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Chemical Structure| 36314-97-3 Chemical Structure| 36314-97-3

Structure of 36314-97-3

Chemical Structure| 36314-97-3

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Product Details of [ 36314-97-3 ]

CAS No. :36314-97-3
Formula : C10H8ClN3
M.W : 205.64
SMILES Code : ClC1=NC(N)=NC(C2=CC=CC=C2)=C1
MDL No. :MFCD00030784
InChI Key :FIPBRZXDWSODDX-UHFFFAOYSA-N
Pubchem ID :240802

Safety of [ 36314-97-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 36314-97-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 56.88
TPSA ?

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

51.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.94
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

2.48
Log Po/w (WLOGP)?

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

2.39
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.

1.67
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

2.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.17

Water Solubility

Log S (ESOL):?

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

-3.25
Solubility 0.117 mg/ml ; 0.000568 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.

-3.21
Solubility 0.126 mg/ml ; 0.000613 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

-4.43
Solubility 0.00761 mg/ml ; 0.000037 mol/l
Class?

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

Moderately 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.

-5.79 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<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)

1.85

Application In Synthesis of [ 36314-97-3 ]

* 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 [ 36314-97-3 ]

[ 36314-97-3 ] Synthesis Path-Downstream   1~36

  • 1
  • [ 120-83-2 ]
  • [ 36314-97-3 ]
  • [ 78222-45-4 ]
  • 2
  • [ 36314-97-3 ]
  • 5-amino-2-(2-furyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidine [ No CAS ]
  • 3
  • [ 36314-97-3 ]
  • [ 78222-48-7 ]
  • 4
  • [ 36314-97-3 ]
  • [ 78222-46-5 ]
  • 5
  • [ 36314-97-3 ]
  • 2-amino-1-hydroxy-6-phenyl-4-pyrimidinone hydrochloride [ No CAS ]
  • 6
  • C11H8Cl2N2S [ No CAS ]
  • [ 36314-97-3 ]
  • [ 569658-29-3 ]
YieldReaction ConditionsOperation in experiment
40% With hydrogenchloride; In water; at 70℃; Examples 19-22; Using the following general method, Examples 19-22 were prepared; A suspension of Intermediate A (1.0 mmol), Intermediate B (1.0 mmol), and HCl (0.1 mL) in H2O (1.0 mL) was heated to 70 C. in a 5 mL reaction vial overnight. The reaction mixture was diluted with MeOH, treated with saturated NaHCO3, coated on silica and purified by MPLC (Biotage) with 5% MeOH in CH2Cl2.; Example 19; Preparation of N-(2-amino-6-phenyl-4-pyrimidinyl)-N-[3,5-dichloro-4-(4-pyridinylsulfanyl)phenyl]amine; Prepared in 40% yield from A17 and B14: TLC (4% MeOH in CH2Cl2) Rf 0.42; MS (ES) 440 [M+H]+; 1H-NMR (DMSO-d6) delta6.53 (s, 1H), 6.67 (bs, 2H), 6.94 (d, J=6.1 Hz, 2H), 7.47-7.51 (m, 3H), 7.93-7.96 (m, 2H), 8.18 (s, 2H), 8.36 (d, J=5.7 Hz, 2H), 9.88 (bs, 1H).
  • 7
  • [ 850250-63-4 ]
  • [ 36314-97-3 ]
  • N4-{4-[(2-ethylpyridin-4-yl)oxy]phenyl}-6-phenyl-pyrimidine-2,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% Example 1: Preparation of N-{4-[(2-ethylpyridin-4-yl) oxy] phenyl}-6-phenyl- pyrimidine-2,4-diamine Chloropyrimidine 1A (75 mg, 0.35 mmol) and aniline 2A (72 mg, 0.35 mmol) were suspended in water (2 mL) containing concentrated hydrochloric acid (0.1 mL) and stirred at 100 C for 17 h. After cooling to rt, the mixture was neutralized with 1 N aqueous sodium hydroxide and stirred for 20 min. The precipitate was collected by filtration and purified by silica gel column chromatography (0-5% methanol-methylene chloride) to afford 43 mg (32%) of the title compound as a yellow solid. 1H NMR (DMSO-d6) 8 9.34 (s, 1H), 8. 31 (d, 5.7 Hz, 1H), 7.91-7. 93 (m, 2H), 7.86 (d, J = 8. 8 Hz, 2H), 7.45-7. 47 (m, 3H), 7.07-7. 09 (m, 2H), 6.76 (d, J = 2.3 Hz, 1H), 6.68 (dd, J = 5.6 Hz, 1.3 Hz, 1H), 6.49 (s, 1H), 6.37 (b, 2H), 2.69 (q, J = 7.6 Hz, 2H), 1.19 (t, J = 7.4 Hz, 3H), MS ES 384 (M+H) +, calcd 384, RT = 1.87 min; TLC (5/95 v/v methanol-methylene chloride) Rf= 0.41. The reaction mixture can also be purified by preparative HPLC using an elution gradient from 15% to 85 % acetonitrile in water containing 0.1 % TFA over 15 min with Phenomenex Luna 5 ; j. CIS 150 x 30 mm column to provide the title compound as its TFA salt.
32% Chloropyrimidine IA (75 mg, 0.35 mmol) and aniline 2A (72 mg, 0.35 mmol) were suspended in water (2 mL) containing concentrated hydrochloric acid (0.1 mL) and stirred at 100 0C for 17 h. After cooling to rt, the mixture was neutralized with 1 N aqueous sodium hydroxide and stirred for 20 min. The precipitate was collected by filtration and purified by silica gel column chromatography (0-5% methanol-methylene chloride) to afford 43 mg (32%) of the title compound as a yellow solid. 1H NMR (DMSO-J6) delta 9.34 (s, IH), 8.31 (d, 5.7 Hz, IH), 7.91-7.93 (m, 2H), 7.86 (d, J = 8.8 Hz, 2H), 7.45-7.47 (m, 3H), 7.07-7.09 (m, 2H), 6.76 (d, J = 2.3 Hz, IH), 6.68 (dd, J = 5.6 Hz, 1.3 Hz, IH), 6.49 (s, IH), 6.37 (b, 2H), 2.69 (q, J = 7.6 Hz, 2H), 1.19 (t, J = 7.4 Hz, 3H), MS ES 384 (M+H)+, calcd 384, RT = 1.87 min; TLC (5/95 v/v methanol-methylene chloride) Rf= 0.41. The reaction mixture can also be purified by preparative HPLC using an elution gradient from 15% to 85 % EPO <DP n="53"/>acetonitrile in water containing 0.1 % TFA over 15 min with Phenomenex Luna 5 mu C18 150 x 30 mm column to provide the title compound as its TFA salt.By dissolving the title compound in an appropriate solvent such as MeOH or dioxane, addition of either 1 N HCl or 1 N methanesulfonic acid, and filtration, the corresponding HCl or methanesulfonate salt is isolated.
  • 8
  • [ 850250-66-7 ]
  • [ 36314-97-3 ]
  • 4-[4-(2-amino-6-phenylpyrimidin-4-ylamino)phenoxy]pyridine-2-carboxylic acid (2-hydroxyethyl)amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% Example 45: Preparation of 4- [4- (2-Amino-6-phenylpyrimidin-4- ylamino) phenoxy] pyridine-2-carboxylic acid (2-hydroxyethyl) amide; Chloropyrimidine 1A (0.2 g, 0.97 mmol) and Intermediate 2N (0.38 g, 0.97 mmol), were suspended in n-butanol (5 mL) and heated at 80 C for 12 h. LC-MS indicated that the reaction was complete. KF was then added to the reaction mixture and heating was continued at 80 C for 5 h. The solvent was removed by rotary evaporation, and the residue was treated with 10% sodium carbonate and extracted with EtOAc (20 mL x 3). The organic extracts were combined, washed with water and brine, dried over magnesium sulfate, and evaporated to afford a solid that was washed with methanol to give pure product, 0.19 g (44%).'H NMR (DMSO-d6) 8 9.36 (s, 1H), 8. 62 (t, 1H), 8.45 (d, 1H), 7. 88 (m, 4H), 7.47 (m, 3H), 7.38 (d, 1H), 7.11 (m, 3H), 6.45 (s, 1H), 6.34 (s, 2H), 3.49 (t, 2H), 3.36 (t, 2H); MS ES 443 (M+H) + calcd 443.
  • 9
  • [ 56741-94-7 ]
  • [ 36314-97-3 ]
YieldReaction ConditionsOperation in experiment
43% With trichlorophosphate; for 1h;Heating / reflux; Intermediate 1A : Preparation of 4-chloro-6-phenylpyrimidin-2-amine; A suspension of guanidine carbonate (3.60 g, 20 mmol) in ethanol (120 mL) and toluene (20 mL) was refluxed under nitrogen for 1 h, during which time about 50 mL of solvent was removed by distillation. After the mixture was cooled to 45 C, ethyl 3-oxo-3- phenylpropanoate (7.68 g, 40 mmol) was added and the solution was heated at reflux overnight. The desired product precipitated as a white solid during the reaction. Water (50 mL) was added to the reaction and the mixture was refluxed for an additional 30 min. After cooling to rt, the mixture was neutralized with 1N HC1 and placed in the refrigerator for 6 h. The solid was filtered, washed with water followed by ether and dried at 60 C under vacuum to give the product as white solid (6.45 g, 86%). MS ES: 188 (M+H) +, calcd 188; RT = 0.91 min; TLC (CH2C12/2M NH3 in MeOH 95/5) Rf = 0.10. A mixture of the above product (6.0 g, 32 mmol) and POC13 (100 mL) was heated at reflux for 1 h. The majority of the POC13 was removed in vacuo and the residue was diluted with EtOAc and poured over an ice/saturated NaHC03 solution. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried (Na2SO4), and concentrated. The crude organic concentrate was re-crystallized from EtOAc/ether to give the product 1A as an off-white powder (2. 8 g, 43%). MS ES: 206 (M+H) +, calcd 206; RT = 2.49 min; TLC (CH2C12/2M NH3 in MeOH 95/5) Rf = 0.72. (Reference 1: H. L. Skulnick, S. D. Weed, E. E. Edison, H. E. Renis, W. Wierenga, and D. A. Stringfellow, J ; Med. Cllem. 1985, 28,1854-1869).
3.49 g (86%) With ammonium hydroxide; In ice-water; trichlorophosphate; b 4-Chloro-6-phenyl-pyrimidin-2-ylamine A stirred suspension of 3.69 g (19.7 mmol) 2-amino-6-phenyl-3H-pyrimidin-4-one in 4.5 ml (49.2 mmol) phosphorus oxychloride was heated at reflux for 2 h. The reaction mixture was then cooled to about 70 C. and poured cautiously onto 20 ml rapidly stirred ice-water. The mixture was briefly warmed to room temperature and then was recooled to 0 C. 100 ml 25% ammonium hydroxide solution was added and the resulting crystals were collected by filtration and washed with ice-cold water and then with a little ether to afford 3.49 g (86%) 4-chloro-6-phenyl-pyrimidin-2-ylamine as a pale yellow crystalline solid. EI-MS m/e (%): 207 (M{37Cl}+, 35), 206 ([M{37Cl}-H]+, 30)., 205 (M{35Cl}+, 100), 204 ([M{35Cl}-H]+, 56), 170 ([M-Cl]+, 35), 128 (([M-C6H5]+, 85).
With trichlorophosphate; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; water; Example 1 Synthesis of 4-chloro-6-phenyl-2-pyrimidinamine; 2-amino-4-chloro-6-phenylpyrimidine To 10.0 g (53 mM) of 6-phenylisocytosine is added 80 ml of phosphorus oxychloride. The mixture is heated to reflux, and refluxed until solution is complete (about 30 minutes). The solution is then cooled and evaporated to dryness under vacuum at 45 C. The resulting oil is poured into 300 ml of ice water, with vigorous stirring, and the remaining oil washed into the aqueous mixture with additional 100 ml of water. The entire aqueous mixture is neutralized to pH 8 with concentrated ammonium hydroxide, filtered, and solids washed well with water until water wash is neutral. Dry at 60 in a vacuum oven to yield 9.2 g of 4-chloro-6-phenyl-2-pyrimidinamine.
  • 10
  • [ 850250-66-7 ]
  • [ 36314-97-3 ]
  • C27H30N6O3Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
In butan-1-ol; at 80℃; for 12h; Chloropyrimidine IA (0.2 g, 0.97 mmol) and Intermediate 2N (0.38 g, 0.97 mmol), were suspended in n-butanol (5 niL) and heated at 80 0C for 12 h. LC-MS indicated that the reaction was complete. KP was then added to the reaction mixture and heating was continued at 80 0C for 5 h. The solvent was removed by rotary evaporation, and the residue was treated with 10% sodium carbonate and extracted with EtOAc (20 mL x 3). The organic extracts were combined, washed with water and brine, dried over magnesium sulfate, and evaporated to afford a solid that was washed with methanol to give pure product, 0.19 g (44%). 1H NMR (DMSO-J6) delta 9.36 (s, IH), 8.62 (t, IH), 8.45 (d, IH), 7.88 (m, 4H), 7.47 (m, 3H), 7.38 (d, IH), 7.11 (m, 3H), 6.45 (s, IH), 6.34 (s, 2H), 3.49 (t, 2H), 3.36 (t, 2H); MS ES 443 (M+H)+ calcd 443.
  • 11
  • [ 871240-11-8 ]
  • [ 36314-97-3 ]
  • 6-phenyl-N4-(4-[2-(trifluoromethyl)pyrimidin-4-yl]oxy}phenyl)pyrimidine-2,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% 4-[2-(trifluoromethyl)pyrimidin-4-yl]oxy}aniline (1.0 g, 3.9 mmol) and 4-chloro-6- phenylpyrimidin-2-amine (806 mg, 3.9 mol) were suspended in water (39 mL) and isopropanol (13 mL) and the mixture was heated at 95 0C for 17 h. After cooling to rt, the mixture was neutralized with 1 N aqueous sodium hydroxide and stirred for 20 min. The precipitate were collected by filtration to afford 6-phenyl-N4-(4-[2- (trifluoromethyl)pyrimidm-4-yl]oxy}phenyl)pyrimidine-2,4-diamine (1.2 g, 72%) as a yellow solid. 1H NMR (DMSO-J6) delta 9.35 (s, IH), 8.85 (d, IH), 7.85-7.91 (m, 4H), 7.42- EPO <DP n="91"/>7.47 (m, 3H), 7.30 (d, IH), 7.18 (d, 2H), 6.48 (s, IH), 6.38 (brs, 2H); MS ES 425 (M+H)+, calcd 425, RT = 2.53 min.
  • 12
  • [ 56741-94-7 ]
  • [ 36314-97-3 ]
YieldReaction ConditionsOperation in experiment
43% With trichlorophosphate; for 1h;Heating / reflux; A suspension of guanidine carbonate (3.60 g, 20 mmol) in ethanol (120 mL) and toluene (20 mL) was refluxed under nitrogen for 1 h, during which time about 50 mL of solvent was removed by distillation. After the mixture was cooled to 45 0C, ethyl 3-oxo-3- phenylpropanoate (7.68 g, 40 mmol) was added and the solution was heated at reflux overnight. The desired product precipitated as a white solid during the reaction. Water (50 mL) was added to the reaction and the mixture was refluxed for an additional 30 min. After cooling to rt, the mixture was neutralized with IN HCl and placed in the refrigerator for 6 h. The solid was filtered, washed with water followed by ether and dried at 60 0C under vacuum to give the product as white solid (6.45 g, 86%). MS ES: 188 (M+H)+, calcd 188; RT = 0.91 min; TLC (CH2Cl2/ 2M NH3 in MeOH 95/5) Rf = 0.10.A mixture of the above product (6.0 g, 32 mmol) and POCl3 (100 mL) was heated at reflux for 1 h. The majority of the POCl3 was removed in vacuo and the residue was diluted with EtOAc and poured over an ice/saturated NaHCO3 solution. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried (Na2SO4), and concentrated. The crude organic concentrate was re-crystallized from EtO Ac/ether to give the product IA as an off-white powder (2.8 g, 43%). MS ES: 206 (M+H)+, calcd 206; RT = 2.49 min; TLC (CH2Cl2/ 2M NH3 in MeOH 95/5) Rf = 0.72. (Reference 1: H. L. Skulnick, S. D. Weed, E. E. Edison, H. E. Renis, W. Wierenga, and D. A. Stringfellow, J. Med. Chem. 1985, 28, 1854-1869).
With trichlorophosphate;Product distribution / selectivity; The following compounds presented in Examples 2-12 were prepared in accordance with Scheme 1, by a procedure analogous to that disclosed in Example 1, using starting materials with the appropriate substitution.
  • 13
  • [ 371-42-6 ]
  • [ 36314-97-3 ]
  • [ 881193-21-1 ]
YieldReaction ConditionsOperation in experiment
64% In isopropyl alcohol; at 80℃; for 6h; 4-(4-Fluoro-phenylsulfanyl)-6-phenyl-pyrimidin-2-ylamine was prepared from 4-Chloro-6-phenyl-pyrimidin-2-ylaniine (0.5 g, 2.44 mmol) using 4-fluorothiophenol (0.31 mg, 2.44 mmol) in zso-propanol (15 mL) at 800C for 6 hours. Yield: 64%. M.P.: 218-2200C.1H NMR (200 MHz, DMSO-J5): delta 7.94 (d, J= 6.2 Hz, 2H), 7.76 (d, J- 5.4 Hz, 2H), 7.74-7.34 (m5 5H), 6.50 (s, IH). LR: (KBr) 3489, 3246, 1674. MS: m/z (CI) 298 (M+, 100%).
  • 14
  • [ 36314-97-3 ]
  • [ 5345-54-0 ]
  • [ 881193-01-7 ]
YieldReaction ConditionsOperation in experiment
The following compounds presented in Examples 2-12 were prepared in accordance with Scheme 1, by a procedure analogous to that disclosed in Example 1, using starting materials with the appropriate substitution.
  • 15
  • [ 36314-97-3 ]
  • 4,5-dichloro-6-phenyl-2-pyrimidinamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-chloro-succinimide; In acetic acid; ethyl acetate; acetone; Example 7 Synthesis of 4,5-dichloro-6-phenyl-2-pyrimidinamine To 1.5 g (7.3 mM) of <strong>[36314-97-3]4-chloro-6-phenyl-2-pyrimidinamine</strong> is added 40 ml of glacial acetic acid and 1.05 g of N-chlorosuccinimide. The reaction is stirred at ambient temperature (-20 C.) for 18 hours. The reaction mixture is evaporated to dryness, dissolved in acetone and 10.0 g of silica gel added and the mixture evaporated to a powder under vacuum. The powder is chromatographed on 50 g silica gel and eluted with 35% ethyl acetate/hexane. A fraction containing material with a TLC r.f. of 0.7 35% ethylacetate/hexane is collected and evaporated to dryness, recrystallized from acetone/Skellysolve B (1:10), evaporated to dryness(?) to yield 0.90 g of 4,5-dichloro-6-phenyl-2-pyrimidinamine. Calculated for C10 H7 Cl2 N3: C, 50.03; H, 2.93; N, 17.50; Cl, 29.54. Found: C, 50.19; H, 2.98; N, 17.78; Cl, 29.50. H'-NMR: 7.83-7.36; 5.8-5.55.
  • 16
  • [ 109-01-3 ]
  • [ 36314-97-3 ]
  • [ 1028327-66-3 ]
  • 17
  • [ 36314-97-3 ]
  • [ 1186410-74-1 ]
YieldReaction ConditionsOperation in experiment
96% With hydrazine hydrate; In ethanol; for 24h; Step B - Synthesis of Compound 2cTo compound 2b (0.8g, 3.9mmol) was added EtOH (4OmL) and hydrazine hydrate (0.38mL, 7.78mmol) and the solution was stirred for 24h. Filtered solid, rinsed with MeOH, and dried to yield compound 2c (0.75g, 96%).
  • 18
  • [ 36314-97-3 ]
  • [ 1186410-27-4 ]
  • 19
  • [ 36314-97-3 ]
  • C17H15N5 [ No CAS ]
  • 20
  • [ 36314-97-3 ]
  • [ 1186410-75-2 ]
  • 21
  • [ 108-91-8 ]
  • [ 36314-97-3 ]
  • [ 1225058-31-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃; General procedure: General Procedure 1: To a mixture of <strong>[36314-97-3]4-chloro-6-phenylpyrimidin-2-amine</strong> (1 equiv.) is added Hunig?s base (3.4 equiv.) and an appropriate amine (1.6 equiv.) in DMF (500 pL). The mixture is heated at 120 00 overnight. The crude mixture is purified by preparative HPLC to afford the desired product.Example 14-N-cyclohexyl-6-phenylpyrimidine-2,4-diamine.Prepared according to general procedure 1 from cyclohexanamine and <strong>[36314-97-3]4-chloro-6-phenylpyrimidin-2-amine</strong>. LCMS [M+H] 269; 1H NMR (400 MHz, DMSO-d6) OH8.79-8.61 (1H, m), 7.78-7.67(2H, m), 7.66-7.55(3H, m), 6.33 (1H, s), 4.05-3.85 (1H, m), 2.00-1.83 (2H, m), 1.80-1.70 (2H, m), 1.41-1.10 (6H, m).
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃; General procedure: General Procedure 1: To a mixture of <strong>[36314-97-3]4-chloro-6-phenylpyrimidin-2-amine</strong> (1 equiv.) is added Hunig's base (3.4 equiv.) and an appropriate amine (1.6 equiv.) in DMF (500 muIota_). The mixture is heated at 120 C overnight. The crude mixture is purified by preparative HPLC to afford the desired product.
  • 22
  • [ 1279088-80-0 ]
  • [ 36314-97-3 ]
  • C18H19N5O [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 90℃; for 10h;Inert atmosphere; A mixture of 3-pyrazole boronate derivative (875 mg, 3.2 mmol), chloropyrimidine derivative (500 mg, 2.5 mmol) and K2C03 (1.04 g, 7.5 mmol) was suspendedin 10 mL DIVIF and 2.5 mL H20. The content was degassed by bubbling N2 through the solution. To this degassed reaction mixture was added Pd(PPh3)4 (290 mg, 0.25 mmol) and heated at 90 C for 1 Oh. After cooling the reaction to room temperature, 10 mL brine was added and the aqueous layer was extracted using EtOAc (2x25 mL). The pooled organic layer was dried over Na2SO4, concentrated and purified by silica gel chromatography to yield the desired product (522 mg,65%).
  • 23
  • [ 36314-97-3 ]
  • 6-(1-[6-(methoxymethyl)-2-pyridyl]methyl}-1H-pyrazol-3-yl)-4-phenyl-2-pyrimidinylamine [ No CAS ]
  • 24
  • [ 36314-97-3 ]
  • C13H11N5*ClH [ No CAS ]
  • 25
  • [ 103286-34-6 ]
  • [ 36314-97-3 ]
  • 7-((2-amino-6-phenylpyrimidin-4-yl)amino)-2-phenylphthalazin-1(2H)-one [ No CAS ]
  • 26
  • 7-amino-2-propargyl-phthalazin-1(2H)-one [ No CAS ]
  • [ 36314-97-3 ]
  • 7-((2-amino-phenylpyrimidin-4-yl)amino)-2-propargylphthalazin-1(2H)-one [ No CAS ]
  • 27
  • 7-amino-2-heptylphthalazin-1(2H)-one [ No CAS ]
  • [ 36314-97-3 ]
  • 7-((2-amino-6-phenylpyrimidin-4-yl)amino)-2-heptylphthalazin-1(2H)-one [ No CAS ]
  • 28
  • [ 94-02-0 ]
  • [ 36314-97-3 ]
  • 29
  • [ 36314-97-3 ]
  • C20H17ClN6 [ No CAS ]
  • 30
  • [ 36314-97-3 ]
  • 3-methyl-8-(2-methyl-6-(trifluoromethyl)pyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine [ No CAS ]
  • 31
  • [ 36314-97-3 ]
  • 4-chloro-5-iodo-6-phenylpyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With N-iodo-succinimide; acetic acid; for 16h; 4-Chloro-6-phenylpyrimidin-2-amine 1a (2 g, 9.75 mmol, prepared according to the known method disclosedin "Bioorganic & Medicinal Chemistry Letters, 2011, 21(8), 2497-2501") and N-iodosuccinimide (2.6 g, 11.7 mmol) weredissolved in 30 mL of acetic acid. After completion of the addition, the reaction solution was stirred for 16 hours. Thereaction solution was added with 200 mL of saturated sodium bicarbonate solution, and extracted with ethyl acetate(100 mL33). The organic phases were combined, washed with saturated sodium chloride solution (100 mL), dried overanhydrous sodium sulfate, and filtrated to collect the filtrate. The filtrate was concentrated under reduced pressure, andthe residue was purified by silica gel chromatography with eluent system B to obtain the title compound 1b (2.88 g, yield:89%).MS m/z (ESI): 332.2 [M+1]
65.5% With N-iodo-succinimide; acetic acid; at 0℃; for 17h; Compound 1e (1.51 g, 7.34 mmol) was dissolved in 30 mL of acetic acid, and N-iodosuccinimide (1.82 g, 8.08 mmol) was added at 0 C, and the reaction was stirred for 17 hours. Stop the reaction, and adjust the pH to more than 7 with a saturated solution of sodium bicarbonate.Extracted with ethyl acetate (100 mL×3),The residue was purified by silica gel chromatography using eluent B.The title compound 1f (1.59 g, yield: 65.5%) was obtained.
31% With N-iodo-succinimide; In N,N-dimethyl-formamide; at 80℃; for 16h; Into a 250-mL round-bottom flask were placed <strong>[36314-97-3]4-chloro-6-phenylpyrimidin-2-amine</strong> (4.2 g, 20.4 mmol), NIS (9.2 g, 40.9 mmol) and DMF (100 mL). The resulting mixture was stirred for 16 h at 80 C. After cooling, the reaction mixture was quenched with 100 mL of water. The resulting mixture was extracted with 3 x 50 mL of ethyl acetate. The combined organic layers were washed with 2 x 50 mL of H20, 50 mL of brine, then dried over anhydrous sodium sulfate and concentrated. The residue was purified on silica gel column with ethyl acetate/petroleum ether (1/1) to obtain 2.1 g (31.0%) of 4-chloro-5-iodo-6-phenylpyrimidin-2-amine as a brown solid. ES-MS (m/z): [M+l]+ = 332.
  • 32
  • [ 36314-97-3 ]
  • 4-chloro-5-(2-methyl-6-(trifluoromethyl)pyridin-4-yl)-6-phenylpyrimidin-2-amine [ No CAS ]
  • 33
  • [ 36314-97-3 ]
  • 4-hydrazinyl-5-(2-methyl-6-(trifluoromethyl)pyridin-4-yl)-6-phenylpyrimidin-2-amine [ No CAS ]
  • 34
  • [ 36314-97-3 ]
  • 8-(2-methyl-6-(trifluoromethyl)pyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine [ No CAS ]
  • 35
  • [ 36314-97-3 ]
  • 8-(2-methyl-6-(trifluoromethyl)pyridin-4-yl)-7-phenyl-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine [ No CAS ]
  • 36
  • [ 36314-97-3 ]
  • 5-bromo-4-hydrazinyl-6-phenylpyrimidin-2-amine [ No CAS ]
 

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Technical Information

Categories

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