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Chemical Structure| 598-50-5 Chemical Structure| 598-50-5
Chemical Structure| 598-50-5

1-Methylurea

CAS No.: 598-50-5

4.5 *For Research Use Only !

Cat. No.: A173396 Purity: 97%

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Product Details of [ 598-50-5 ]

CAS No. :598-50-5
Formula : C2H6N2O
M.W : 74.08
SMILES Code : O=C(N)NC
MDL No. :MFCD00007950
InChI Key :XGEGHDBEHXKFPX-UHFFFAOYSA-N
Pubchem ID :11719

Safety of [ 598-50-5 ]

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

Calculated chemistry of [ 598-50-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 5
Num. arom. heavy atoms 0
Fraction Csp3 0.5
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 17.83
TPSA ?

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

55.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.69
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

-1.4
Log Po/w (WLOGP)?

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

-0.72
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.

-0.96
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

-1.22
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.72

Water Solubility

Log S (ESOL):?

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

0.65
Solubility 330.0 mg/ml ; 4.45 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

0.74
Solubility 411.0 mg/ml ; 5.55 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.23
Solubility 124.0 mg/ml ; 1.68 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.

-7.75 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

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

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)

1.0

Application In Synthesis of [ 598-50-5 ]

* 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 [ 598-50-5 ]

[ 598-50-5 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 57-10-3 ]
  • [ 598-50-5 ]
  • [ 7388-58-1 ]
  • [ 629-54-9 ]
  • 2
  • [ 598-50-5 ]
  • [ 3147-45-3 ]
  • 3
  • [ 92-55-7 ]
  • [ 141-97-9 ]
  • [ 598-50-5 ]
  • [ 14757-94-9 ]
  • 4
  • [ 90-63-1 ]
  • [ 598-50-5 ]
  • [ 22199-48-0 ]
  • 5
  • [ 381-98-6 ]
  • [ 598-50-5 ]
  • [ 90715-80-3 ]
  • [ 85199-73-1 ]
  • [ 85199-74-2 ]
  • 6
  • [ 381-98-6 ]
  • [ 598-50-5 ]
  • [ 85199-73-1 ]
  • [ 85199-74-2 ]
  • 7
  • [ 1627-27-6 ]
  • [ 7732-18-5 ]
  • potassium permanganate [ No CAS ]
  • [ 89281-42-5 ]
  • [ 144-62-7 ]
  • [ 598-50-5 ]
  • 8
  • [ 598-50-5 ]
  • [ 108-46-3 ]
  • ZnCl2 [ No CAS ]
  • [ 3147-45-3 ]
  • 9
  • [ 381-98-6 ]
  • [ 598-50-5 ]
  • [ 90715-80-3 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; EXAMPLE 9 STR24 A mixture of alpha-trifluoromethylacrylic acid (700 mg; 5.0 mmoles) and methylurea (407 mg; 5.5 mmoles) in DMF (3 ml) was heated at 90 C. with stirring for 4 hours. DMF was evaporated under reduced pressure. The residue was purified by a column chromatography on silica gel to give 118 mg (yield 12%) of 1-methyl-5-trifluoromethyl-5,6-dihydrouracil (OF-3), 20 mg (yield: 2%) of 3-methyl-5-trifluoromethyl-5,6-dihydrouracil and 706 mg (yield: 66%) of 1-(2-hydroxycarbonyl-3,3,3-trifluoropropyl)-3-methylurea. 1-(2-Hydroxycarbonyl-3,3,3-trifluoropropyl)-3-methylurea: m.p.: 149.5-150.5 C. Mass spectrum: m/e (relative intensity) M+ 214(9), 30 (100). IR (KBr): 3430, 3400 cm-1 (nuN--H), 3600-2200 cm-1 (nuO--H). 1740, 1725, 1610 cm-1 (nuc=o). 1 H NMR (CD3 COCD3:TMS): delta2.70(s, 3H), 3.3-3.8(m, 3H), 5.9(bs, 1H). 6.1(bs, 1H), 10.7(bs, 1H). 19 F NMR (CD3 COCD3:CFCl3): delta-66.1(m).
  • 10
  • [ 674-82-8 ]
  • [ 598-50-5 ]
  • [ 1627-27-6 ]
YieldReaction ConditionsOperation in experiment
18% at 100℃; for 18h;Inert atmosphere; Step 1 : 1 ,6-dimethylpyrimidine-2,4(l H,3H)-dioneA solution of 1-methylurea (30 g, 0.356 mol) in 4-methyleneoxetan-2-one (26.4 g, 0.356 mol) was heated at 100C for 18 h, cooled to RT then diluted with MeOH (50 mL). The reaction was filtered and the filtered solid was washed with MeOH (20 mL) and dried to give 1,6- dimethylpyrimidine-2,4(lH,3H)-dione (9 g, 8% yield) as a white solid. ]H NMR (CDClj) 6: 8.33 (s, 1H), 5.58 (s, 1H), 3.38 (s, 3H), 2.26 (s, 3H). LCMS: MH+ 141 and TR = 0.368 min. Used without further purification.
14% In acetic acid; at 120℃; for 12h; 4-Methyleneaxetan-2-one (8.0 g, 95 mmol) and N-methylurea (5.0 g, 68 mmol) were dissolved in acetic acid (50 ml), followed by stirring at 120 C. for 12 hours. The solvent was removed under reduced pressure. To the obtained residue, ethyl acetate (50 ml) was added, followed by stirring for 30 minutes. After the precipitated solid was filtered, purification was conducted by reversed-phase HPLC (H2O containing 0.1% FTA/CH3CN system) to obtain the title compound (1.3 g, 14%). [0618] 1H NMR (400 MHz, CD3OD): δ 5.59 (s, 1H), 3.39 (s, 3H), 2.32 (s, 3H)
  • 11
  • [ 18643-86-2 ]
  • [ 598-50-5 ]
  • [ 934050-55-2 ]
YieldReaction ConditionsOperation in experiment
70% With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 100℃; for 2h; Example 14N-hydroxy-3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide; Compound I-286 Step 1: methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate Intermediate-5To a solution of <strong>[18643-86-2]dimethyl 2-bromoterephthalate</strong> (0.25 g, 0.92 mmol) and methylurea (88.2 mg, 1.19 mmol) in 1,4-dioxane (7 mL) was added cesium carbonate (0.60 g, 1.83 mmol). 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (53.0 mg, 0.092 mmol) was then added followed by tris(dibenzylideneacetone)dipalladium (42 mg, 0.046 mmol). The reaction mixture was heated to 100 C. and stirred for 2 d. The mixture was then cooled to rt and concentrated. Water was added and the remaining solid was filtered. The collected solid was then washed with DCM (3×) to afford methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate (0.15 g, 70%). LC-MS: (FA) ES+235; 1H NMR (400 MHz, DMSO) δ 11.63 (s, 1H), 8.05 (d, J=8.2 Hz, 1H), 7.77 (d, J=1.4 Hz, 1H), 7.71 (dd, J=8.2, 1.5 Hz, 1H), 3.89 (s, 3H), 3.26 (s, 3H).
58.3% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 120℃; for 16h; To a solution of <strong>[18643-86-2]dimethyl 2-bromoterephthalate</strong> (3.00 g, 10.99 mmol) and 1-methylurea (1.06 g, 14.28 mmol) in 1,4-dioxane (10.0 mL) was added cesium carbonate (7.16 g, 21.97 mmol), xantphos (0.64 g, 1.099 mmol) and tris(dibenzylideneacetone)dipalladium(0) (1.00 g, 1.099 mmol). The reaction mixture was heated to 120C for 16 h. The reaction mixture was then cooled to room temperature and concentrated to afford crude solid. To the crude solid add 60.0 mL dichloromethane and stirred it for 5 minutes. Filtered this reaction mixture to get crude solid which was purified by column chromatography using eluent 0-10% of methanol in dichloromethane to afford the titled compound methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate 1.5 g, 58.3 % yield as a light yellow solid. MS (ES+) m/z = 235.27 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.80 - 7.67 (m, 2H), 3.90 (s, 3H), 3.27 (s, 3H).
  • 12
  • [ 451-40-1 ]
  • [ 178686-24-3 ]
  • [ 598-50-5 ]
  • [ 1283117-08-7 ]
YieldReaction ConditionsOperation in experiment
15.2% With hydrogenchloride; In ethanol; water; for 72.0h;Reflux; [00156] A mixture of 1,2-diphenylethanone (400 mg, 2.04 mmol), 3-ethoxy-4- hydroxy- 5 -nitrobenzaldehyde (430 mg, 2.04 mmol), and 1-methylurea (454 mg, 6.12 mmol) in anhydrous EtOH was added concentrated HC1 (204 mg, 2.04 mmol), and the reaction mixture was refluxed for 3 days. When TLC (EtOAc:MeOH=10: l) showed that the starting materials were consumed, the reaction mixture was concentrated, and purified by preparative HPLC to afford Compound 11 as a yellow solid (138 mg, yield: 15.2%). 1H NMR (DMSO- d6 400 MHz TMS): delta 10.25 (s, 1H), 7.68 (d, J = 2.8 Hz, 1H), 7.45 (s, 1H), 7.20-7.28 (m, 3H), 7.15-7.20 (m, 3H), 6.85-6.95 (m, 3H), 6.70 (d, J = 6.4 Hz, 1H), 5.00 (d, J = 2.4 Hz, 1H), 4.02 (m, 2H), 2.60 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H); MS (ESI): m/z 446.2 [M+l]+.
 

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