,A1 .Location in patent: Page/Page column 37.

13
[ 755039-55-5 ]
[ 367-24-8 ]
[ 1021853-59-7 ]

Yield	Reaction Conditions	Operation in experiment
20%		Stage 1 - (7R)-2-[(4-Bromo-2-fluorophenyl)amino]-8-cyclopentyl-7-ethyl-5-methyl-7,8- dihydropteridin-6(5H)-oneTo a suspension of 4-bromo-2-fluoro-phenylamine (388mg, 2.04mmol) in ethanol (2.5ml) and water (10ml) was added concentrated HCI (0.26ml) and intermediate A (300mg, 1.02mmol). The mixture was heated at 800C for 18 hours, cooled and the solvent was removed under reduced pressure. The residue was diluted with EtOAc (10ml) and washed with saturated NaHCO3 (2 x 10 ml). The organic layer was dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by column chromatography (20 - 50% EtOAc in heptane) to afford the title product as a yellow oil (90mg, 20%). ESMS: m/z 448, 449, 450 [Br splitting].

References: [1]Patent: WO2008/50078,2008,A1 .Location in patent: Page/Page column 45.

14
[ 755039-55-5 ]
[ 123-30-8 ]
[ 1021943-16-7 ]

Yield	Reaction Conditions	Operation in experiment
50%		Intermediate 2A:(y/^^delta-Cvclopentyl-T-ethyl^-rf^hvdroxyphenv?aminoi-delta-methyl-y.delta-dihvdropteridin- 6(5H)-one; The title intermediate was prepared from Intermediate 1 according to the general procedure (Scheme 1 ).To a solution of (7R)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5AV)- one [Intermediate 1] (200mg, 0.68mmol) in EtOH (2ml_), water (8ml_) and concentrated HCI (0.2ml_) was added 4-aminophenol (148mg, 1.36mmol). The reaction mixture was refluxed for 18 hours and concentrated under reduced pressure. The residue was partitioned between sat. NaHCO3 (2OmL) and a mixture of MeOH/DCM (1 :3, 2OmL). The aqueous layer was separated and extracted with MeOH/DCM (1 :3, 20 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to leave a brown solid. Trituration with Et?O afforded the titled intermediate as a grey solid (125mg, 50% yield). ESMS: m/z 368 [M+H]+ 1H NMR (DMSO-d6, 300 MHz) 8.90 (1 H, s), 8.64 (1 H, s), 7.74 (1H, s), 7.43 (2H, d, J=8.9 Hz), 6.64 (2H, d, J=8.9 Hz), 4.39- 4.29 (1 H, m), 4.16 (1H, dd, J=3.6, 7.8 Hz), 3.22 (3H, s), 1.99-1.54 (10H, m), 0.77 (3H, t, J=7.4 Hz). EPO <DP n="24"/;

References: [1]Patent: WO2008/50096,2008,A1 .Location in patent: Page/Page column 22.

15
[ 755039-55-5 ]
[ 1021943-27-0 ]
[ 1021943-49-6 ]

Yield	Reaction Conditions	Operation in experiment
43%	In 2-ethoxy-ethanol; at 150℃; for 4.0h;	Stage 1; - Cyclopentyl lambda/-(terf-butoxycarbonyl)-4-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6- oxo-5,6,7.8-tetrahydropteridin-2-yl]amino}-L-phenylalaninateTo a solution of (7f?)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5/-/)- one [Intermediate 1] (100mg, 0.34mmol) in 2-ethoxyethanol (2mL) was added cyclopentyl 4-amino-lambda/-(terf-butoxycarbonyl)-L-phenylalaninate [Intermediate 6A] (170mg, 0.51 mmol). The reaction mixture was heated at 150C for 4 hours, cooled and concentrated under reduced pressure to give a brown residue. The residue was purified by column chromatography (5% methanol / 1% NH4OH in EtOAc) to afford the product as a yellow solid (89mg, 43% yield). ESMS: m/z 607 [M+H]+

References: [1]Patent: WO2008/50096,2008,A1 .Location in patent: Page/Page column 51.

16
[ 755039-55-5 ]
[ 1034618-02-4 ]
[ 1159994-47-4 ]

Yield	Reaction Conditions	Operation in experiment
22%		To a suspension of (R)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydro-5H- pteridin-6-one (0.60 g, 2 mmol), prepared as described in WO 2004/076454, in a 2/1 mixture E^O/Ethanol (60 mL), were added 37%HC1 (0.6 mL) and 2-trifluoromethoxy-5-(4-Methyl-piperazin-l-yl)-phenylamine (0.55 g, 2 mmol), prepared as described inPreparation 1. The reaction was refluxed for 72 hours, concentrated to small volume(20 mL) diluted with water (30 mL) and extracted with DCM (2 X 50 mL). The aqueous phase was neutralized by addition of NaHCCh then extracted with DCM (2 X 50 mL).The organic fractions were combined, dried over sodium sulfate and solvent was evaporated to drieness. Purification of crude solid by flash chromatography on silica gel <n="22"/>(eluant: DCM/EtOH 90/10) yield the title compound as an light brown solid (0.23 g ,22% yield).1H NMR (400 MHz, DMSO-J6) delta ppm 0.76 (t, J=7.50 Hz, 3 H) 1.44 (m, 2H) 1.60 (m,2H) 1.73 (m, 2H) 1.82 (m, 4H) 2.27 (s, 3 H) 2.49 - 2.53 (m, 4 H) 3.09 - 3.18 (m, 4 H) 3.23 (s, 3 H) 4.18 (dd, J=7.56, 3.66 Hz, 1 H) 4.20 - 4.28 (m, 1 H) 6.67 (dd, J=9.15, 3.05Hz, 1 H) 7.12 - 7.21 (m, 1 H) 7.54 (d, J=3.05 Hz, 1 H) 7.77 (s, 1 H) 7.93 (s, 1 H); MS(ESI): 534 [M+H]+.

References: [1]Patent: WO2009/71480,2009,A2 .Location in patent: Page/Page column 20-21.

17
[ 755039-55-5 ]
[ 201230-82-2 ]
[ 1313519-03-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; tert-butyl alcohol;1,3-bis-(diphenylphosphino)propane; palladium diacetate; In dimethyl sulfoxide; at 80℃; under 7600.51 Torr; for 10.0h;	Intermediate B (10.0 g, 34.01 mmol) was dissolved in 15 mL of DMSO and 185 mL of tBuOH and Pd(OAc)2 (1.14 g, 5.1 mmol), DPPP (2.2 g, 5.1 mmol) and TEA (7.7 g, 76.5 mmol) were added. The solution was stirred at 80 C for 10 h under CO (10 atm). The solvent was removed under reduced pressure and the residue was dissolved in EtOAc. The organic layer was washed with water and brine, dried with Na2S04, purified by silica gel column (DCM:MeOH = 20: 1) to give (R)-8- cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridine-2-carboxylic acid (compound 1-245, 2.2 g) as a yellow solid.

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 152; 153.

18
[ 504-24-5 ]
[ 755039-55-5 ]
[ 1313518-59-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In 1,4-dioxane; isopropyl alcohol; at 160℃; for 1.0h;microwave irradiation;	To a solution of the Intermediate B (400 mg, 1.36 mmol) in 5 mL of isopropanol in a microwave vial, 4N HCI in dioxane (0.43 mL) and 4-aminopyridine (320 mg, 2 eq) were added and the vial was heated in a microwave oven at 160 C for 1 hour. Solvent was removed under reduced pressure and the resulting yellow solid was purified by reversed phase HPLC to give the title compound. XH NMR (CDCI3) delta: 9.62 (bs, IH), 8.91 (d, J = 7.7 Hz, 2H), 7.81 (s, IH), 7.37 (d, J = 7.8 Hz, 2H), 4.44- 4.36 (m, 2H), 3.41 (s, 3H), 2.08-1.71 (m, 10H), 0.89 (t, J = 7.5 Hz, 3H).

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 131.

19
[ 755039-55-5 ]
[ 5188-07-8 ]
[ 1313519-18-4 ]

Yield	Reaction Conditions	Operation in experiment
	In ISOPROPYLAMIDE; at 150℃; for 2.0h;	To a stirring mixture of Intermediate B (600 mg, 1 eq) in 2.1 mL of DMA, sodium methanethiolate (286 mg, 2.0 eq) was added. The reaction mixture was placed in a 150 C preheated oil bath and stirred for 2 hr. The reaction mixture was cooled to rt and slowly diluted with ethyl ether and brine. The layers were separated. The aqueous layer was extracted with ethyl ether (2 x 30 mL). The combined organic layers were dried over MgS04, filtered, and concentrated under reduced pressure. To a stirring mixture of the crude methyl sulfide pteridine in 5 mL of HOAc at 0 C, a solution of KMn04 (643 mg, 2 eq) in 5 mL of water was added slowly over 10 min. The reaction mixture was reacted for 1 h before additional KMn04 (320 mg, 0.5 eq) in water was added. Cold water and a 10% a2S203 solution were added. The reaction mixture was diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (2 x 25 mL). The combined organic layers were dried over MgS04, filtered, and concentrated under reduced pressure. The resulting material was purified by MPLC to give compound 1-306. LCMS: 339.1 m/z (M+H)+.

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 159.

20
[ 670-96-2 ]
[ 755039-55-5 ]
[ 1313518-37-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; In 1,2-dimethoxyethane; at 200℃; for 2.0h;microwave irradiation;	A mixture of intermediate B (50 mg, 0.17 mmol), 2-phenyl-lH-imidazole (3.4 mmol, 20 equivalents, 490 mg), Cul (0.05 equivalents, 0.009 mmol, 1.7 mg), trans- l,2-bis(methylamino)cyclohexane (14.2 mg, 0.003 mL) and K2CO3 (1.7 mmol, 233 mg) in 2 mL of DME were heated in a microwave at 200 C for 2h. The reaction was diluted with DME, filtered through Celite and evaporated. The residue was purified by reverse phase HPLC using a gradient of 30-50% CH3CN (0.1% TFA) over 30 min with a flow rate of 20 mL/min eluting from a PCRP-5 column (2.5 x 30 cm). Following lyophylization, 22.8 mg of the title compound was obtained with a purity > 99%. ¾ NMR (CDCI3) delta: 7.9-7.3 (m, 8H), 4.2 (m, 1H), 3.55 (m, 1H), 3.3 (s, 3H), 2.0-1.1 (m, 10H) and 0.85 ppm (t, 3H); LCMS: 403.2 m/z (M+H)+; ret. Time: 3.77 min (Analytical Method A).

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 119.

21
[ 755039-55-5 ]
[ 18502-05-1 ]
[ 1313518-38-5 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; In N,N-dimethyl-formamide; at 110℃; for 18.0h;Inert atmosphere; sealed vial;	A mixture of intermediate B (150 mg, 0.509 mmol), 2-(lH-imidazol-4- yl)acetonitrile (1.01 mmol, 2 equivalents, 108 mg), Cul (0.1 equivalents, 0.0509 mmol, 10 mg), trans-1,2 bis(methylamino)cyclohexane (14 mg, 0.102 mmol) and CS2CO3 (1.01 mmol, 331 mg) in DMF (1 mL) was purged with nitrogen and was subsequently heated in a sealed vial at 110 C for 18 h. The reaction was diluted with ethyl acetate, filtered through Celite and evaporated. The residue was purified by reverse phase preparative HPLC and lyophilized to give the title compound (185 mg). ^ MR CDCls) delta: 8.66 (s, 1H), 7.91 (s, 1H), 7.76 (s, 1H), 4.31-4.37 (m, 2H), 3.91 (s, 2H), 3.38 (s, 3H), 1.70-2.13 (m, 10H), and 0.93 ppm (t, J= 7.4 Hz, 3H); LCMS: 366.1 m/z (M+H)+; ret. Time: 3.444 min (Analytical Method A).

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 120.

22
[ 755039-55-5 ]
[ 18502-05-1 ]
[ 1313518-55-6 ]

References: [1]Patent: WO2011/79114,2011,A1 .

23
[ 755039-55-5 ]
[ 536-74-3 ]
[ 1313518-82-9 ]

References: [1]Patent: WO2011/79114,2011,A1 .

24
[ 755039-55-5 ]
[ 536-74-3 ]
[ 1313518-83-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; for 18.0h;Inert atmosphere; Reflux;	To a solution of Intermediate B (1.0 eq) in DMF, ethynylbenzene (compound III-139, 3.0 eq), Pd(PPh3)2Cl2 (0.2 eq), Cul (0.25 eq) and Et3N (5.0 eq) were added. The mixture was refluxed for 18 h under argon, extracted with EtOAc and purified by silica gel column to give (R)-8-cyclopentyl-7-ethyl-5-methyl-2- (phenylethynyl)-7,8-dihydropteridin-6(5H)-one (compound IV- 139).

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 142; 143.

25
[ 755039-55-5 ]
[ 98-86-2 ]
[ 1313516-81-2 ]

Yield	Reaction Conditions	Operation in experiment
19%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In water; toluene; at 120℃; for 60.0h;Inert atmosphere;	5.0 g of Intermediate B, 2.5 eq of acetophenone, 0.05 eq of Pd2(dba)3, 0.1 eq of BINAP and 2.0 eq of CS2CO3 were suspended in a mixture of 50 mL toluene and 10 mL of water, then heated to 120 C under 2 for 60 hours. After cooling to rt, added 100 mL of water and washed the organic phase, dried with anhydrous a2S04, concentrated and purified by silica gel column (PE:EA=3: 1) to give the pureIntermediate B-l (1.2 g, 19 %) as yellow solid.

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 55.

26
[ 755039-55-5 ]
[ 1692-15-5 ]
[ 1313518-30-7 ]

Yield	Reaction Conditions	Operation in experiment
64%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 120℃; for 0.666667h;microwave irradiation;	To a solution of 150 mg of intermediate B in DME (5 mL) and water (4: 1) Pd(dppf)Ci2 (75 mg), a2C03 (162 mg), and pyridin-4-ylboronic acid (90 mg) were added. The reaction mixture was heated in a microwave at 120 C for 40 min. The mixture was concentrated and extracted with EtOAc and dried with a2S04. The solvent was removed and the residue was purified by silica column to give the title compound (107 mg, yield 64%). LCMS (0.05%TFA): 338.0 m/z (M+H)+; XH-NMR (CDCI3, 400MHz): delta: 8.72 (d, 2H, J=3.6 Hz), 8.17 (d, 2H, J=3.6Hz), 7.80 (s, 1H), 4.46 (m, 1H), 4.32 (m, 1H), 3.40 (s, 3H), 2.17 (m, 1H), 2.06 (m, 1H), 1.99(m, 1H), 1.92 (m, 4H), 1.70-1.76 (m, 3H), 0.88 (t, 3H, J=6Hz).

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 115.
[2]ChemMedChem,2013,vol. 8,p. 1295 - 1313.

27
[ 755039-55-5 ]
[ 1692-15-5 ]
[ 1313518-32-9 ]

References: [1]Patent: WO2011/79114,2011,A1 .

28
[ 755039-55-5 ]
[ 401815-98-3 ]
[ 1313518-34-1 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 140℃; for 0.666667h;microwave irradiation;	To a solution of intermediate B (300 mg, 1.2 mmol) in 6 mL of DME and 2 mL of water, 2-(fluoro)pyridin-4-ylboronic acid (719 mg, 5.1 mmol), Pd(dppf)Ci2 (160 mg, 0.13 mmol), and 2M a2C03 (324 mg, 3.06 mL) were added. The mixture was microwave heated at 140 C for about 40 min. The mixture was concentrated under reduced pressure and extracted with EtOAc. The combined organic phase was 8576.98-304 dried with Na2S04 and concentrated under reduced pressure. The crude material was purified by silica gel flash column chromatography (PE: EA=75%) to give the title compound as a white solid (200 mg, 65% yield).

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 117; 118.

29
[ 512-56-1 ]
[ 755039-54-4 ]
[ 755039-55-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; In 1,4-dioxane; at 90℃; for 6.0h;Inert atmosphere;	Compound IV (260 mg, 0.93 mmol) was dissolved in dioxane (5 ml).Trimethylphosphate (650 mg, 4.6 mmol) and K2CO3 (192 mg, 1.39 mmol) were added, and the reaction mixture was stirred under 2 at 90 C for 6hr until the starting material was consumed. The reaction mixture was diluted with water and extracted with EtOAc. The solvent was removed, and the residue was purified by silica gel column chromatography (PE: EtOAc=l : l) to give intermediate B as a white solid (270 mg, 86 %). ¾ NMR (CDCI3) delta: 7.7 (s, 1H), 4.34 (m, 1H), 4.25 (m, 1H), 3.33 (s, 3H), 2.1-1.6 (m, 10H) and 0.86 ppm (t, 3H).

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 54; 55.

30
[ 755039-55-5 ]
[ 1313516-82-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine; In ethanol; at 120℃; for 1.0h;microwave irradiation;	Intermediate B and hydrazine (6 equivalents) in ethanol was heated in a microwave for 1 h at 120 C. The solvent was removed to give Intermediate B-2. This material was used without further purification.

References: [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 55.

31
[ 755039-55-5 ]
[ 1313518-33-0 ]

References: [1]Patent: WO2011/79114,2011,A1 .

32
[ 755039-55-5 ]
[ 1313518-35-2 ]

References: [1]Patent: WO2011/79114,2011,A1 .

33
[ 755039-55-5 ]
[ 1313518-74-9 ]

References: [1]Patent: WO2011/79114,2011,A1 .

34
[ 755039-55-5 ]
[ 1313518-75-0 ]

References: [1]Patent: WO2011/79114,2011,A1 .

35
[ 755039-55-5 ]
[ 1313518-76-1 ]

References: [1]Patent: WO2011/79114,2011,A1 .

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Chan-Lam Coupling Reaction • Complex Metal Hydride Reductions • General Reactivity • Grignard Reaction • Halogenation • Heat of Combustion • Hiyama Cross-Coupling Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

Related Functional Groups of
[ 755039-55-5 ]

Chlorides

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2-Chloro-9-methyl-7H-purin-8(9H)-one

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Amides

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(R)-2-Chloro-7-ethyl-8-isopropyl-5-methyl-7,8-dihydropteridin-6(5H)-one

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Related Parent Nucleus of
[ 755039-55-5 ]

Other Aromatic Heterocycles

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(R)-2-Chloro-7-ethyl-8-isopropyl-5-methyl-7,8-dihydropteridin-6(5H)-one

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P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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CAS No.: 755039-55-5

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CAS No.: 755039-55-5

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[ 755039-55-5 ]

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{[proInfo.proName]}

CAS No.: 755039-55-5

{[proInfo.proName]}

CAS No.: 755039-55-5

Alternative Products

Product Details of [ 755039-55-5 ]

Safety of [ 755039-55-5 ]

Computational Chemistry of [ 755039-55-5 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 755039-55-5 ]

[ 755039-55-5 ] Synthesis Path-Downstream 1~35

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 755039-55-5 ]

Chlorides

Amides

Related Parent Nucleus of [ 755039-55-5 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 755039-55-5 ]

Related Parent Nucleus of
[ 755039-55-5 ]