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Chemical Structure| 1289387-30-9 Chemical Structure| 1289387-30-9

Structure of 1289387-30-9

Chemical Structure| 1289387-30-9

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Product Details of [ 1289387-30-9 ]

CAS No. :1289387-30-9
Formula : C6H7ClN2O
M.W : 158.59
SMILES Code : COCC1=NC(Cl)=NC=C1
English Name :2-Chloro-4-(methoxymethyl)pyrimidine
MDL No. :MFCD18837162
InChI Key :LKOWHMGUHBHEDI-UHFFFAOYSA-N
Pubchem ID :53385539

Safety of [ 1289387-30-9 ]

Computational Chemistry of [ 1289387-30-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 37.9
TPSA ?

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

35.01 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.9
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

0.85
Log Po/w (WLOGP)?

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

1.12
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.

0.01
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

1.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.14

Water Solubility

Log S (ESOL):?

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

-1.67
Solubility 3.38 mg/ml ; 0.0213 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.

-1.17
Solubility 10.8 mg/ml ; 0.0678 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

-2.79
Solubility 0.258 mg/ml ; 0.00163 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

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.

-6.66 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)

1.94

Application In Synthesis of [ 1289387-30-9 ]

* 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 [ 1289387-30-9 ]

[ 1289387-30-9 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 1289387-30-9 ]
  • [ 2892572-09-5 ]
  • [ 2892571-65-0 ]
YieldReaction ConditionsOperation in experiment
43 % Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; 3 5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazole- 4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (3) 1n (350mg, 0.94mmol) was dissolved in N,N-dimethylacetamide (20mL), 60% sodium hydride (180mg, 7.52mmol) was added under ice-cooling, reacted for 30 minutes, and 2-chloro-4-( Methoxymethyl)pyrimidine (179 mg, 1.13 mmol).React at room temperature for 30 minutes.Dilute with water (10 mL), adjust the pH to 4-5 with 1M hydrochloric acid, and extract with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse phase C18 column chromatography (acetonitrile/water) and then lyophilized to obtain the title compound 3 (200 mg, yield 43 %).
43 % Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; 1.13 Step 13: (1S, 3aS, 5S, 6aR)-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (1) 1n (350 mg, 0.94 mmol) was dissolved in N,N-dimethylacetamide (20 mL),60% sodium hydride (180 mg, 7.52 mmol) was added under ice bath,reacted for 30 minutes,2-chloro-4-(methoxymethyl)pyrimidine (179 mg, 1.13 mmol) was added,reacted at room temperature for 30 minutes.Diluted with water (10 mL),adjusted pH to 4-5 with 1M hydrochloric acid,extracted with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product. The crude product was purified by reverse phase flash column chromatography (acetonitrile/water) and then freeze-dried to obtain compound 1 (200 mg, yield 43%).
43 % Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; 1.13 Step 13: (1S, 3aS, 5S, 6aR)-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (1) 1n (350 mg, 0.94 mmol) was dissolved in N,N-dimethylacetamide (20 mL),60% sodium hydride (180 mg, 7.52 mmol) was added under ice bath,reacted for 30 minutes,2-chloro-4-(methoxymethyl)pyrimidine (179 mg, 1.13 mmol) was added,reacted at room temperature for 30 minutes.Diluted with water (10 mL),adjusted pH to 4-5 with 1M hydrochloric acid,extracted with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product. The crude product was purified by reverse phase flash column chromatography (acetonitrile/water) and then freeze-dried to obtain compound 1 (200 mg, yield 43%).
  • 2
  • [ 1289387-30-9 ]
  • [ 2892572-21-1 ]
  • [ 2892571-67-2 ]
YieldReaction ConditionsOperation in experiment
47 % Stage #1: 1-fluoro-5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridine-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; 5.6 1-Fluoro-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2 ,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (5) Dissolve 5e (130mg, 0.33mmol) in N,N-dimethylacetamide (10mL), add 60% sodium hydride (107mg, 2.66mmol) under ice-cooling, react for 30 minutes, add 2-chloro-4-( Methoxymethyl)pyrimidine (106mg, 0.67mmol), react at room temperature for 30 minutes.Dilute with water (10 mL), adjust the pH to 4-5 with 1M hydrochloric acid, and extract with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse-phase flash column chromatography (acetonitrile/water) to obtain compound 5 (80 mg, yield 47%) .
  • 3
  • [ 1289387-30-9 ]
  • [ 2892572-28-8 ]
  • [ 2892571-73-0 ]
YieldReaction ConditionsOperation in experiment
22 % Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)-1-methyloctahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; 14.6 5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-tri Azol-4-yl)-2-methylpyridin-3-yl)oxy)-1-methyloctahydropentalene-1-carboxylic acid (14) Dissolve 14e (130mg, 0.33mmol) in N,N-dimethylacetamide (10mL), add 60% sodium hydride (108mg, 2.69mmol) under ice-cooling, react for 30 minutes, add 2-chloro-4- (Methoxymethyl)pyrimidine (107mg, 0.67mmol), stirred at room temperature for 30 minutes.Add water (10 mL), adjust the pH to 5-6 with 1M hydrochloric acid, and extract with ethyl acetate (20 mL×3).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse-phase flash column chromatography (acetonitrile/water) and then lyophilized to obtain the title product 14 (38 mg, yield rate 22%).
  • 4
  • [ 2118305-70-5 ]
  • [ 1289387-30-9 ]
  • [ 2118303-43-6 ]
YieldReaction ConditionsOperation in experiment
Stage #1: (1-(3-(difluoromethoxy)-4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methanol With sodium hydride In tetrahydrofuran; mineral oil Inert atmosphere; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In tetrahydrofuran; mineral oil at 20℃;
  • 5
  • [ 18592-13-7 ]
  • [ 1289387-30-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: methanol / 3 h / Reflux 2: phosphorus pentachloride / 5,5-dimethyl-1,3-cyclohexadiene / 9 h / 70 - 90 °C 3: hydrogenchloride; chloro-trimethyl-silane; zinc / methanol / 16 h / 70 - 75 °C
  • 6
  • [ 124461-06-9 ]
  • [ 1289387-30-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: phosphorus pentachloride / 5,5-dimethyl-1,3-cyclohexadiene / 9 h / 70 - 90 °C 2: hydrogenchloride; chloro-trimethyl-silane; zinc / methanol / 16 h / 70 - 75 °C
  • 7
  • [ 1037543-27-3 ]
  • [ 1289387-30-9 ]
YieldReaction ConditionsOperation in experiment
78 % With hydrogenchloride; chloro-trimethyl-silane; zinc In methanol at 70 - 75℃; 1.3; 2.3 third step: Add intermediate 3 (1eq), zinc powder (4eq), trimethylchlorosilane (1eq) and hydrochloric acid (2eq) into methanol (10V), stir and react at 70-75°C for 16 hours, filter after cooling down, methanol /water beating to obtain 2-chloro-4-(methoxymethyl)pyrimidine (yield 78%).
  • 8
  • [ 1289387-30-9 ]
  • [ CAS Unavailable ]
  • [ 2892571-76-3 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide; mineral oil Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide; mineral oil at 20℃; Stage #3: With ammonium hydroxide In ethanol 1.13 Step 13: (1S, 3aS, 5S, 6aR)-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (1o-P1) 1n (350 mg, 0.94 mmol) was dissolved in N,N-dimethylacetamide (20 mL), 60% sodium hydride (180 mg, 7.52 mmol) was added under ice bath, reacted for 30 minutes, 2-chloro-4-(methoxymethyl)pyrimidine (179 mg, 1.13 mmol) was added, and reacted at room temperature for 30 minutes. After the reaction was completed, water (10 mL) was added for dilution, 1 M hydrochloric acid was used to adjust the pH value to 4-5, and ethyl acetate was used for extraction (20 mL × 2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse phase flash column chromatography (acetonitrile/water) and freeze-dried to obtain compound 1o (200 mg, yield 43%).
  • 9
  • [ 1289387-30-9 ]
  • [ 127958-17-2 ]
YieldReaction ConditionsOperation in experiment
68.6% With ammonia In methanol at 100℃; for 1h; Sealed tube; 1.136 Example 1.136. Synthesis of 4-(methoxymethyl)pyrimidin-2-amine A solution of 2-chloro-4-(methoxymethyl)pyrimidine (200 mg, 1.26 mmol) in a solution of NH3in MeOH (2 mL) was heated at 100 °C for 1 h in a sealed tube. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL× 2), dried over Na2SO4, filtered and concentrated to give 4-(methoxymethyl)pyrimidin-2-amine (120 mg, 68.6 %) as a white solid. LCMS m/z = 140.09 [M+H]+;1HNMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 5.0 Hz, 1H), 6.56 (d, J = 4.2 Hz, 3H), 4.24 (s, 2H), 3.34 (s, 3H).
 

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