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Chemical Structure| 3122-84-7 Chemical Structure| 3122-84-7

Structure of 3122-84-7

Chemical Structure| 3122-84-7

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Product Details of [ 3122-84-7 ]

CAS No. :3122-84-7
Formula : C6H7ClN2O
M.W : 158.59
SMILES Code : COCC1=CC(Cl)=NC=N1
English Name :4-Chloro-6-(methoxymethyl)pyrimidine
MDL No. :MFCD16707817
InChI Key :QOOQUMTZWQEHTR-UHFFFAOYSA-N
Pubchem ID :14306171

Safety of [ 3122-84-7 ]

Application In Synthesis of [ 3122-84-7 ]

* 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 [ 3122-84-7 ]

[ 3122-84-7 ] Synthesis Path-Downstream   1~14

YieldReaction ConditionsOperation in experiment
entspr. Keton, POCl3;
  • 2
  • [ 157637-71-3 ]
  • [ 3122-84-7 ]
  • [ 921604-60-6 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In N,N-dimethyl-formamide at 80℃;
  • 3
  • [ 3122-78-9 ]
  • [ 3122-84-7 ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: 4-methoxymethyl-6-hydroxypyrimidine With trichlorophosphate In dichloromethane at 20℃; for 18h; Stage #2: With water; sodium hydroxide In water 218.B Step B: 4-Chloro-6-(methoxymethyl)pyrimidine 6-(Methoxymethyl)pyrimidin-4-ol (1.38 g, 9.85 mmol) was taken up in dichloromethane (14 ml) and phosphorous oxychloride (9 mL, 97 mmol) was added at ambient temperature. The mixture was stirred at ambient for 18 h and concentrated. The residue was taken up in ice-water and the pH was adjusted to 7 with 1N sodium hydroxide. The mixture was extracted with chloroform and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (5-10% ethyl acetate/chloroform) to afford 4-chloro-6-(methoxymethyl)pyrimidine (1.2 g, 7.57 mmol, 77% yield) as a pale yellow oil, which solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 8.88 (1H, d, J=1.01 Hz), 7.52 (1H, d, J=1.01 Hz), 4.53 (2H, s), 3.50 (3H, s). MS (LC/MS) R.T.=0.98; [M+H]+=159.10.
77% Stage #1: 4-methoxymethyl-6-hydroxypyrimidine With trichlorophosphate In dichloromethane at 20℃; for 18h; Stage #2: With sodium hydroxide In water 218.B Step B: 4-Chloro-6-(methoxymethyl)pyrimidine6-(Methoxymethyl)pyrimidin-4-ol (1.38 g, 9.85 mmol) was taken up in dichloromethane (14 ml) and phosphorous oxy chloride (9 mL, 97 mmol) was added at ambient temperature. The mixture was stirred at ambient for 18 h andconcentrated. The residue was taken up in ice-water and the pH was adjusted to 7 with IN sodium hydroxide. The mixture was extracted with chloroform and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (5 -10 % ethyl acetate/chloroform) to afford 4-chloro-6- (methoxymethyl)pyrimidine (1.2 g, 7.57 mmol, 77 % yield) as a pale yellow oil, which solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 8.88 (1 H, d, J=1.01 Hz), 7.52 (1 H, d, J=1.01 Hz), 4.53 (2 H, s), 3.50 (3 H, s). MS (LC/MS) R.T. = 0.98; [M+H]+ = 159.10.
77% With trichlorophosphate In dichloromethane at 20℃; for 18h; 218.B Step B: 4-Chloro-6-(methoxymethyl)pyrimidine 6-(Methoxymethyl)pyrimidin-4-01 (1.38 g, 9.85mmol) was taken up in dichloromethane (14 ml) and phosphorousoxychloride (9 ml., 97 mmol) was added at ambienttemperature. The mixture was stirred at ambient for 18 handconcentrated. The residue was taken up in ice-water and thepH was adjusted to 7 with IN sodium hydroxide. The mixturewas extracted with chloroform and dried over sodium sulfate,filtered and concentrated in vacuo. The residue was purifiedby colunm chromatography (5-10% ethyl acetate/chloroform)to afford 4-chloro-6-(methoxymethyl)pyrimidine (1.2g, 7.57 mmol, 77% yield) as a pale yellow oil, which solidified on standing.
In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane 4-Chloro-6-(methoxymethyl)pyrimidine (24-3) 4-Chloro-6-(methoxymethyl)pyrimidine (24-3) 6-(Methoxymethyl)pyrimidin-4-ol (948 mg, 6.8 mmole) was taken up in CH2Cl2 (10 mL) and POCl3 (6 mL) at room temperature. After 18 hours, the mixture was concentrated to dryness. The residue was taken up in ice water and the pH adjusted to 7. The mixture was extracted with CHCl3 (4*). The combined organic layers were dried (MgSO4), filtered, and concentrated to give the title compound which was sufficiently pure for use in the next step without purification. 1H-NMR (500 MHz, CDCl3) δ8.95 (s, 1 H), 7.58 (s, 1 H), 4.48 (s, 2 H), 3.50 (s, 3 H).
In trichlorophosphate 25.b 2-(6-Morpholino-4-pyrimidinylmethylsulfinyl)-1H-thieno[3,4-d]imidazole (b) 50 g of 6-hydroxy-4-methoxymethylpyrimidine were heated in 375 ml of phosphorus oxychloride until a clear solution had been produced. The excess phosphorus oxychloride was removed by distillation in vacuo, and the residue was poured into ice-water. Extraction with dichloromethane and drying over sodium sulfate were followed by concentration of the solution in vacuo. 58 g of 6-chloro-4-methoxymethylpyrimidine were obtained as an oil which was used without further purification in the next stage.
18.ii Preparation of 5-methoxy-2-(6-piperidino-4-pyrimidinylmethylthio)-(1H)-benzimidazole (ii) Substituting 4-methoxymethyl-6-hydroxypyrimidine (15.40 g) for 4-methoxymethyl-5-methyl-6-hydroxypyrimidine and using corresponding molar proportions of the other reagents in the method of Example 10(ii), gave 4-methoxymethyl-6-chloropyrimidine, 16.77 g, m.p. 34°-36°. It was used without further purification.
Stage #1: 4-methoxymethyl-6-hydroxypyrimidine With trichlorophosphate for 2h; Heating / reflux; Stage #2: With ammonia 501.B [0531] The mixture of compound 501A (5.3 g, 37.8 mmol.) and POCl3 (40 mL) was heated to reflux for 2.0 hrs. Concentration in vacuo and the residue was poured into a mixture of ice-CH2Cl2. The pH was adjusted to 6.5 to 7 using concentrated NH4OH. The mixture was extracted with CH2Cl2 (×3) and combined extracts were dried over Na2SO4. Concentration in vacuo followed by flash chromatography (CH2Cl2-EtOAc: 9:1) on silica gel gave 5.33 g of compound 501B as a pale yellow oil.

  • 4
  • [ 3122-84-7 ]
  • [ 302964-09-6 ]
YieldReaction ConditionsOperation in experiment
48% With ammonium hydroxide for 3h; 218.C Step C: 6-(Methoxymethyl)pyrimidin-4-amine A mixture of 4-chloro-6-(methoxymethyl)pyrimidine (1.2 g, 7.57 mmol) and ammonium hydroxide (20 ml) was heated in a sealed tube for 3 hours. The mixture was cooled to ambient temperature and concentrated. The residue was triturated with ether to afford 6-(methoxymethyl)pyrimidin-4-amine (0.50 g, 3.59 mmol, 48% yield) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.47 (1H, s), 6.55 (1H, s), 5.12 (2H, br. s.), 4.38 (2H, s), 3.45 (3H, s). MS (LC/MS) R.T.=0.42; [M+H]+=140.20.
48% With ammonium hydroxide for 3h; Sealed tube; 218.C Step C: 6-(methoxymethyl)pyrimidin-4-amine A mixture of 4-chloro-6-(methoxymethyl)pyrimidine (1.2 g, 7.57 mmol) and ammonium hydroxide (20 ml) was heated in a sealed tube for 3 hours. The mixture was cooled to ambient temperature and concentrated. The residue was triturated with ether to afford 6-(methoxymethyl)pyrimidin-4-amine (0.50 g, 3.59 mmol, 48 % yield) as a pale yellow solid. XH NMR (400 MHz, CDCl3) δ ppm 8.47 (1 H, s), 6.55 (1 H, s), 5.12 (2 H, br. s.), 4.38 (2 H, s), 3.45 (3 H, s). MS (LC/MS) R.T. = 0.42; [M+H]+ = 140.20.
48% With ammonium hydroxide for 3h; Sealed tube; 218.C Step C: 6-(Methoxymethyl)pyrimidin-4-amine A mixture of 4-chloro-6-(methoxymethyl)pyrimidine(1.2 g, 7.57 mmol) and ammonium hydroxide (20 ml) was heated in a sealed tube for 3 hours. The mixture was cooled to ambient temperature and concentrated. The residuewas triturated with ether to afford 6-(methoxymethyl)pyrimidin-4-amine (0.50 g, 3.59 mmol, 48% yield) as a pale yellows olid.
With ammonia at 85℃; for 3h; 501.C [0532] The mixture of compound 501B (3.2 g, 20 mmol.) and NH4OH (50 mL) was heated to 85.C in a pressure tube for 3.o hrs. After cooled to room temperature, the reaction mixture was concentrated in vacuo and the residue was triturated with ether to give 2.81 g of compound 501C as a pale yellow solid.

  • 5
  • [ 4248-19-5 ]
  • [ 3122-84-7 ]
  • [ 436851-93-3 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In 1,4-dioxane tert-Butyl 6-(methoxymethyl)pyrimidin-4-ylcarbamate (24-4) tert-Butyl 6-(methoxymethyl)pyrimidin-4-ylcarbamate (24-4) To a solution of 4-chloro-6-(methoxymethyl)pyrimidine (768 mg, 4.84 mmole) in dry dioxane (10 mL) was added Cs2CO3 (2.37 g, 7.26 mmole), Xanthphos (84 mg, 0.15 mmole), Pd2(dba)3 (44 mg, 0.05 mmole), and tert-butylcarbamate (681 mg, 5.81 mmole) then the mixture was heated to reflux. After 3 hours, the mixture was cooled to room temperature, diluted with H20, and extracted with CH2Cl2 (3*). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (35% EtOAc/hexanes) gave the title compound as a pale yellow solid. 1H-NMR (500 MHz, CDCl3) δ8.74 (s, 1 H), 8.04 (s, 1 H), 8.00 (bs, 1 H), 4.51 (s, 2 H), 3.51 (s, 3 H), 1.55 (s, 9 H).
  • 6
  • [ 110-91-8 ]
  • [ 3122-84-7 ]
  • [ 121242-67-9 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran 25.c 2-(6-Morpholino-4-pyrimidinylmethylsulfinyl)-1H-thieno[3,4-d]imidazole (c) 29 g of 6-chloro-4-methoxymethylpyrimidine were dissolved in 200 ml of tetrahydrofuran, and 32 g of morpholine were added. After 3 hours at room temperature, the mixture was filtered with suction, and the filtrate was concentrated in vacuo. 37 g of 6-morpholino-4-methoxymethylpyrimidine were obtained (melting point 56° C.).
  • 7
  • [ 3122-84-7 ]
  • [ 118779-94-5 ]
YieldReaction ConditionsOperation in experiment
18.iii Preparation of 5-methoxy-2-(6-piperidino-4-pyrimidinylmethylthio)-(1H)-benzimidazole (iii) Substituting 4-methoxymethyl-6-chloropyrimidine (4.0 g) for 4-methoxymethyl-5-methyl-6-chloropyrimidine and using corresponding molar proportions of the other reagents in the method of Example 10(iii) gave 4-methoxymethyl-6-piperidino-pyrimidine, 4,88 g, as an oil. It was used without further purification.
  • 8
  • [ 3122-84-7 ]
  • [ 118780-00-0 ]
YieldReaction ConditionsOperation in experiment
22.i Preparation of 5-methoxy-2-(6-dimethylamino-4-pyrimidinylmethylthio)-(1H)-benzimidazole (i) Substituting 4-methoxymethyl-6-chloropyrimidine (4.0 g) for 2-methoxymethyl-4-chloropyrimidine, and using corresponding molar proportions of the other reagents, in the method of Example 8(i), gave 4-methoxymethyl-6-dimethylaminopyrimidine, 4.1 g, as a low melting solid, m.p. 42°-44°. It was used without further purification.
  • 9
  • [ 90162-13-3 ]
  • [ 3122-84-7 ]
  • [ 65934-74-9 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate In 1-methyl-pyrrolidin-2-one at 90℃; for 4h; 18C.1 A suspension of 3.4 g (16.8 mMol) 6-hydroxy-naphthalene-i-carboxylic acid methyl ester (see Step 3.1), 3.2 g (20.2 mMol) 4-chloro-6-(methoxymethyl)pyrimidine (preparation see: BE 64 1253, p.38; or WO 2002 / 45652, p.102) and 7.85 g (37 mMol) K3PO4 in 85 ml NMP is stirred for 4 h at 90 0C. The cooled mixture is diluted with 0.4 I EtOAc and 0.4 I water, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed twice with water and brine, dried (Na2SO4) and concentrated. Chromatography (SiO2; CH2CI2/Et0Ac 19:1 → 9:1 → 4:1) gives the title compound: m.p.: 87-88 0C; MS: [M+1]+ = 325; TLC(CH2CI2/EtOAc 4:1): Rf = 0.28.
  • 10
  • [ 3122-84-7 ]
  • [ 1192813-77-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ammonium hydroxide / 3 h / Sealed tube 2: dichloromethane / 18 h / 20 °C
Multi-step reaction with 2 steps 1: ammonium hydroxide / 3 h / Sealed tube 2: dichloromethane / 18 h / 20 °C
  • 11
  • [ 1422383-11-6 ]
  • [ 76-05-1 ]
  • [ 3122-84-7 ]
  • [ 1422383-90-1 ]
YieldReaction ConditionsOperation in experiment
33% Stage #1: N-[(10R,14S)-5-amino-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-14-yl]-1-(3-chloro-2-fluorophenyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide dihydrochloride; 4-chloro-6-(methoxymethyl)pyrimidine With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 150℃; for 0.5h; Microwave irradiation; Stage #2: trifluoroacetic acid In water; acetonitrile 149 [00609] Example 149. l-(3-Chloro-2-fluorophenyl)-N-[(10R,14S)-5-[6- (methoxymethyl)pyrimidin-4-yl]amino} - 10-methyl-9-oxo-8, 16- diazatricyclo[13.3.1.02'7]nonadeca-l(19),2(7),3,5,15,17-hexaen-14-yl]-5-methyl-lH- l,2,3-triazole-4-carboxamide, TFA salt: The solution of Example 89 (Alternative, HCl salt) (0.01 g, 0.016 mmol), 4-chloro-6-(methoxymethyl)pyrimidine (7.66 mg, 0.048 mmol), and DIPEA (0.014 mL, 0.081 mmol) in IPA (0.5 mL) was heated at 150 °C for 30 min under microwave conditions. The reaction was cooled to rt and concentrated. The residue was purified by reverse phase to yield the desired product (5 mg, 33%) as a yellow solid. 1H NMR (500 MHz, MeOD) δ 8.80 (d, J = 0.8 Hz, 1H), 8.76 (d, J = 5.8 Hz, 1H), 8.06 (d, J = 1.1 Hz, 1H), 7.84 - 7.73 (m, 5H), 7.56 (ddd, J = 8.0, 6.5, 1.7 Hz, 1H), 7.46 (td, J = 8.1, 1.4 Hz, 1H), 7.04 (d, J = 0.8 Hz, 1H), 5.35 (dd, J = 11.1, 5.9 Hz, 1H), 4.58 (d, J = 0.6 Hz, 2H), 3.53 (s, 3H), 2.80 - 2.73 (m, 1H), 2.44 (d, J = 0.8 Hz, 3H), 2.26 - 2.17 (m, 1H), 2.02 - 1.90 (m, 2H), 1.64 - 1.47 (m, 2H), 0.97 (d, J = 6.9 Hz, 3H), 0.55 - 0.45 (m, 1H) ppm. MS(ESI) m/z: 670.3 (M+H)+. Analytical HPLC RT = 4.94 min (Method A).
  • 12
  • [ 95-76-1 ]
  • [ 3122-84-7 ]
  • [ 1428558-37-5 ]
YieldReaction ConditionsOperation in experiment
57% In 1,4-dioxane at 100℃; for 54h; 95 N-(3,4-dichlorophenyl)-6-(methoxymethyl)pyrimidin-4-amine N-(3,4-dichlorophenyl)-6-(methoxymethyl)pyrimidin-4-amine A mixture of 3,4-dichloroaniline (1.328 g, 8.20 mmol) and 4-chloro-6-(methoxymethyl)pyrimidine (0.65 g, 4.10 mmol) in dioxane (20.5 ml) was heated at 100° C. for 54 h, cooled to room temperature and concentrated onto Na2SO4. The residue was purified on silica gel using 50-100% ethyl acetate in hexanes, then 10-15% methanol in ethyl acetate. The desired fractions were concentrated to give a dark brown solid which was triturated with DCM to yield N-(3,4-dichlorophenyl)-6-(methoxymethyl)pyrimidin-4-amine as a brown solid (0.66 g, 57%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.67 (1H, d, J=1.00 Hz), 7.69 (1H, d, J=2.51 Hz), 7.44 (1H, d, J=8.53 Hz), 7.29 (1H, dd, J=8.53, 2.51 Hz), 6.95 (1H, br. s.), 6.81 (1H, d, J=1.00 Hz), 4.45 (1H, d, J=0.50 Hz), 3.50 (2H, s). LCMS: R.T.=0.77; [M+H]+=283.98.
  • 13
  • [ 95-76-1 ]
  • [ 3122-84-7 ]
  • [ 1428558-38-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1,4-dioxane / 54 h / 100 °C 2: boron tribromide / dichloromethane / 0.5 h / 0 °C
  • 14
  • [ 41051-15-4 ]
  • [ 3122-84-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium methylate / 18 h / Reflux 2: trichlorophosphate / dichloromethane / 18 h / 20 °C
 

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