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[ CAS No. 22536-61-4 ] {[proInfo.proName]}

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Chemical Structure| 22536-61-4
Chemical Structure| 22536-61-4
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Product Details of [ 22536-61-4 ]

CAS No. :22536-61-4 MDL No. :MFCD09260903
Formula : C5H5ClN2 Boiling Point : -
Linear Structure Formula :- InChI Key :APRMCBSTMFKLEI-UHFFFAOYSA-N
M.W : 128.56 Pubchem ID :581719
Synonyms :

Calculated chemistry of [ 22536-61-4 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.2
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 32.01
TPSA : 25.78 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.0 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.72
Log Po/w (XLOGP3) : 1.53
Log Po/w (WLOGP) : 1.44
Log Po/w (MLOGP) : 0.54
Log Po/w (SILICOS-IT) : 2.04
Consensus Log Po/w : 1.45

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.16
Solubility : 0.898 mg/ml ; 0.00698 mol/l
Class : Soluble
Log S (Ali) : -1.68
Solubility : 2.68 mg/ml ; 0.0209 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.62
Solubility : 0.311 mg/ml ; 0.00242 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.36

Safety of [ 22536-61-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 22536-61-4 ]

* 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.

  • Upstream synthesis route of [ 22536-61-4 ]
  • Downstream synthetic route of [ 22536-61-4 ]

[ 22536-61-4 ] Synthesis Path-Upstream   1~11

  • 1
  • [ 1780-36-5 ]
  • [ 2036-41-1 ]
  • [ 22536-61-4 ]
Reference: [1] Chemische Berichte, 1905, vol. 38, p. 3397
  • 2
  • [ 22536-61-4 ]
  • [ 50840-23-8 ]
YieldReaction ConditionsOperation in experiment
92% With ammonia In ethanol; water at 200℃; for 4 h; Sealed tube Step 1 : To a solution of compound 184 (10.0 g, 77.79 mmol) in IMS (100 ml.) was added aqueous ammonia (35percent, 100 ml). The reaction mixture was transferred to a sealed bomb and heated at 200 °C for 4 h. The reaction mixture was allowed to cool to room temperature and was concentrated to remove most of the solvent and water (25 ml.) added. The solid obtained was filtered and dried under vacuum to give the desired compound 185 as off-white solid (7.85 g, 92percent yield).1H NMR (400 MHz, DMSO-d6) δ 8.06 (s, 2H), 6.30 (s, 2H), 2.03 (s, 3H). LCMS m/z 1 10 [M+H]+.
Reference: [1] Patent: WO2013/132376, 2013, A1, . Location in patent: Page/Page column 205
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 11, p. 4720 - 4744
[3] Chemische Berichte, 1905, vol. 38, p. 3397
[4] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 5, p. 1261 - 1266
  • 3
  • [ 22536-61-4 ]
  • [ 7664-41-7 ]
  • [ 50840-23-8 ]
Reference: [1] Chemische Berichte, 1905, vol. 38, p. 3397
  • 4
  • [ 1780-31-0 ]
  • [ 22536-61-4 ]
YieldReaction ConditionsOperation in experiment
78% With zinc In water for 3 h; Reflux Step 1 : A suspension of compound 242 (50.0 g, 307 mmol) and freshly activated (acid washed) Zn (59.8 g, 920 mmol) in water (500 mL) was heated at reflux for 3 hours. TLC showed consumption of SM. The reaction mixture was cooled to room temperature, filtered through a pad of celite, and rinsed with CH2CI2 (500 mL). The phases of the filtrate were separated and the organic phase was washed with brine (300 mL), dried over MgS04, filtered and concentrated under vacuum carefully to give compound 243 as a beige powder (30.6 g, 78percent yield, 95percent purity by 1 H NMR).1 H NMR (400 MHz, DMSO-d6) δ 8.63 (d, J = 0.9 Hz, 2H), 2.27 (t, J = 0.8 Hz, 3H).
77% With ammonium hydroxide; zinc In water; benzene for 18 h; Reflux Step 1.
Preparation of 2-chloro-5-methylpyrimidine
To a stirred solution of 2,4-dichloro-5-methylpyrimidine (4.00 g, 24.5 mmol) in a mixture of benzene (16.0 mL) and H2O (40.0 mL) was added zinc powder (4.81 g, 73.6 mmol) and ammonia water (8.80 mL, 24.5 mmol) at room temperature.
After heating at reflux for 18 hours, the reaction mixture was cooled and filtered through a pad of Celite and the reaction mixture was extracted with Et2O, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo.
The residue was purified by column chromatography on SiO2 (Hexanes:EtOAc=1:1) to give the desired product (2.44 g, 77percent) as a yellow oil. 1H-NMR (400 MHz, CDCl3) δ 2.33 (3H, s), 8.47 (2H, s).
75% Reflux A mixture of 2,4-dichloro-5-methylpyrimidine (50 g, 0.31 mol), water (500 mL) and zinc dust (50 g, 0.94 mol) was heated at reflux overnight.
The reaction mixture was filtered and the filtrate was extracted with dichloromethane (3*500 mL).
The organic layer was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo.
The residue was recrystallized from petroleum ether to afford compound C60 as a white solid. Yield: 27.9 g, 0.22 mol, 75percent. LCMS m/z 129.3 (M+1).
1H NMR (400 MHz, CDCl3) δ 2.25 (s, 3H), 8.40 (5, 2H).
69%
Stage #1: With acetic acid; zinc In tetrahydrofuran for 3.66667 h;
Stage #2: With sodium hydroxide; water In dichloromethane; ethyl acetate
EXAMPLE 84[4-(6-Bromobenzo[b]thiophen-2-yl)-5-methylpyrimidin-2-yl]-[3-(4-methylpiperazin-1-yl)-propyl]-amine tri-hydrochloride(A). Preparation of 2-chloro-5-methylpyrimidine; Into a 3-necked, 500 mL round bottomed flask is added 2,4-dichloro-5-methylpyrimidine (25.0 g, 153 mmol), THF (125 mL) and zinc powder (30.1 g, 460 mmol). The mixture is heated to reflux and acetic acid (HOAc) (9.21 g, 153 mmol) in THF (20 mL) is dropwise added over 1 hour. After 1.5 hours at reflux, additional HOAc (3.93 g, 65.5 mmol) in THF (12.5 mL) is added over 10 minutes, and the mixture is refluxed for an additional 1 hour. The mixture is filtered over celite, rinsed with THF (150 mL) and the organic layers are concentrated under reduced pressure. The crude mixture is partitioned in EtOAc/dichloromethane/1 N NaOH and filtered. The organic layer is concentrated under reduced pressure to yield a peach colored solid. The crude material is subjected to chromatography on silica (in hexane) to provide the title compound as a white solid (13.5 g, 69percent yield).

Reference: [1] Patent: WO2013/132376, 2013, A1, . Location in patent: Page/Page column 224
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 11, p. 4720 - 4744
[3] Patent: US2012/53180, 2012, A1, . Location in patent: Page/Page column 8
[4] Patent: US2010/190771, 2010, A1, . Location in patent: Page/Page column 33
[5] Patent: US2008/306082, 2008, A1, . Location in patent: Page/Page column 26-27
[6] Patent: WO2004/22553, 2004, A1, . Location in patent: Page/Page column 34
[7] Patent: WO2008/85316, 2008, A1, . Location in patent: Page/Page column 97
[8] Patent: US2005/234046, 2005, A1, . Location in patent: Page/Page column 63
  • 5
  • [ 41398-85-0 ]
  • [ 22536-61-4 ]
YieldReaction ConditionsOperation in experiment
2.8 g at 90℃; A solution of Example 52B (8.8g, 79.9mmol) in phosphorus oxychloride (50mL) was stirred overnight at 90°C.The reaction solution was poured into ice water, and sodium bicarbonate solution was added, the aqueous layer wasextracted with dichloromethane. The organic layer was concentrated to give the title compound (2.8g). 1H NMR (400MHz, DMSO-d6) ppm 2.27 (s, 3 H) 8.64 (s, 2 H).
Reference: [1] Patent: EP3333157, 2018, A1, . Location in patent: Paragraph 0312; 0313
  • 6
  • [ 75-24-1 ]
  • [ 32779-36-5 ]
  • [ 22536-61-4 ]
Reference: [1] Acta Chemica Scandinavica, 1997, vol. 51, # 3, p. 302 - 306
  • 7
  • [ 1780-36-5 ]
  • [ 2036-41-1 ]
  • [ 22536-61-4 ]
Reference: [1] Chemische Berichte, 1905, vol. 38, p. 3397
  • 8
  • [ 22536-61-4 ]
  • [ 99420-75-4 ]
Reference: [1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1993, vol. 29, # 4, p. 427 - 431[2] Khimiya Geterotsiklicheskikh Soedinenii, 1993, # 4, p. 503 - 508
  • 9
  • [ 22536-61-4 ]
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 76196-80-0 ]
YieldReaction ConditionsOperation in experiment
350 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In N,N-dimethyl-formamide at 120℃; for 16 h; To a solution of 2-chloro-5-methyl-pyrimidine (500.00 mg, 3.89 mmol, 1.00 eq) in MeOH (10.00 mL) and DMF (2.00mL) was added triethylamine (1.18 g, 11.67 mmol, 1.62 mL, 3.00 eq) and Pd(dppf)C12 (426.87 mg, 583.39 umol, 0.15 eq) under CO. The suspension was degassed and purged with CO several times. The mixture was stirred under CO (3 Mpa) at 120°C for 16 h. The reaction mixture was filtered and the filtrate was concentrated. The crude residue was purified by column chromatography (Petroleum ether : Ethyl acetate=20: l to 0: 1) to afford methyl 5-methylpyrimidine-2-carboxylate (350.00 mg). LCMS (M+H+) m/z: 153.
Reference: [1] Patent: WO2013/142269, 2013, A1, . Location in patent: Paragraph 0613; 0614; 0615
[2] Patent: WO2016/172496, 2016, A1, . Location in patent: Paragraph 00170-00171
  • 10
  • [ 22536-61-4 ]
  • [ 182924-36-3 ]
YieldReaction ConditionsOperation in experiment
38% With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 6 h; Reflux Synthesis Example 25
N-[1-((2-chloropyrimidin-5-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (Compound 243)
2-chloro-5-methylpyrimidine (1.04 g, 8.13 mmol) was dissolved in 30 mL of carbon tetrachloride, 1.73 g (9.75 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added, and the mixture was refluxed under heating for 6 hours.
Following reaction completion, the reaction mixture was returned to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography (hexane/ethyl acetate=3:1), affording 641 mg of 5-bromomethyl-2-chloropyridine (yield, 38percent).
1H-NMR (CDCl3, δ, ppm): 4.42 (2H, s), 8.66 (2H, s)
Reference: [1] Patent: US2013/150414, 2013, A1, . Location in patent: Paragraph 0437
  • 11
  • [ 22536-61-4 ]
  • [ 69034-12-4 ]
Reference: [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1984, vol. 38, # 6, p. 505 - 508
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