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Structure of 180869-38-9

Chemical Structure| 180869-38-9

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Product Details of [ 180869-38-9 ]

CAS No. :180869-38-9
Formula : C8H13N3O2
M.W : 183.21
SMILES Code : CNC1=NC=CC(C(OC)OC)=N1
MDL No. :MFCD10566061
InChI Key :GVTZVNRRGNBOJF-UHFFFAOYSA-N
Pubchem ID :17840014

Safety of [ 180869-38-9 ]

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

Computational Chemistry of [ 180869-38-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 48.09
TPSA ?

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

56.27 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.09
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

0.19
Log Po/w (WLOGP)?

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

0.29
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.

-0.26
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

0.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.57

Water Solubility

Log S (ESOL):?

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

-1.17
Solubility 12.3 mg/ml ; 0.0671 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.

-0.93
Solubility 21.5 mg/ml ; 0.117 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

-2.4
Solubility 0.738 mg/ml ; 0.00403 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.

-7.28 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

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)

2.24

Application In Synthesis of [ 180869-38-9 ]

* 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 [ 180869-38-9 ]

[ 180869-38-9 ] Synthesis Path-Downstream   1~17

  • 2
  • [ 180869-38-9 ]
  • [ 180869-39-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In water; at 48℃; for 17h; Step [B] : Preparation of 2-methylamino-pyrimidine-4- carbaldehyde (4-Dimethoxymethyl-pyrimidin-2-yl) -methylamine (Step A, 3.60 g, 19.6 mmol) and 3 N HCl (14.4 mL, 43.2 mmol) were combined and stirred at [48 C] for 17 h. After cooling to RT, 4.3 g of [NAHC03] was added in portions. The mixture was extracted with EtOAc, the combined organic portions were dried over [MGSO4,] filtered, and condensed to give the titled compound as a yellow solid. MS [(ES+)] : 138.3 (M+H) +. Calc'd for [C6H7N30-137.] 14.
With hydrogenchloride; at 60℃; for 2h; To the 2M solution of methylamine in THF (3 mL) 232 mg 4-(dimethoxymethyl)-2- methylsulfonyl-pyriinidine (Preparation 9a3, 1.00 mmol) was added and it was stirred at room temperature for lh. The reaction mixture was concentrated under reduced pressure, the residue was diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure. To the residue 3 mE 2N HC1 was added and it was stilTed at 60C for 2h. Than it was cooled to 0C, the pH was adjusted to 9 using 2N NaOH solution, and then 76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for lh. The reaction mixture was extracted with EtOAc, thecombined organic layers were dried over MgSO4 and concentrated under reduced pressure to give the title product.MS: (M+2H) 141.4.
  • 4
  • [ 180869-38-9 ]
  • Methyl-(4-[(Z)-3-morpholin-4-yl-propylimino]-methyl}-pyrimidin-2-yl)-amine [ No CAS ]
  • 5
  • [ 180869-38-9 ]
  • {4-[5-(4-Fluoro-phenyl)-3-(3-morpholin-4-yl-propyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-methyl-amine [ No CAS ]
  • 6
  • [ 67751-23-9 ]
  • [ 22661-87-6 ]
  • [ 180869-38-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In isopropyl alcohol; for 20h;Heating / reflux; Example 125 [N- (4, 4-DIMETHYL-1,] 2,3, [4-TETRAHYDRO-ISOQUINOLIN-7-YL)-2-[(2-] [ METHYLAMINO-PYRIMIDIN-4-YLMETHYL)-AMINO]-BENZAMIDE] Step A: Preparation of [(4-DIMETHOXYMETHYL-PYRIMIDIN-2-YL)-] methyl-amine A mixture of 1, 1-dimethoxy-4-dimethylaminobut-3-en-2- one (4.06 g, 22.3 mmol) (Lipinski; J. Het. Chem. (1995), 22, 1723), 1-methylguanidine hydrochloride (2.50 g, 22.3 mmol) and NaOH (0.89 g, 22.3 mmol) in 20 mL of IpOH and was stirred at reflux for 20 h. The mixture was cooled to RT, diluted with MeOH, and the solids were removed by filtration. The filtrate was condensed, and the crude compound was purified by flash column chromatography [(5%] to 40% of EtOAc in [CH2CL2).] The titled compound was obtained as a light yellowish oil. MS (ES+) : 184.2 [(M+H) +. CAL'D] for [CGH13N302-183.] 21.
  • 7
  • [ 6342-56-9 ]
  • [ 22661-87-6 ]
  • [ 4637-24-5 ]
  • [ 180869-38-9 ]
YieldReaction ConditionsOperation in experiment
Procedure J: Intermediate 8 (1-10) - 2-Methylaminopyrimidine-4- carboxaldehyde dimethyl acetal; [0097] A solution of 5.5 mL (41 mmol, 1.0 eq.) of dimethylformamide dimethyl acetal and 5.0 mL (41 mmol, 1.0 eq.) of pyruvic aldehyde dimethyl acetal was heated at 100 0C for 16 h. Methanol was removed in vacuo to afford a brown oil. To a solution of 15 mL of sodium ethoxide (21% in ethanol, 41 mmol, 1.0 eq.) was added 4.5 g (41 mmol, 1.0 eq.) of methyl guanidine HCl. The mixture was stirred for 10 min before a solution of the above described oil in 15 mL anhydrous ethanol was added. The mixture was heated to reflux for 24 h, allowed to cool to room <n="39"/>temperature and filtered. The solvent was removed in vacuo to afford 2- methylaminopyrimidine-4-carboxaldehyde dimethyl acetal (I- 10) as a dark brown oil which was used in the next step without further purification
  • 8
  • [ 874279-26-2 ]
  • [ 74-89-5 ]
  • [ 180869-38-9 ]
YieldReaction ConditionsOperation in experiment
at 20℃; for 1h; To the 2M solution of methylamine in THF (3 mL) 232 mg 4-(dimethoxymethyl)-2- methylsulfonyl-pyriinidine (Preparation 9a3, 1.00 mmol) was added and it was stirred at room temperature for lh. The reaction mixture was concentrated under reduced pressure, the residue was diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure. To the residue 3 mE 2N HC1 was added and it was stilTed at 60C for 2h. Than it was cooled to 0C, the pH was adjusted to 9 using 2N NaOH solution, and then 76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for lh. The reaction mixture was extracted with EtOAc, thecombined organic layers were dried over MgSO4 and concentrated under reduced pressure to give the title product.MS: (M+2H) 141.4.
  • 9
  • [ 180869-38-9 ]
  • [ 912470-42-9 ]
  • 10
  • [ 67751-23-9 ]
  • [ 180869-38-9 ]
  • 11
  • [ 180869-36-7 ]
  • [ 180869-38-9 ]
  • 12
  • [ 180869-38-9 ]
  • 2-(methylamino)pyrimidine-4-carbaldehyde hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In tetrahydrofuran; water; at 40℃; Aqueous 4 M HCI (2 ml) was added to a solution of 4-(dimethoxymethyl)-A/- methylpyrimidin-2-amine (0.060 g, 0.33 mmol) in THF (1 ml). The resulting mixture was heated to 40 C overnight and then cooled to room temperature. The reaction mixture containing the hydrochloride salt of the aldehyde was used directly in the next step without isolation.
  • 13
  • [ 165807-05-6 ]
  • [ 74-88-4 ]
  • [ 180869-38-9 ]
YieldReaction ConditionsOperation in experiment
67% In acetone; at 70℃;Inert atmosphere; Compounds 4-(dimethoxymethyl)pyrimidin-2-amine 68 8b (1.00 g, 5.65 mmol), 70 iodomethane (2.80 g, 19.77 mmol) and 71 acetone (30 mL) were mixed. This mixture were stirred for 16 h at 70 C., cooled to room temperature, and filtered. The solid was mixed with 10% 67 sodium hydroxide (8 mL), stirred for 0.5 h at 80 C., and cooled to room temperature. This mixture was quenched with 250 mL of 72 ice water, extracted with dichloromethane (50 mL×2), and the organic phase was washed with saturated brine (50 mL×2). The organic phase was dried over anhydrous sodium sulfate, filtered to remove the drying agent, and subjected to exsolution under reduced pressure, to obtain the target 73 product 8c 4-(dimethoxymethyl)-N-methylpyrimidin-2-amine 8c (0.70 g, yellow oil), at a yield of 67%. (0175) MS m/z (ESI): 184 [M+1] (0176) 1H NMR (400 MHz, CDCl3) delta 8.37 (d, J=4.8 Hz, 1H), 6.77 (d, J=5.2 Hz, 1H), 5.18 (brs, 1H), 5.13 (s, 1H), 3.42 (s, 6H), 3.03 (d, J=5.2 Hz, 3H).
  • 14
  • [ 102-09-0 ]
  • [ 180869-38-9 ]
  • phenyl (4-(dimethoxymethyl)pyrimidin-2-yl)(methyl)aminocarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
12% With lithium hexamethyldisilazane; In tetrahydrofuran; at 0℃; for 2h;Inert atmosphere; Compounds <strong>[180869-38-9]4-(dimethoxymethyl)-N-methylpyrimidin-2-amine</strong> 73 8c (0.20 g, 1.09 mmol), 25 diphenyl carbonate (0.47 g, 2.19 mmol), 26 lithium hexamethyldisilazide (1.5 mL, 1.51 mmol, 1 M solution in 27 tetrahydrofuran) and tetrahydrofuran (5 mL) were mixed and stirred for 2 h at 0 C. This mixture was quenched with 10 mL of a saturated ammonium chloride solution, extracted with ethyl acetate (20 mL×2), and the organic phase was washed with saturated brine (20 mL×2). The organic phase was dried over anhydrous sodium sulfate, and filtered to remove the drying agent. The residuals were purified through a preparative silica gel plate (dichloromethane/methanol 50:1), to obtain the target product phenyl (76 4-(dimethoxymethyl)pyrimidin-2-yl)(methyl) aminocarboxylate 8 d (40 mg, white solid), at a yield of 12%. (0178) MS m/z (ESI): 304 [M+1].
  • 15
  • [ 180869-38-9 ]
  • 3-(4-chloro-5-cyanopyrid-2-yl)-1-(4-(dimethoxymethyl)pyrimidin-2-yl)-1-methylurea [ No CAS ]
  • 16
  • [ 180869-38-9 ]
  • 3-(5-cyano-4-((2-methoxyethyl)amino)pyrid-2-yl)-1-(4-(dimethoxymethyl)pyrimidin-2-yl)-1-methylurea [ No CAS ]
  • 17
  • [ 180869-38-9 ]
  • 3-(5-cyano-4-((2-methoxyethyl)amino)pyrid-2-yl)-1-(4-formylpyrimidin-2-yl)-1-methylurea [ No CAS ]
 

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Technical Information

Categories

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