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Chemical Structure| 1074-40-4 Chemical Structure| 1074-40-4

Structure of 1074-40-4

Chemical Structure| 1074-40-4

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Product Details of [ 1074-40-4 ]

CAS No. :1074-40-4
Formula : C5H4Cl2N2O
M.W : 179.00
SMILES Code : COC1=NC(Cl)=CC(Cl)=N1
MDL No. :MFCD03428360
InChI Key :WDELVDLDINRUQF-UHFFFAOYSA-N
Pubchem ID :12052160

Safety of [ 1074-40-4 ]

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

Computational Chemistry of [ 1074-40-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 38.54
TPSA ?

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

35.01 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

2.43
Log Po/w (WLOGP)?

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

1.79
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.

0.95
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

2.21
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.9

Water Solubility

Log S (ESOL):?

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

-2.86
Solubility 0.248 mg/ml ; 0.00138 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.

-2.81
Solubility 0.279 mg/ml ; 0.00156 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

-3.01
Solubility 0.175 mg/ml ; 0.000975 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

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.

-5.67 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)

1.91

Application In Synthesis of [ 1074-40-4 ]

* 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 [ 1074-40-4 ]

[ 1074-40-4 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 123-00-2 ]
  • [ 1074-40-4 ]
  • [ 104665-82-9 ]
  • 2
  • [ 124-41-4 ]
  • [ 1074-40-4 ]
  • [ 6320-15-6 ]
  • 3
  • [ 75053-80-4 ]
  • [ 1074-40-4 ]
  • 4-chloro-2-methoxy-6-[4-(3-trifluoromethyl-phenoxy)-phenoxy]-pyrimidine [ No CAS ]
  • 4
  • [ 1074-40-4 ]
  • [ 5188-07-8 ]
  • 4-chloro-2-methoxy-6-methylsulfanyl-pyrimidine [ No CAS ]
  • 7
  • [ 52516-13-9 ]
  • [ 1074-40-4 ]
  • [ 1016644-41-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In ethanol; at 80.0℃; for 3.0h; Step 1: A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (0.7 g), 2,4-dichlorophenethylamine (0.82 g) and sodium bicarbonate (0.88 g) in ethanol (25 mL) is heated at 80° C. for three hours and poured into water (400 mL). The resulting solid is filtered and air dried to afford (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine.
With sodium carbonate; In ethanol; at 80.0℃; for 3.0h; Eurphile I;I- 16-[2-(2.4-DkhIoiO-rhohgHVJ >-ethvS3iJiino|-2-me.hyi-pymidir;-4-yl j-rhoyrrhpsiine-3-alphaifboxyJsc ^cidSic|> . : lambda .sohpiion of 4,6-dich]uro-2-rskappalhoxypyrirHfdine (0,7 g_J, 2-f2,4-dichloro-phelambdayi'}-e.hykitaunipie (0,74 g) and Na>COj (0.88 gs hi EfOH (25 mU is heated at 80"C for 3 hours and poured nio wafer (400 nttj. The resulting solid is filtered and air dried to afford (6<MQro-2-02e.hpsixchi^ggammaj.g^
  • 8
  • [ 1074-40-4 ]
  • 2-methoxy-4-methylsulfanyl-6-[4-(3-trifluoromethyl-phenoxy)-phenoxy]-pyrimidine [ No CAS ]
  • 9
  • [ 2975-41-9 ]
  • [ 1074-40-4 ]
  • [ 885068-85-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In ethanol;Heating / reflux; 83(a)Step 1. A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (1 g, 5.59 mmol), 2-aminoindan (0.72 mL, 5.59 mmol) and sodium bicarbonate (0.7 g, 8.38 mmol) in EtOH (25 mL) is refluxed overnight. The reaction is cooled to room temperature, quenched with water (100 mL) and stirred for one hour. The formed precipitate is suction filtered and air dried to afford (6-chloro-2-methoxy-pyrimidin-4-ylV indan-1-yl-amine (1.5 g). LCMS: R? = 3.35 minutes, LCMS: 276, 278 (M+H).
With sodium hydrogencarbonate; In ethanol;Heating / reflux; solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (1 g, 5.59 mmol), 2-aminoindan (0.72 mL, 5.59 mmol) and sodium bicarbonate (0.7 g, 8.38 mmol) in EtOH (25 mL) is refluxed overnight. The reaction is cooled to room temperature, quenched with water (100 mL) and stirred for one hour. The formed precipitate is suction filtered and air dried to afford (6-chloro-2-methoxy-pyrimidin-4-yl)- indan-1-yl-amine (1.5 g). LCMS: Rtau = 3.35 minutes, LCMS: 276, 278 (M+H).
  • 10
  • [ 55601-21-3 ]
  • [ 1074-40-4 ]
  • [ 885068-32-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In ethanol; at 85.0℃; for 5.0h;Heating / reflux; Step 4. A mixture of <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (0.66 g, 3.69 mmol), 2,2-difluoro-2-phenyl- ethylamine (0.58 g, 3.69 mmol), and NaHCO3 (0.93 g, 11.1 mmol) in 95percent EtOH (10 mL) is heated to reflux. After stirred at 85°C for 5 h. The mixture is diluted with water, filtered, washed (water), and dried to afford (6-chloro-2-methoxy-pyrimidin-4-ylV(2.2-difluoro-2-phenyl-ethyl)-amine as a solid (0.58 g). LCMS: RT = 3.17 minutes, MS: 300 (M+H). 1H NMR (300 MHz, CDCl3) ? 7.57-7.45 (5H, m), 6.1 (IH, s), 5.2 (IH, s), 4.2-4 (2H, m), 3.92 (3H, s).
With sodium hydrogencarbonate; In ethanol; at 85.0℃; for 5.0h;Heating / reflux; A mixture of <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (0,66 g, 3.69 mmol), 2,2-difluoro-2-phenyl- ethylamine (0.58 g, 3.69 mmol), and NaHCO3 (0.93 g, 11.1 mmol) in 95percent EtOH (10 mL) is heated to reflux. After stirred at 850C for 5 h. The mixture is diluted with water, filtered, washed (water), and dried to afford (6-cMoro-2-methoxy-pyrimidm-4-yl)-(2,2-difluoro-2-phenyl-ethyl)-amine as a solid (0.58 g). LCMS: RT = 3.17 minutes, MS: 300 (M+H). 1H NMR (300 MHz, CDCl3) delta 7.57-7.45 (5H, m), 6.1 (IH, s), 5.2 (IH, s), 4.2-4 (2H, m), 3.92 (3H, s).
  • 11
  • [ 220362-31-2 ]
  • [ 1074-40-4 ]
  • [ 885068-39-3 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In ethanol; at 80.0℃; for 3.0h; Step 3. A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (0.7 g), 2-(3,4-difluoro-phenyl)-ethylamine (0.66 g) and sodiumbicarbonate (0.88 g) in EtOH (25 mL) is heated at 8O0C for three hours, poured into water (400 mL) and the solid is filtered and air dried to afford (6-chloro-2-methoxy-pyrimidin-4- ylVr2-(3.4-difluoro-phenylVethvll-amine (1.1 g). MS: 312 (M+H); 1H NMR (300 MHz, CDCl3) ? 6.9- 7 (3H, m); 6.05 (lH,s); 3.95 (3H, s); 3.6-3.7 (2H, m); 2.95 (2H, t).
With sodium hydrogencarbonate; In ethanol; at 80.0℃; for 3.0h; A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (0.7 g), 2-(3,4-difluoro-phenyl)-ethylamine (0.66 g) and sodiumbicarbonate (0.88 g) in EtOH (25 mL) is heated at 8O0C for three hours, poured into water (400 mL) and the solid is filtered and air dried to afford (6-chloro-2-methoxy-pyrimidin-4- viyr2-f3.4-difluoro-phenvD-ethyl1 -amine (1.1 g). MS: 312 (M+H); 1H NMR (300 MHz, CDCl3) delta 6.9- 7 (3H, m); 6.05 (lH,s); 3.95 (3H, s); 3.6-3.7 (2H, m); 2.95 (2H, t).
  • 12
  • [ 458-40-2 ]
  • [ 1074-40-4 ]
  • [ 885066-01-3 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In ethanol; at 80.0℃; for 3.0h; Step 3. A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> [0.7 g, Intermediate (4)], 2-(3-fluoro-4- methoxy-phenyl)-ethylamine [0.66 g, Intermediate (3)] and sodium bicarbonate (0.88 g) in EtOH (25 mL) is heated at 800C for three hours and poured into water (400 mL). The resulting solid is filtered and air dried affording (6-chloro-2-methoxy-pyrimidin-4-ylVr2-(3-fluoro-4-methoxyphenyl)- ethyllamine [1.1 g, Intermediate (5)]. MS: 312 (M+H); 1H NMR (CDCl3): ? 6.9-7 (3H, m); 6.05 (IH, s); 3.95 (3H, s); 3.85 (3H, s); 3.6-3.7 (2H, m); 2.95 (2H, t).
With sodium hydrogencarbonate; In ethanol; at 80.0℃; for 3.0h; A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> [0.7 g, Intermediate (4)], 2-(3-fluoro-4- methoxy-phenyl)-ethylamine [0.66 g, Intermediate (3)] and sodium bicarbonate (0.88 g) in EtOH (25 mL) is heated at 8O0C for three hours and poured into water (400 mL). The resulting solid is filtered and air dried affording (6-cMoro-2-methoxy-pyrimidin-4-yl)-f2-(3-fluoro-4-methoxyphenyl)- ethyliamine [1.1 g, Intermediate (5)]. MS: 312 (M+H); 1H NMR (CDCl3): delta 6.9-7 (3H, m); 6.05 (IH, s); 3.95 (3H1 s); 3.85 (3H, s); 3.6-3.7 (2H, m); 2.95 (2H, t).
  • 13
  • [ 156-41-2 ]
  • [ 1074-40-4 ]
  • [ 885067-45-8 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In ethanol; at 80.0℃; for 3.0h; 35(n)Step 1. A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> [0.7 g, Intermediate (4)], 2-(4-chlorophenyl)- ethylamine (0.66 g) and sodium bicarbonate (0.88g) in EtOH (25 ml) is heated at 80°C for three hours, poured into water (400 mL) and the solid is filtered and air dried affording (6-chloro-2-methoxy- pyrimidin-4-yl)-[2-(4-chlorophenyl)-ethyl]amine [1.1 g, Intermediate (14)]. MS: 299 (M+H). 1H NMR (CDs)2SO]: ? 8 (d, 2H, J=3 Hz); 7.4 (2H, d, J=3 Hz); 6.05 (IH, s); 4 (3H3 s): 3.6-3.7 (2H, m); 2.95 (2H, t).
With sodium hydrogencarbonate; In ethanol; at 80.0℃; for 3.0h; A solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> [0.7 g, Intermediate (4)], 2-(4-chlorophenyl)- ethylamine (0.66 g) and sodium bicarbonate (O.88g) in EtOH (25 ml) is heated at 8O0C for three hours, poured into water (400 mL) and the solid is filtered and air dried affording (6-chloro-2-methoxy- pyrimidin-4-yl)-[2-(4-chlorophenyl)-ethyl]amine [1.1 g, Intermediate (14)]. MS: 299 (M+H). 1H NMR (CD3)2SO]: delta 8 (d, 2H, J=3 Hz); 7.4 (2H1 d, J=3 Hz); 6.05 (IH, s); 4 (3H, s): 3.6-3.7 (2H1 m); 2.95 (2H, t).
  • 14
  • [ 156-41-2 ]
  • [ 1074-40-4 ]
  • 3-{6-[2-(4-chloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid hydrochloride [ No CAS ]
  • 15
  • [ 885067-88-9 ]
  • [ 1074-40-4 ]
  • [ 885067-89-0 ]
YieldReaction ConditionsOperation in experiment
79% With sodium hydrogencarbonate; In ethanol; for 4.0h;Heating / reflux; Step 3. To a solution of <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (0.606 g, 3.38 mmol, Intermediate (4)] and 2-(2,2-difluoro-benzo[l,3]dioxol-5-yl)-ethylamine hydrochloride (0.884 g, 3.72 mmol, Intermediate (62)]) in EtOH (11 mL) is added sodium bicarbonate (0.85 g, 10.14 mmol) and heated to reflux for 4 hours. The reaction mixture is filtered and filtrate is concentrated, residue solid is washed with small amount of EtOH to yield (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2.2-difluoro- benzori.31dioxol-5vn-ethyl]-amine [0.918 g, 79percent, Intermediate (63)] as a solid. LC/MS: MS: 344 (M+H).
79% With sodium hydrogencarbonate; In ethanol; for 4.0h;Heating / reflux; To a solution of <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (0.606 g, 3.38 mmol, Intermediate (4)] and 2-(2,2-difluoro-benzo[l,3]dioxol-5-yl)-ethylamine hydrochloride (0.884 g, 3.72 mmol, Intermediate (62)]) in EtOH (11 mL) is added sodium bicarbonate (0.85 g, 10.14 mmol) and heated to reflux for 4 hours. The reaction mixture is filtered and filtrate is concentrated, residue solid is washed with small amount of EtOH to yield (6-chloro-2-methoxy-pyrimidin-4-yl')-[2-(2,2-difluoro- benzo[l ,31dioxol-5ylVethyll-amine [0.918 g, 79percent, Intermediate (63)] as a solid. LC/MS: MS: 344 (M+H).
  • 16
  • [ 885068-05-3 ]
  • [ 1074-40-4 ]
  • [ 885068-04-2 ]
YieldReaction ConditionsOperation in experiment
76% With sodium hydrogencarbonate; In ethanol; for 5.0h;Heating / reflux; This compound (1.8 g, 8.7 mmol) is dissolved in EtOH (25 mL) and treated with <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> [1.3 g, 7.25 mmol, Intermediate (4)] and sodium bicarbonate (1.52 g, 18.13 mmol). The mixture is heated to reflux for 5 hours. Solid is filtered and EtOH is removed in vacuo. The residue is washed with small amount of DCM to obtain (6-chloro- 2-me1hoxy-pyrimidin-4-yl)-[2-(2-fluoro-4-trifluoromethyl-phenyl)-ethyl]-amine (2.59 g, 76percent) as a solid. LC/MS: 350 (M+H).
76% With sodium hydrogencarbonate; In ethanol; for 5.0h;Heating / reflux; 2-Fluoro-4-trifluoromethyl-phenyl acetonitrile (2 g, 9.85 mmol) is hydrogenated with H2 in a balloon, 10percent Pd/C (522 mg, 5 molpercent) in 95percent EtOH (50 mL) containing concentrated hydrochloric acid (1.64 mL) at room temperature for 15 hours. The mixture is filtered and filtrate is concentrated to a solid that is washed with diethyl ether to obtain 2-(2-fluoro-4-trifluoromethyl-phenyl)-ethylamine hydrochloride (1.88 g, 78percent) as a solid. LC/MS: 208 (M+H). This compound (1.8 g, 8.7 mmol) is dissolved in EtOH (25 mL) and treated with <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> [1.3 g, 7.25 mmol, Intermediate (4)] and sodium bicarbonate (1.52 g, 18.13 mmol). The mixture is heated to reflux for 5 hours. Solid is filtered and EtOH is removed in vacuo. The residue is washed with small amount of DCM to obtain (6-chloro- 2-methoxyphiyrimidm-4-yl)-[2-r2-fluoro-44rifluoromethylphihenyl)-ethyl1-amine (2.59 g, 76percent) as a solid. LC/MS: 350 (M+H).
  • 17
  • C-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-yl)-methylamine [ No CAS ]
  • [ 1074-40-4 ]
  • [ 885069-11-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In ethanol; for 5.0h;Heating / reflux; 92 Step 1. A mixture of <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (0.27 g, 1.48 mmol), C-(4-methyl-3,4- dihydro-2H-benzo[l,4]oxazin-2-yl)-methylamine (0.22 g, 1.23 mmol), and NaHCO3 (0.62 g, 7.4 mmol) in EtOH (7 mL) is heated to reflux for 5 h. The mixture is concentrated in vacuo. The residue is partitioned between EtOAc and water, and extracted with EtOAc. The extracts are dried (Na2SO4), and concentrated to afford ('6-chloro-2-methoxy-pyrimidin-4-yl)-(4-methyl-314-dihydro-2H- benzof 1.41oxazin-2-ylmethylVamine (0.39 g). LCMS: R? = 3.27 minutes; MS: 321 (M+H).
  • 18
  • [ 1758-98-1 ]
  • [ 1074-40-4 ]
YieldReaction ConditionsOperation in experiment
44% With trichlorophosphate; for 4.0h;Heating / reflux; Step 2; 4,6-dichloro-2-methoxy-pyrimidine; 2-Methoxy-pyrimidine-4,6-diol was dissolved in phosphorous oxychloride and the resultant reaction mixture was refluxed for four hours. After quenching with basic ice-water, the resultant aqueous mixture was extracted with ethyl acetate and the combined extracts dried <n="52"/>over magnesium sulfate. The organics were concentrated in vacuo yielding 1.1 g (44percent, crude yield) of the title compound.LCMS: Mass Found (M+l, 179)
14% Step 2: 4,6-dichloro-2-methoxypyrimidine; 2.25 g (7.92 mmol) 2-methoxypyrimidine-4,6-diol and 10.0 mL (108.92 mmol) phosphorus oxychloride were boiled for 2 h. The reaction mixture was poured onto alkaline ice water and made alkaline with NaOH. The aqueous phase was extracted with DCM. The organic phase was separated off, dried and evaporated down i.vac.Yield: 0.20 g (14percent of theory)ESI-MS: m/z=179 (M+H)+ Rt(HPLC): 1.38 min (method B)
  • 19
  • [ 1074-40-4 ]
  • [ 941317-84-6 ]
YieldReaction ConditionsOperation in experiment
39% With potassium carbonate; hydrazine; In tetrahydrofuran; for 72.0h; Step 3; (6-Chloro-2-methoxy-pyrimidin-4-yl) hydrazine; <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (1.1 g, 6.2 mmol) was dissolved in 100 mL of anhydrous tetrahydrofuran. To the resultant reaction solution hydrazine (0.19 mL, 6.2 mmol) and potassium carbonate (2.6 g, 18 mmol) were added and the reaction mixture was stirred for 3 days. The potassium carbonate was removed by filtration and the filtrate was concentrated in vacuo. Crystallization of the residue from ethyl acetate :hexanes yielded 414 mg (39percent) of the title compound.IH NMR: (OMSO-d6, 400 MHz) delta 8.80 (s, IH), 6.49 (brs, IH), 4.50 (brs, 2H), 3.77 (s, 3H).
  • 20
  • [ 885068-00-8 ]
  • [ 1074-40-4 ]
  • [ 1098269-51-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; water; at 50.0℃; for 3.0h; Step 1: To an 1 -L reactor are added <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (50.1 g), K2CO3 (96.4 g,), Pd(OAc)2 (48 mg, 0.1 molpercent) and PPh3 (120 mg, 0.2 molpercent) in DME/water (100 mL/200 mL). The mixture is heated to 5O°C, while 3-(l-carboxy-l-methyl-ethyl)-phenyl boronic acid (51.6 g, 94wtpercent purity) in DME (50 mL)/water (100 mL) is added over 2 h via a metering pump. The reaction is held at 5O°C for an additional hour. The mixture is cooled to 25°C and toluene (250 mL) is added. The mixture is stirred for 15 min and the layers are separated. To the aqueous layer is added n-BuOAc (300 mL) and pH is adjusted to 7.2 with 4 M aqueous HCl (~ 190 mL). The aqueous layer is extracted with n-BuOAc (2 x 300 mL). The combined organic layers are treated with TMT (3.2 g) and charcoal (6.4 g) at 7O°C for 3 h. The mixture is allowed to cool to 25°C and filtered through celite. The filtrate is extracted twice with an aqueous K2CO3 solution (31.8 g OfK2CO3 in 320 mL of water). The combined aqueous layers are used directly in the next step.
  • 21
  • [ 1074-40-4 ]
  • 2-(4-trifluoromethoxy-phenyl)-ethylamine hydrochloride [ No CAS ]
  • [ 885066-11-5 ]
YieldReaction ConditionsOperation in experiment
97% With sodium hydrogencarbonate; In ethanol; at 90.0℃; for 17.0h; E. (6-Chloro-2-methoxy-pyrimidin-4-yl)-r2-(4-trifluoromethoxy-phenyl)-ethyl1-amineA suspension of 2-(4-trifluoromethoxy-phenyl)-ethylamine hydrochloride (24.50 g, 101.39 mmol), <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (18.15 g, 101.39 mmol) and sodium hydrogen carbonate (21.29 g, 253.47 mmol) in 300 mL of ethyl alcohol was refluxed at 90°C for 17 hours. After cooling to room temperature, the reaction was diluted with 450 mL of water and stirring continued for 1.5 hours. The formed precipitate was filtered and air dried to give title compound (34.25 g, 97percent). LC/MS: Rt = 3.37 minutes, MS m/z = 348.
97% With sodium hydrogencarbonate; In ethanol; at 90.0℃; for 17.0h; Step 2 (6-Chloro-2-methoxy-pyrimidin-4-yl)-r2-(4-trifluoromethoxy-phenyl)-ethyl1-amine (5). A suspension of 2-(4-trifluoromethoxy-phenyl)-ethylamine hydrochloride (3) (24.50 g, 101.39 mmol), <strong>[1074-40-4]4,6-dichloro-2-methoxy-pyrimidine</strong> (4) (18.15 g, 101.39 mmol) and sodium hydrogen carbonate (21.29 g, 253.47 mmol) in 300 mL of ethyl alcohol was refluxed at 90°C for 17 hours. After cooling to room temperature, the reaction was diluted with 450 mL of water and stirring continued for 1.5 hours. The formed precipitate was filtered and air dried to give title compound (5) (34.25 g, 97percent). LC/MS: Rt = 3.37 minutes, MS m/z = 348.
  • 22
  • [ 886547-94-0 ]
  • [ 1074-40-4 ]
  • [ 1365534-19-5 ]
  • 23
  • [ 67-56-1 ]
  • [ 4489-34-3 ]
  • [ 1074-40-4 ]
  • 24
  • [ 1074-40-4 ]
  • [ 1365534-20-8 ]
  • 25
  • [ 1074-40-4 ]
  • [ 1231748-80-3 ]
  • 26
  • [ 1074-40-4 ]
  • [ 1231748-82-5 ]
  • 27
  • [ 1231749-32-8 ]
  • [ 1074-40-4 ]
  • [ 1231749-92-0 ]
YieldReaction ConditionsOperation in experiment
42% With potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃; for 2.0h; Step 3: 6-(6-chloro-2-methoxypyrimidin-4-yloxy)-4-methylbenzo[d]oxazol-2(3H)-one; 0.19 g (1.01 mmol) <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong>, 0.18 g (1.04 mmol) 6-hydroxy-4-methyl-3H-benzoxazol-2-one and 0.15 g (1.09 mmol) potassium carbonate in 1.5 mL DMF were stirred for 2 h at RT. Then water was added and the precipitate formed was suction filtered, washed and dried.Yield: 145 mg (42percent of theory)ESI-MS: m/z=308/310 (Cl) (M+H)+ Rt(HPLC): 1.41 min (method B)
  • 28
  • [ 67-56-1 ]
  • [ 3764-01-0 ]
  • [ 43212-41-5 ]
  • [ 1074-40-4 ]
  • 29
  • [ 1074-40-4 ]
  • 3-(6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-2-methoxypyrimidin-4-yl)propanoic acid [ No CAS ]
  • 30
  • [ 292638-85-8 ]
  • [ 1074-40-4 ]
  • methyl 3-(6-chloro-2-methoxypyrimidin-4-yl)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
330 mg With tris-(dibenzylideneacetone)dipalladium(0); tetrabutyl-ammonium chloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 90.0℃; for 15.0h; A) methyl 3-(6-chloro-2-methoxypyrimidin-4-yl)acrylate To a solution of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (780 mg) in DMF (10 mL) were added methyl acrylate (760 mg), tris(dibenzylideneacetone)dipalladium (200 mg), N-ethyldiisopropylamine (1.14 g) and tetrabutylammonium chloride (61 mg), and the mixture was stirred at 90°C for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (330 mg) as a white solid. MS (ESI+): [M+H]+229.0
  • 31
  • [ 1074-40-4 ]
  • 3-(6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-2-methoxypyrimidin-4-yl)acrylic acid [ No CAS ]
  • 32
  • [ 110-91-8 ]
  • [ 1074-40-4 ]
  • 4-(6-chloro-2-methoxypyrimidin-4-yl)morpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With sodium hydrogencarbonate; In ethanol; for 3.0h;Reflux; A mixture of <strong>[1074-40-4]4,6-dichloro-2-methoxypyrimidine</strong> (700 mg, 3.91 mmol), morpholine (340 mg, 3.91 mmol) and NaHCO3 (822 mg, 9.78 mmol) in ethanol (20 mL) was refluxed for 3 hrs.Then the reaction was cooled to ii and diluted with 20 mL of water. The mixture was stirred for 30 mm and filtered. The solid was collected and washed with water and ether. The title compound (660 mg, yield 73percent) was obtained after dried under vacuum as a white solid.1H NMR (300 MHz, CDCI3): O 6.18 (s, 1H), 3.93 (s, 3H), 3.77-3.74 (m, 4H), 3.63-3.61 (m, 4H).
  • 33
  • [ 1074-40-4 ]
  • 4-(6-(6-(3,3-difluoro-1-(oxetan-3-yl)piperidin-4-yl)-5-methyl-1H-indazol-1-yl)-2-methoxypyrimidin-4-yl)morpholine [ No CAS ]
  • 34
  • [ 1074-40-4 ]
  • 4-(6-(6-(3,3-difluoro-1-(oxetan-3-yl)piperidin-4-yl)-5-methyl-1H-indazol-1-yl)-2-methoxypyrimidin-4-yl)morpholine [ No CAS ]
  • 35
  • [ 1074-40-4 ]
  • (cis)-1-(6-(6-(3-fluoro-1-methylpiperidin-4-yl)-5-methyl-1H-indazol-1-yl)-2-methoxypyrimidin-4-yl)azetidin-3-ol [ No CAS ]
 

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Technical Information

Categories

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[ 1074-40-4 ]

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