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[ CAS No. 22536-65-8 ] {[proInfo.proName]}

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Chemical Structure| 22536-65-8
Chemical Structure| 22536-65-8
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Product Details of [ 22536-65-8 ]

CAS No. :22536-65-8 MDL No. :MFCD08702770
Formula : C5H5ClN2O Boiling Point : -
Linear Structure Formula :- InChI Key :RSUBGBZOMBTDTI-UHFFFAOYSA-N
M.W : 144.56 Pubchem ID :589058
Synonyms :

Calculated chemistry of [ 22536-65-8 ]

Physicochemical Properties

Num. heavy atoms : 9
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 : 33.53
TPSA : 35.01 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.37 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.81
Log Po/w (XLOGP3) : 1.14
Log Po/w (WLOGP) : 1.14
Log Po/w (MLOGP) : -0.07
Log Po/w (SILICOS-IT) : 1.56
Consensus Log Po/w : 1.12

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.88
Solubility : 1.9 mg/ml ; 0.0131 mol/l
Class : Very soluble
Log S (Ali) : -1.47
Solubility : 4.91 mg/ml ; 0.0339 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.37
Solubility : 0.612 mg/ml ; 0.00424 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.85

Safety of [ 22536-65-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 22536-65-8 ]

* 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 [ 22536-65-8 ]
  • Downstream synthetic route of [ 22536-65-8 ]

[ 22536-65-8 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 22536-65-8 ]
  • [ 13418-77-4 ]
YieldReaction ConditionsOperation in experiment
55% With ammonia In water at 150℃; for 3 h; Irradiation A MW reaction vessel was charged with 2-chloro-5- methoxypyrimidine (0.817 g, 5.65 mmol) and 25percent NH3(aq). The vessel was capped and heated to 150 0C for 3h. The mixture was evaporated to dryness. The resulting material was dissolved in CH2Cl2MeOH (1 : 1) and adsorbed onto silica. Purification by flash CC (eluent: 50-100 percent EtOAc in heptane) gave the title compound as colorless crystals (386 mg, 55percent). 1H NMR (400 MHz, dmso-d6) δ 8.02 (s, IH), 6.06 (br s, IH), 3.71 (s, 3H).
45% at 100℃; for 18 h; Sealed tube A mixture of 2-chloro-5-methoxypyrimidine (7 g, 48.4 mmol) and ammonium hydroxide (113 mL, 2905 mmol) was heated at 100 °C in a sealed tube for 18 h. The mixture was cooled to rt and was concentrated. The residue was was purified on silica gel using 40-80 percent ethyl acetate in hexanes. The desired fractions were concentrated to give a pale yellow solid (2.75 g, 45 percent). 1H NMR (400 MHz, CDCl3) d ppm 8.02 (2 H, s), 4.80 (2 H, br. s.), 3.79 (3 H, s). LCMS (method B) tR, 0.81 min., MH+ = 293.3.
Reference: [1] Patent: WO2008/141239, 2008, A1, . Location in patent: Page/Page column 54
[2] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 5, p. 1261 - 1266
  • 2
  • [ 22536-65-8 ]
  • [ 4983-28-2 ]
YieldReaction ConditionsOperation in experiment
62%
Stage #1: With boron tribromide In dichloromethane at 20℃;
Stage #2: With sodium hydrogencarbonate In dichloromethane; water
2-Chloro-5-methoxypyrimidine (0.46 g, 3.18 mmol) in methylene chloride (10 mL) was treated with 1.0 N boron tribromide (16 mL, 16 mmol) at room temperature. The solution was stirred overnight. After this time the reaction was partitioned between saturated NaHCO3 and DCM. The aqueous layer was extraxted with additional DCM. The combined organic layers were dried (MgSO4), filtered, and concnetrated. The residue was purified by flash column chromatography on silica gel to give 0.26 g of compound 112A (62percent): 1H NMR (DMSO-D6): δ 10.03 (s, IH), 8.30 (s, 2H), ESI (-)/MS: 129 (M-H)-.
61% With boron tribromide In dichloromethane at 20℃; for 20 h; Intermediate 4: 2-Chloro-5-hydroxypyrimidineTo a solution of 2-chloro-5-methoxypyrimidine (lOg, 0.069mol) in dichloromethane (84mL) was added dropwise boron tribromide (104mL, 1M solution in dichloromethane) at -78°C. The mixture was stirred at room temperature for 20h and then methanol (150mL) was added dropwise at -78°C. The reaction mixture was concentrated under reduced pressure and the pH adjusted to 5 with aq. sodium hydroxide solution. The mixture was extracted with ethyl acetate and washed with water and brine. The organic phase was dried (MgS04) and the solvent removed under reduced pressure to give 2-chloro-5-hydroxypyrimidine (5.7g, 61percent).Mass: (ES-) 129NMR: 5H (d6-DMSO) 8.27 (2H, s) and 10.85 (1H, br s).
55%
Stage #1: With boron tribromide In dichloromethane at -78 - 20℃; for 20 h;
Stage #2: With methanol In dichloromethane at -78℃;
Stage #3: With sodium hydroxide In methanol; water
Intermediate 4: 2-Chloro-5-hydroxypyrimidine To a solution of 2-chloro-5-methoxypyrimidine (lOg, 0.069mol) in dichloromethane (84mL) was added dropwise boron tribromide (104mL, 1M solution in dichloromethane) at -78°C. The mixture was stirred at room temperature for 20h and then methanol (150mL) was added dropwise at -78°C. The reaction mixture was concentrated under reduced pressure and the pH adjusted to 5 with aq. sodium hydroxide solution. The mixture was extracted with ethyl acetate and washed with water and brine. The organic phase was dried (MgS04) and the solvent removed under reduced pressure to give 2-chloro-5-hydroxypyrimidine (5.0g, 55percent).Mass: (ES-) 129NMR: 5H (d6-DMSO) 8.27 (2H, s) and 10.85 (1H, br s).
27% With boron tribromide In dichloromethane at 0 - 20℃; for 16 h; Boron tribromide (30mL) was slowly added to a solution of 2-chloro-5-methoxypyrimidine (2g, 13.83mmol) in DCM (lOmL) at 0 °C. Allowed the reaction mass to stir at room temperature for 16h. Then the reaction mixture was slowly quenched with ice cold water, warmed to room temperature and diluted with DCM (lOOmL). The aqueous layer was separated and extracted with DCM (3x25mL). The organic phase was washed with brine, dried over Na2S04, filtered and concentrated under vacuum. The residue was purified by silica gel column chromatography to afford desired title compound (0.5g, 27percent) as a solid. LCMS: m/z = 129.0 (M-H)+ (Negative mode).

Reference: [1] Patent: WO2010/80503, 2010, A1, . Location in patent: Page/Page column 225
[2] Patent: WO2011/144578, 2011, A1, . Location in patent: Page/Page column 27
[3] Patent: WO2011/144577, 2011, A1, . Location in patent: Page/Page column 24-25
[4] Patent: WO2016/164703, 2016, A1, . Location in patent: Page/Page column 50
[5] Patent: US5589478, 1996, A,
[6] Patent: US2011/82165, 2011, A1, . Location in patent: Page/Page column 61-62
  • 3
  • [ 19646-07-2 ]
  • [ 22536-65-8 ]
YieldReaction ConditionsOperation in experiment
58% With water; zinc In ethanol for 4 h; Reflux Intermediate 3: 2-Chloro-5-methoxypyrimidine2,4-Dichloro-5-methoxypyrimidine (43g, 0.24mol), zinc dust (86g, 1.32mol), ethanol (200 mL) and water (200 mL) were heated under reflux for 4h. The hot mixture was filtered and the ethanol was removed under reduced pressure. After cooling, the product was collected in ether. Recrystallisation from light petroleum (b.p.: 40-60°C) gave 2-chloro-5-methoxypyrimidine (20g, 58percent).
58% With zinc In ethanol; water for 4 h; Reflux Intermediate 3: -Chloro-5-methoxypyrimidine2,4-Dichloro-5-methoxypyrimidine (43g, 0.24mol), zinc dust (86g, 1.32mol), ethanol (200 mL) and water (200 mL) were heated under reflux for 4h. The hot mixture was filtered and the ethanol was removed under reduced pressure. After cooling, the product was extracted into diethyl ether. Recrystallisation from light petroleum (b.p.: 40-60°C) gave 2-chloro-5-methoxypyrimidine (20g, 58percent).Mass: (ES+) 145 (M+H)+ NMR: 5H ( 6-DMSO) 3.92 (3H, s) and 8.55 (2H, s).
Reference: [1] Patent: WO2011/144577, 2011, A1, . Location in patent: Page/Page column 24
[2] Patent: WO2011/144578, 2011, A1, . Location in patent: Page/Page column 27
  • 4
  • [ 6623-81-0 ]
  • [ 22536-65-8 ]
Reference: [1] Patent: WO2011/144577, 2011, A1,
[2] Patent: WO2011/144578, 2011, A1,
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