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Chemical Structure| 7752-72-9 Chemical Structure| 7752-72-9
Chemical Structure| 7752-72-9

5-Chloro-6-methylpyrimidin-4(3H)-one

CAS No.: 7752-72-9

4.5 *For Research Use Only !

Cat. No.: A104634 Purity: 95%

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Product Details of [ 7752-72-9 ]

CAS No. :7752-72-9
Formula : C5H5ClN2O
M.W : 144.56
SMILES Code : O=C1NC=NC(C)=C1Cl
MDL No. :MFCD08234409
InChI Key :YIDUVRHFPFLCLN-UHFFFAOYSA-N
Pubchem ID :135512950

Safety of [ 7752-72-9 ]

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

Calculated chemistry of [ 7752-72-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 34.83
TPSA ?

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

45.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.09
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

0.5
Log Po/w (WLOGP)?

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

0.73
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.

0.38
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

2.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.97

Water Solubility

Log S (ESOL):?

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

-1.54
Solubility 4.13 mg/ml ; 0.0285 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.

-1.03
Solubility 13.5 mg/ml ; 0.0932 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

-2.54
Solubility 0.418 mg/ml ; 0.00289 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

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.

-6.83 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)

1.44

Application In Synthesis of [ 7752-72-9 ]

* 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 [ 7752-72-9 ]

[ 7752-72-9 ] Synthesis Path-Downstream   1~28

YieldReaction ConditionsOperation in experiment
0.7 g (22%) Step A: Preparation of 5-Chloro-6-hydroxy-4-methylpyrimidine Under N2, a solution of ethyl 2-chloroacetoacetate (1.8 ml, d=1.15, 0.013 mol) in CHCl3 (50 ml) was added dropwise to a solution 4-methoxybenzamidine (3.9 g, 0.026 mol) in CHCl3 (100 ml). After stirring overnight, the reaction mixture was filtered and the filtrate was washed with dilute NaOH solution. The aqueous layer was extracted with CH2 Cl2 (3*) and the organic layer was dried, filtered and concentrated to dryness. The residue was chromatographed on silica gel and the product was eluted with 2% CH3 OH-CHCl3 (v/v) to yield 0.7 g (22%) of product m.p. 250-251 C.
(2) The compound prepared in reference example 3-(1) (5.0g, 45mmol) was dissolved in acetic acid (5ml), and chlorine gas generated by potassium permanganate (11g) and concentrated hydrochloric acid (70ml) was bubbled through the reaction mixture at or below 15 ØC. After the reaction mixture was stirred at room temperature for 1 hour, the crystal separated was collected by filtration, and dried to give 5-chloro-4-hydroxy-6-methylpyrimidine (6.8g). 1H-NMR(DMSO-d6) delta 2.33(3H, s), 8.08(1H, s).
  • 2
  • α-chloro-β-aminocrotonic acid methyl ester [ No CAS ]
  • [ 7752-72-9 ]
YieldReaction ConditionsOperation in experiment
16.6 g (67.5%) With sodium methylate; formamide; In methanol; Example 11 5-Chloro-4-hydroxy-6-methylpyrimidine 25.9 g (0.17 mol) of methyl 3-amino-2-chloro-2-butenoate are reacted with 11.7 g (0.26 mol) of formamide and 51 ml of sodium methylate solution in 20 ml of methanol and worked up in analogy to Example 9 (reaction time 20 h). Yield: 16.6 g (67.5%)
  • 3
  • [ 109-64-8 ]
  • [ 7752-72-9 ]
  • 4-(3-bromopropoxy)-5-chloro-6-methylpyrimidine [ No CAS ]
  • 4
  • [ 6313-33-3 ]
  • [ 609-15-4 ]
  • [ 7752-72-9 ]
  • 5
  • [ 7752-72-9 ]
  • 5-chloro-4-methyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine [ No CAS ]
  • 6
  • [ 609-15-4 ]
  • [ 463-52-5 ]
  • [ 7752-72-9 ]
YieldReaction ConditionsOperation in experiment
66% 1) The Preparation of 4-hydroxyl-5-chloro-6-methylpyrimidine 8.80 g (0.16 mol) of CH3ONa in methanol was added slowly to a solution of 11.30 g (0.11 mol) of formimidamide in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 h after addition at room temperature. Followed by addition of 11.17 g (0.068 mol) of ethyl 2-chloro-3-oxobutanoate, the mixture was continued stirring for another 5-7 h at room temperature. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HCl, and then filtered to afford orange-yellow solid, the water phase was extracted with ethyl acetate (3*50 ml), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was dissolved to 50 ml of ethyl acetate, stand overnight to obtain 6.48 g as orange-yellow solid with yield of 66%, m.p, 181184 C.
  • 7
  • [ 7752-72-9 ]
  • [ 83942-10-3 ]
YieldReaction ConditionsOperation in experiment
88.5% With trichlorophosphate; In toluene;Reflux; 2) The Preparation of Intermediate 4,5-dichloro-6-methylpyrimidine 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 ml), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column to give 14.43 g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; The preparation of intermediate 4,5-dichloro-6-methylpyrimidine ;50ml of POCl3 was added dropwise to a solution of 14.5g ( 0.lmol ) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 hrs after addition. ;After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. ;The water phase was extracted with ethyl acetate (3x50mL), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column to give 14.43g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Enzymatic reaction; 2) Preparation of 4,5-dichloro-6-methylpyrimidineThe 14.5g (0.1mol) <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml of phosphorus oxychloride dropwise at reflux temperature the reaction completion 5-7 hours after, TLC monitored the reaction is complete. The toluene was evaporated under reduced pressure and an excess of phosphorus oxychloride, while stirring the reaction was poured into ice water, the aqueous phase was extracted with (3 × 50ml) and extracted with ethyl acetate, the combined organic phase was dried over anhydrous magnesium sulfate, filtered, desolvation . The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether (boiling range 60-90 ), the volume ratio of 1: 4) was isolated as a yellow liquid 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene; at 5 - 7℃;Reflux; 14.5g (0.1mol) 4- hydroxy-5-chloro-6-methylpyrimidine dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml phosphorus oxychloride, after dropwise addition the reaction heated at reflux for 5-7 hours, TLC monitored after completion of the reaction. Toluene was evaporated under reduced pressure and excess phosphorus oxychloride, with stirring the reaction was poured into ice water, the aqueous phase was extracted with ethyl acetate (3 × 50ml), the combined organic phase was dried over anhydrous magnesium sulfate, filtered, and dissolved. The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether (boiling range 60-90 deg. C), the volume ratio of 1: 4) was isolated as a yellow liquid 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; The 14.5g (0.1mol) 4- hydroxy-5-chloro-6-methylpyrimidine dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml of phosphorus oxychloride dropwise at reflux temperature the reaction completion 5-7 hours . After completion of the reaction was monitored by TLC, toluene was distilled off under reduced pressure and an excess of phosphorus oxychloride, while stirring the reaction was poured into ice water, the aqueous phase was extracted with (3 × 50ml) and extracted with ethyl acetate, the combined organic phase was dried over anhydrous magnesium dried, filtered, removing solvent. The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether, the volume ratio of 1: 5) was isolated yellow liquid 14.43 g, 88.5% yield.
88.5% With trichlorophosphate; In toluene;Reflux; 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 mL), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether=1:5, as an eluent) to give 14.43 g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.45 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50 ml of toluene and stir it under anti-flask50 ml of phosphorus oxychloride was added dropwise, and the reaction was heated to reflux for 5-7 hours. TLC was monitored after the reaction was completed. Vacuum distillation of toluene andThe amount of phosphorous oxychloride was poured into ice water with stirring, the aqueous phase was extracted with (3×50 ml) ethyl acetate, and the organic phases were combined.Anhydrous magnesium sulfate drying and desolventization. Chromatographic separation of the yellow liquid 14.43g, the yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50 ml of toluene, add 50 ml ofphosphorus oxychloride to the reaction flask with stirring, and then heat up to reflux for 5-7 hours. After TLC monitoring was completed, toluene and excess phosphorus oxychloride were distilled off underreduced pressure. The reaction was poured into ice water with stirring. The aqueous phase was extracted with(3×50 ml) ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate.Dry, filter, and dissolve. The residue was purified by column chromatography (eluent: ethyl acetate and petroleum ether, 1 : 5 in volume) to give 14.43 g of a yellow liquid, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 mL), the organic phases were merged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether=1:5, as an eluent) to give14.43 g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> was dissolved in 50 ml of toluene solution.50 ml of phosphorus oxychloride was added dropwise to the reaction flask under stirring, and the mixture was heated under reflux for 5-7 hours.After the TLC monitoring reaction was completed, toluene and excess phosphorus oxychloride were distilled off under reduced pressure, and the reactant was poured into ice water with stirring.The aqueous phase was extracted with ethyl acetate (3 × 50ml), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, desolventized.Residue column chromatography (eluent is ethyl acetate and petroleum ether,Volume ratio of 1: 5) to give yellow liquid was isolated 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.5g (0.1mol) <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50ml toluene solution,Under stirring, 50ml of phosphorus oxychloride was dropped into the reaction bottle, and the temperature was raised and the reaction was refluxed for 5-7 hours.After the reaction was monitored by TLC, toluene and excess phosphorus oxychloride were distilled off under reduced pressure.The reaction was poured into ice water with stirring, the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered and desolvated.The residue was separated by column chromatography (eluent was ethyl acetate and petroleum ether, volume ratio was 1: 5) to obtain a yellow liquid 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.5g (0.1mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50ml of toluene solution, drop 50ml of phosphorus oxychloride into the reverse bottle with stirring, and after heating up, reflux and react for 5-7 hours , After the reaction was monitored by TLC. Toluene and excess phosphorus oxychloride were distilled off under reduced pressure, the reaction was poured into ice water with stirring, the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered and desolvated . Column chromatography of the residue (eluent is ethyl acetate and petroleum ether (boiling range 60-90 C), volume ratio is 1: 5) to obtain a yellow liquid 14.43g, yield 88.5%.
With trichlorophosphate; In toluene;Reflux; General procedure: POCl3 (100 mL) was added dropwise to a solution of M-2 (0.36 mol)in toluene (150 mL), the mixture was refluxed for 3-5 h. The reactionmixture was concentrated under reduced pressure to remove tolueneand extra POCl3, and then poured into ice water. The water phase wasextracted with ethyl acetate (3 × 50 mL), the emerged organic phasewas successively washed with saturated sodium bicarbonate, dried overanhydrous magnesium sulfate, filtered and then concentrated underreduced pressure. The residue was purified through silica column togive M-3 as yellow liquid.

  • 8
  • [ 7752-72-9 ]
  • C14H14ClN3O2 [ No CAS ]
  • 9
  • [ 7752-72-9 ]
  • C14H14ClN3O2*ClH [ No CAS ]
  • 10
  • [ 3473-63-0 ]
  • [ 609-15-4 ]
  • [ 7752-72-9 ]
YieldReaction ConditionsOperation in experiment
66% The preparation of 4-hydroxyl-5-chloro-6-methylpyrimidine ;8.80g (0.16mol) of CH3ONa in methanol was added slowly to a solution of 11.30g (0.11mol of formimidamide in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 hrs after addition at room temperature. ;Followed by addition of 11.17g ( 0.068mol ) of ethyl 2-chloro-3-oxobutanoate, the mixture was continued stirring for another 5-7 hrs at room temperature. ;After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HCl, and then filtered to afford orange-yellow soilid, the water phase was extracted with ethyl acetate (3x50mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. ;The residue was dissolved to 50ml of ethyl acetate, stand overnight to obtain 6.48g as orange-yellow soilid with yield of 66%. m.p. 181~184C.
66% 1) Preparation of 4-hydroxy-5-chloro-6-methylpyrimidineStirring at room temperature to a solution of methanol 50ml 11.30g (0.11mol) of formamidine acetate was added slowly dropwise 8.80g (0.16mol) of sodium methoxide methanol solution was dropwise completed stirring was continued at room temperature 2h. To the above solution was then added dropwise 11.17g (0.068mol) of 2-chloroacetyl ethyl acetate, the reaction was stirred for 5-7 hours at room temperature continued, monitored by TLC after completion of the reaction, the solvent was distilled off under reduced pressure, adjusted to pH = 5 with hydrochloric acid 1-6, orange solid was suction filtered, the aqueous phase with (3 × 50ml) and extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered, and desolvation. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66%, m.p. 181 ~ 184 .
66% With stirring at room temperature, to 11.30g (0.11mol) of formamidine acetate in 50ml of methanol was slowly added dropwise 8.80g (0.16mol) of methanol solution of sodium methoxide, after dropwise addition, at room temperature and stirring was continued for 2h. To the above solution was then added dropwise 11.17g (0.068mol) of intermediate ethyl 2-chloroacetoacetate, continued stirring for 5-7 hours at room temperature. After completion of the reaction monitored by TLC, the solvent was distilled off under reduced pressure, adjusted with hydrochloric acid pH = 5 ~ 6, orange solid was suction filtered, the aqueous phase was extracted with ethyl acetate (3 × 50ml), dried over anhydrous magnesium sulfate, filtered, removing solvent. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66%, m.p. 181 ~ 184 deg. C.
66% Stirring at room temperature to a solution of methanol 50ml 11.30g (0.11mol) of formamidine acetate was added slowly dropwise 8.80g (0.16mol) of sodium methoxide in methanol, stirring was continued at room temperature completion of dropwise 2h. Then added dropwise 11.17g (0.068mol) ethyl 2-chloroacetoacetate intermediate to the above solution, the reaction was stirred for 5-7 hours at room temperature continued. After completion of the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, adjusted to pH = 5 with hydrochloric acid to 6, orange solid was suction filtered, the aqueous phase with (3 × 50ml) and extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered off solution. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66%
66% To a solution of 11.30 g (0.11 mol) methylhydrazine acetate in 50 ml of methanol was slowly added dropwise 8.80 g with stirring at room temperature.(0.16 mol) of sodium methoxide in methanol, and the mixture was stirred at room temperature for 2 h. Then 11.17 g (0.068 mol) was added dropwise to the above solution.Ethyl 2-chloro-acetoacetate was stirred at room temperature for 5-7 hours. After TLC monitoring was completed, the solvent was distilled off under reduced pressure and salt was used.The pH was adjusted to 5-6, and the orange solid was filtered by suction. The aqueous phase was extracted with ethyl acetate (3×50 ml), dried over anhydrous magnesium sulfate, and dissolved.The combined product was dissolved in 50 ml of ethyl acetate, allowed to stand overnight and filtered to give 6.48 g of an orange-yellow solid. Yield 66.0%
66% A solution of 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise to a solution of 11.30 g (0.11 mol) of methylacetoacetate in 50 ml of methanol at room temperature with stirring, and the mixturewas stirred at room temperature for 2 hours. Then, 11.17 g (0.068 mol) of the intermediate 2-chloroacetoacetic acid ethylacetate was added dropwise to theabove solution, and the reaction was continued for 5-7 hours while stirring at room temperature. After the TLCmonitoring reaction was completed, the solvent was evaporated under reduced pressure, and the pH wasadjusted to 5-6 with hydrochloric acid. The orange solid was collected by suction filtration, and the aqueousphase was extracted with ethyl acetate (3×50 ml), dried over anhydrous magnesium sulfate, filtered and shaken.Dissolved. The residue was dissolved in 50 ml of ethyl acetate, allowed to stand overnight and filtered to give 6.48g of an orange-yellow solid. The yield of 66%.
66% 10343] A solution of 8.80 g (0.16 mol) of CH3ONa in methanol was added slowly to a solution of 11.30 g (0.11 mol) of formimidamideacetate in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 h after addition at room temperature. Followed by addition of 11.17 g (0.068 mol) of ethyl 2-chloro-3-oxobu- tanoate, the mixture was continued stirring for another 5-7 h at room temperature. Afier the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HC1, and then filtered to afford orangeyellow solid, the water phase was extracted with ethyl acetate (3x50 mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was dissolved to 50 ml of ethyl acetate, stand overnight to obtain 6.48 g as orange-yellow solid with yield of 66%. m.p. 181-184 C.
66% To a solution of 11.30 g (0.11 mol) of formamidine acetate in 50 ml of methanol, a solution of 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise with stirring at room temperature.Stirring was continued for 2 h at room temperature.Then, 11.17 g (0.068 mol) of an intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was further stirred at room temperature for 5-7 hours.After the TLC monitoring reaction was completed, the solvent was evaporated under reduced pressure, and the mixture was adjusted to pH 5 to 6 with hydrochloric acid, and filtered to give an orange-yellow solid.The aqueous phase was extracted with (3 × 50ml) of ethyl acetate, dried over anhydrous magnesium sulfate, filtered, desolventized.The residue was dissolved in 50ml of ethyl acetate, allowed to stand overnight, and filtered to give an orange-yellow solid 6.48g. Yield 66%,
66% To a solution of 11.30 g (0.11 mol) formamidine acetate in 50 ml of methanol under stirring at room temperature, 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise, and stirring was continued at room temperature for 2 h.Then, 11.17 g (0.068 mol) of intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was continued to be stirred at room temperature for 5-7 hours.After the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, and the pH was adjusted to 5-6 with hydrochloric acid.Filtration with suction yielded an orange-yellow solid, and the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, dried over anhydrous magnesium sulfate, filtered and desolvated.The residue was dissolved in 50 ml of ethyl acetate, left overnight, and filtered to obtain 6.48 g of orange solid. The yield is 66%,
66% To a solution of 11.30 g (0.11 mol) formamidine acetate in 50 ml of methanol under stirring at room temperature, 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise, and stirring was continued at room temperature for 2 h. Then, 11.17g (0.068mol) of intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was stirred at room temperature for 5-7 hours. After the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, and the pH was adjusted to 5 with hydrochloric acid. 6, suction filtration to obtain orange-yellow solid, the aqueous phase was extracted with (3 × 50ml) ethyl acetate, dried over anhydrous magnesium sulfate, filtered and desolvated. The residue was dissolved in 50 ml of ethyl acetate, left overnight, and filtered to obtain 6.48 g of orange solid. 66% yield
With sodium methylate; In methanol; at 5 - 20℃; General procedure: A solution of formamidine acetate (0.70 mol) in methanol (150 mL)was stirred at 5-10 C, and then CH3ONa (1.20 mol) in methanol(150 mL) newly prepared was added slowly under stirring, followed byaddition of M-1 (0.50 mol) in methanol (100 mL). The mixture wascontinued stirring for another 3-4 h at room temperature and thenconcentrated under reduced pressure. The residue was adjusted to pH5-6 with diluted HCl, the precipitated solid was filtered to afford M-2 asa white solid.

  • 11
  • [ 7752-72-9 ]
  • C19H16ClF3N4O [ No CAS ]
  • 12
  • [ 7752-72-9 ]
  • C19H15Cl3F2N4O [ No CAS ]
  • 13
  • [ 7752-72-9 ]
  • C19H20ClN5O3 [ No CAS ]
  • 14
  • [ 7752-72-9 ]
  • C19H16ClF3N4O*ClH [ No CAS ]
  • 15
  • [ 7752-72-9 ]
  • C20H17ClF3N3O [ No CAS ]
  • 16
  • [ 7752-72-9 ]
  • C19H15Cl3N4O3 [ No CAS ]
  • 17
  • [ 7752-72-9 ]
  • 5-chloro-N-(2-(6-(4-chlorophenoxy)pyridin-3-yl)ethyl)-6-methylpyrimidin-4-amine [ No CAS ]
  • 18
  • [ 7752-72-9 ]
  • 4-(2-(5-chloro-6-methylpyrimidin-4-ylamino)ethyl)phenol [ No CAS ]
  • 19
  • [ 7752-72-9 ]
  • C19H18Cl2N4 [ No CAS ]
  • 20
  • [ 7752-72-9 ]
  • C18H20ClN5S [ No CAS ]
  • 21
  • 4-(chloromethyl)-1-(4-methylphenyl)-1H-pyrazole [ No CAS ]
  • [ 7752-72-9 ]
  • C16H15ClN4O [ No CAS ]
YieldReaction ConditionsOperation in experiment
70.6% With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; Take 0.15g (0.001mol) 4- hydroxy-5-chloro-6-methylpyrimidine, 0.21g (0.001mol) 4- chloro-1- (4-methylphenyl) lH-pyrazole, 0.14 g (0.001mol) of potassium carbonate in 50ml single neck flask, 10mlN, N- dimethylformamide as a solvent, was heated to 100 deg.] C, the reaction 4-10 hours, monitored by TLC after completion of the reaction, the solvent was distilled off under reduced pressure, was added ( 3 × 50ml) and extracted with ethyl acetate, the organic phase was washed with saturated brine 50ml, after solvent removal the residue by column chromatography (eluent, ethyl acetate and petroleum ether, the volume ratio of 1: 2) to give a white solid 0.22g yield 70.6%
  • 22
  • formimidamide acetate [ No CAS ]
  • [ 609-15-4 ]
  • [ 7752-72-9 ]
YieldReaction ConditionsOperation in experiment
66% With sodium methylate; In methanol; at 20℃; A solution of 8.80 g (0.16 mol) of CH3ONa in methanol was added slowly to a solution of 11.30 g (0.11 mol) of formimidamide acetate in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 h after addition at room temperature. Followed by addition of 11.17 g (0.068 mol) of ethyl 2-chloro-3-oxobutanoate, the mixture was continued stirring for another 5-7 h at room temperature. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HCl, and then filtered to afford orange-yellow solid, the water phase was extracted with ethyl acetate (3×50 mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was dissolved to 50 ml of ethyl acetate, stand overnight to obtain 6.48 g as orange-yellow solid with yield of 66%. m.p. 181184 C.
  • 23
  • [ 7752-72-9 ]
  • C20H20ClN3O [ No CAS ]
  • 24
  • [ 7752-72-9 ]
  • C19H18Cl2N4O [ No CAS ]
  • 25
  • [ 7752-72-9 ]
  • C17H16Cl2N4OS [ No CAS ]
  • 26
  • [ 7752-72-9 ]
  • C16H15Cl2N5O [ No CAS ]
  • 27
  • [ 7752-72-9 ]
  • 5‐chloro‐6‐methyl‐N‐(4‐(p‐tolyloxy)benzyl)pyrimidin‐4‐amine [ No CAS ]
  • 28
  • [ 7752-72-9 ]
  • C18H21ClF3N5O [ No CAS ]
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

Related Functional Groups of
[ 7752-72-9 ]

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Related Parent Nucleus of
[ 7752-72-9 ]

Pyrimidines

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