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Chemical Structure| 2164-67-2 Chemical Structure| 2164-67-2

Structure of 2164-67-2

Chemical Structure| 2164-67-2

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Product Details of [ 2164-67-2 ]

CAS No. :2164-67-2
Formula : C5H7N3O
M.W : 125.13
SMILES Code : OCC1=NC(N)=NC=C1
MDL No. :MFCD01689391
InChI Key :TWYCDZQLLFNFGK-UHFFFAOYSA-N
Pubchem ID :200493

Safety of [ 2164-67-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 2164-67-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 32.56
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

72.03 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.82
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-1.0
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-0.59
Log Po/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.

-1.16
Log Po/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

0.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.38

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-0.41
Solubility 48.3 mg/ml ; 0.386 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.

-0.03
Solubility 118.0 mg/ml ; 0.942 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

-1.08
Solubility 10.4 mg/ml ; 0.0832 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.

-7.77 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)

1.59

Application In Synthesis of [ 2164-67-2 ]

* 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 [ 2164-67-2 ]

[ 2164-67-2 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 402925-20-6 ]
  • [ 2164-67-2 ]
  • 4-phthalimidomethyl-benzenesulfonic acid-(4-hydroxymethyl-pyrimidin-2-ylamide) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With methanol; sodium tetrahydroborate; at 0 - 20℃; for 2h; General procedure: To a solution of aldehyde in the indicated solvent is added sodium borohydride at 0 °C. After stirring at room temperature for 2 hours, water is added and the mixture is concentrated.Following Procedure C using crude 4 (1.0 g, 6.35 mmol), MeOH, and sodium borohy dride (360 mg, 9.55 mmol), then quench with water (1 mL) and purify with silica gel column chromatography (MeOH:DCM := 1 :50) to give AS as a solid (650 mg, 65percent yield). (MS: [M+H]+ 160.1)
  • 4
  • [ 2164-66-1 ]
  • [ 2164-67-2 ]
YieldReaction ConditionsOperation in experiment
73% <strong>[2164-66-1]2-Amino-4-methoxycarbonylpyrimidine</strong> (3.0g, 20mmol, Reference Compound No.3-1) was suspended in a mixture solvent of ethanol (150mL) and dichloromethane (20mL), then sodium borohydride (2.2g, 59mmol) was added thereto at room temperature, and the whole was stirred for 24 hours. Acetone (20mL) was added gradually under ice-cooling, and then 2M hydrochloric acid was added until the bubbles were no longer formed. Saturated aqueous sodium hydrogencarbonate solution was added to adjust the pH of the reaction mixture to 8, and the precipitated solid was filtered out. The filtrate was concentrated under reduced pressure, then suspended in a 10percent methanol-chloroform solution, and the mixture was filtered again with silica gel (5.0g). The filtrate was evaporated under reduced pressure, the precipitated solid was filterd off with ethyl acetate, and dried under reduced pressure to give 1.8g of the title Reference Compound as a pale yellow solid (Yield: 73percent) 1H-NMR (400MHz, DMSO-d6) delta 4.30(s,2H),5.35(s,1H),6.48(s,2H),6.65(d,J = 4.9 Hz,1H),8.19(d,J = 4.9 Hz,1H)
  • 5
  • [ 18162-48-6 ]
  • [ 2164-67-2 ]
  • [ 912470-40-7 ]
YieldReaction ConditionsOperation in experiment
84% 2-Amino-4-hydroxymethylpyrimidine (750mg,6.0mmol,Reference Compound No.4-1) and tert-butyldimethylsilyl chloride (990mg, 6.6mmol) were suspended in anhydrous N,N-dimethylformamide (8.0mL), then imidazole (0.90g, 13mmol) was added thereto and the mixture was stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (50mL), washed twice with saturated aqueous sodium hydrogencarbonate solution (50mL), and then washed with brine (50mL), and dried over anhydrous magnesium sulfate. Then the solvent was evaporated under reduced pressure, the precipitated solid was filtered off with 50percent ethyl acetate-n-hexane solution, and dried under reduced pressure to give 1.2g of the title Reference Compound as a white solid (Yield: 84percent). 1H-NMR(400MHz,CDCl3) delta 0.11(s,6H),0.95(s,9H),4.59(s,2H),5.03(s,2H),6.87(d,J = 5.1 Hz,1H),8.29(d,J = 5.1 Hz,1H)
  • 6
  • [ 124-63-0 ]
  • [ 2164-67-2 ]
  • [ 912470-43-0 ]
YieldReaction ConditionsOperation in experiment
53% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 20℃; for 7h; N,N-Diisopropylethylamine(490muL,2.9mmol) and methanesulfonyl chloride(110muL,1.5mmol) were added to a suspension of <strong>[2164-67-2]2-amino-4-hydroxymethylpyrimidine</strong> (170mg,1.3mmol, Reference Compound No.4-1) in anhydrous tetrahydrofuran (5.0 mL) under ice-cooling, and the mixture was stirred for 7 hours at room temperature. The reaction mixture was diluted with ethyl acetate (300mL), washed with water (300mL), and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the precipitated solid was filtered off with ethyl acetate, and dried under reduced pressure to give 140mg of the title Reference Compound as a white solid (Yield: 53percent). 1H-NMR(500MHz, DMSO-d6) delta 3.30(s,3H),5.06(s,2H),6.63(d,J = 5.2 Hz,1H),6.78(s,2H),8.28(d,J = 5.2 Hz, 1H)
  • 7
  • [ 165807-05-6 ]
  • [ 1220627-33-7 ]
  • [ 2164-67-2 ]
YieldReaction ConditionsOperation in experiment
7% With hydrogenchloride; sodium tetrahydroborate; NaOH; In tetrahydrofuran; methanol; water; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; Intermediate P: 1-(4-((2-Aminopyrimidin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureaHydrochloric acid (2M, 207 mL, 414 mmol) was added to 4-(dimethoxymethyl)pyrimidin-2-amine (68) (WO 2007/096764) (14.0 g, 83 mmol) and the mixture heated at 48° C. for 16 hr.The mixture was cooled to RT and was neutralized with solid Na2CO3 which produced a precipitate at pH 7.The suspension was diluted with EtOAc (300 mL) and the solid removed by filtration.The organic layer was separated and the aqueous layer was extracted with 1percent MeOH in THF (4*300 mL).The organics were combined, dried and then evaporated in vacuo.The residue (ca. 4.0 g) was suspended in a mixture of MeOH (100 mL), THF (100 mL) and water (100 mL) and treated with NaBH4 (1.57 g, 41.4 mmol).After stirring for 1 hr a solution of NaOH (1M, 20 mL) was added and the mixture was allowed to stand at RT for 48 hr.The solvents were evaporated to give a yellow solid which was partitioned between water (50 mL) and EtOAc (100 mL).The solid which formed at the interface was removed by filtration and the aq layer was extracted with THF (3*300 mL) then dried and evaporated to give a yellow solid.The material was suspended in THF (100 mL) and MeOH (50 mL) and absorbed onto silica gel (20 g) and subjected to column chromatography (80 g, 15percent MeOH in DCM isocratic elution) to give (2-aminopyrimidin-4-yl)methanol (69) as an off-white solid (720 mg, 7percent): m/z 126 (M+H)+ (ES+).
  • 8
  • [ 605-62-9 ]
  • [ 2164-67-2 ]
  • [ 1220627-31-5 ]
YieldReaction ConditionsOperation in experiment
93% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at -50 - 20℃; for 1.08333h; To a stirred mixture of (69) (700 mg, 3.92 mmol), 4-nitronaphthol (2) (741 mg, 3.92 mmol) and PPh3 (1.23 g, 4.70 mmol) in THF (20 mL) under nitrogen at ?50° C. was added DIAD (996 muL, 4.70 mmol) dropwise over 5 min. The mixture was allowed to warm to RT and stirred for 1 hr during which time a yellow precipitate formed. The suspension was stirred overnight and the volatiles were evaporated in vacuo. The residue was triturated from MeOH (50 mL) and the pale yellow solid collected by filtration and washed with diethyl ether (50 mL) to give 4-((4-nitronaphthalen-1-yloxy)methyl)pyrimidin-2-amine (70) (1.10 g, 93percent): m/z 297 (M+H)+ (ES+).
With DIAD; triphenylphosphine; In tetrahydrofuran; methanol; To a stirred mixture of (69) (700 mg, 3.92 mmol), 4-nitronaphthol (2) (741 mg, 3.92 mmol) and PPh3 (1.23 g, 4.70 mmol) in THF (20 mL) under nitrogen at -50° C. was added DIAD (996 muL, 4.70 mmol) dropwise over 5 min.The mixture was allowed to warm to RT and stirred for 1 hr during which time a yellow precipitate formed.The suspension was stirred overnight and the volatiles were evaporated in vacuo.The residue was triturated from MeOH (50 mL) and the pale yellow solid collected by filtration and washed with diethyl ether (50 mL) to give 4-((4-nitronaphthalen-1-yloxy)methyl)pyrimidin-2-amine (70) (1.10 g, 93percent): m/z 297 (M+H)+ (ES+).
  • 9
  • [ 2164-67-2 ]
  • [ 1220627-32-6 ]
  • 10
  • [ 2164-67-2 ]
  • [ 1229649-45-9 ]
  • 11
  • [ 165807-06-7 ]
  • [ 2164-67-2 ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; potassium carbonate; at 0 - 5℃; for 0.5h;pH 8.0; The solution of 5.01 g 4-(dimethoxymethyl)pyrimidin-2-amine (29.5 mmol) in 100 mL 2Naq. HCI was stirred at 60°C for 5h. Reaction mixture was cooled to 0°C, then 7.60 g NaOH(190 mmol) was added portionwise. The pH was adjusted to 8 using 10percent K2C03 solution, then 2.24 g sodium borohydride (59.0 mmol) was added portionwise keeping the temperature under 5°C and stirred for 30 mm at 0°C. The reaction mixture was extracted with EtOAc, the combined organic phases were dried over Na2SO4 and concentrated underreduced pressure. The crude product was purified via flash chromatography (MeOH - containing I percentN113- and DCM).?FT NMR (400 MHz, DMSO-d5): 8,20 (d, 111), 6.66 (d, 111), 6.49 (br s, 211), 5.35 (t, IH), 4.30 (d, 211).
  • 12
  • [ 165807-05-6 ]
  • [ 2164-67-2 ]
YieldReaction ConditionsOperation in experiment
7% Hydrochloric acid (2M, 207 mL, 414 mmol) was added to 4-(dimethoxymethyl)pyrimidin-2-amine (68) (WO 2007/096764) (14.0 g, 83 mmol) and the mixture heated at 48° C. for 16 hr. The mixture was cooled to RT and was neutralized with solid Na2CO3 which produced a precipitate at pH 7. The suspension was diluted with EtOAc (300 mL) and the solid removed by filtration. The organic layer was separated and the aqueous layer was extracted with 1percent MeOH in THF (4×300 mL). The organics were combined, dried and then evaporated in vacuo. The residue (ca. 4.0 g) was suspended in a mixture of MeOH (100 mL), THF (100 mL) and water (100 mL) and treated with NaBH4 (1.57 g, 41.4 mmol). After stirring for 1 hr a solution of NaOH (1M, 20 mL) was added and the mixture was allowed to stand at RT for 48 hr. The solvents were evaporated to give a yellow solid which was partitioned between water (50 mL) and EtOAc (100 mL). The solid which formed at the interface was removed by filtration and the aq layer was extracted with THF (3×300 mL) then dried and evaporated to give a yellow solid. The material was suspended in THF (100 mL) and MeOH (50 mL) and absorbed onto silica gel (20 g) and subjected to column chromatography (80 g, 15percent MeOH in DCM isocratic elution) to give (2-aminopyrimidin-4-yl)methanol (69) as an off-white solid (720 mg, 7percent): m/z 126 (M+H)+ (ES+).
  • 13
  • [ 2164-67-2 ]
  • [ 1220627-33-7 ]
  • 14
  • [ 2164-67-2 ]
  • [ 1220627-04-2 ]
  • 15
  • [ 62671-89-0 ]
  • [ 403-33-8 ]
  • [ 2164-67-2 ]
  • C19H18FN7 [ No CAS ]
  • 16
  • [ 62671-89-0 ]
  • [ 403-33-8 ]
  • [ 2164-67-2 ]
  • C18H14FN5OS [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 2164-67-2 ]

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