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[ CAS No. 145783-15-9 ] {[proInfo.proName]}

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Chemical Structure| 145783-15-9
Chemical Structure| 145783-15-9
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Product Details of [ 145783-15-9 ]

CAS No. :145783-15-9 MDL No. :MFCD16875503
Formula : C7H9Cl2N3S Boiling Point : -
Linear Structure Formula :- InChI Key :CJJLJBFJNXMANZ-UHFFFAOYSA-N
M.W :238.14 Pubchem ID :11436336
Synonyms :

Calculated chemistry of [ 145783-15-9 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.43
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 57.79
TPSA : 77.1 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.49 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.32
Log Po/w (XLOGP3) : 3.18
Log Po/w (WLOGP) : 2.88
Log Po/w (MLOGP) : 1.47
Log Po/w (SILICOS-IT) : 2.65
Consensus Log Po/w : 2.5

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.46
Solubility : 0.0819 mg/ml ; 0.000344 mol/l
Class : Soluble
Log S (Ali) : -4.47
Solubility : 0.00807 mg/ml ; 0.0000339 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.84
Solubility : 0.0344 mg/ml ; 0.000145 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.33

Safety of [ 145783-15-9 ]

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

Application In Synthesis of [ 145783-15-9 ]

* 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.

  • Upstream synthesis route of [ 145783-15-9 ]
  • Downstream synthetic route of [ 145783-15-9 ]

[ 145783-15-9 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 145783-14-8 ]
  • [ 145783-15-9 ]
YieldReaction ConditionsOperation in experiment
100% With ammonium molibdate; hydrogen; hypophosphorous acid In tert-butyl methyl ether at 20 - 65℃; for 7 h; Inert atmosphere tert-Butyl methyl ether (370 g) was placed under nitrogen in a 1 L stainless steel autoclave equipped with a temperature-controlled jacket, an Ekato InterMIG.(R). stirrer, an internal temperature sensor and a dip pipe, and 4,6-dichloro-5-nitro-2-propylsulfanyl-pyrimidine (94.5 g, 0.35 mol) was added and dissolved at a stirring rate of 200 min-1.
The catalyst suspension was prepared and transferred into the autoclave as described in the preceding example.
The autoclave was sealed and the stirring rate was increased to 600 min-1 while the autoclave was purged four times with nitrogen.
Subsequently, hydrogen gas feed via the dip pipe at a constant flow rate (pmax=10 bar) as well as a heating-up ramp (45 K/h) from 20° C. to 65° C. were started in parallel, while stirring at 600 min-1.
The progress of the exothermic reaction was followed by recording the hydrogen uptake as well as the internal and jacket temperature curve.
Upon completion of the hydrogen uptake (ca. 1.1 mol or 3 molar equivalents) after about 4 h, stirring of the reaction mixture was continued for an additional 3 hours at 65° C.
After unloading the autoclave (the reactor was cooled down to 20° C., the hydrogen pressure was released and the reactor purged four times with nitrogen), the catalyst was filtered off.
The autoclave as well as the filter cake (catalyst) were washed with tent-butyl methyl ether (185 g).
The organic phases were combined and the water layer separated.
An IPC-sample was taken to analyze the product mixture.
The conversion was found to be quantitative with no nitroso or hydroxylamine intermediate being detectable.
1H NMR (CDCl3, 400 MHz): δ 4.24 (br. s, 2H), 3.08 (t, J=7.2 Hz, 2H), 1.74 (sext., J=7.2 Hz, 2H), 1.02 (t, J=7.2 Hz, 3H).
95%
Stage #1: With iron; acetic acid In methanol at 50℃;
Stage #2: With sodium hydrogencarbonate In water; ethyl acetate
Iron powder (15.62 g) was added to a solution of compound(16) in methanol (10 vol) and acetic acid (5.0 vol) at RT. The resulting reaction mixture was stirred for 3-5 hrs at 50°C. The reaction was monitored by TLC. The product was extracted by adding water (5.0vol). The resulting mixture was filtered and the filtrate was distilled off under reduced pressure at 40-50°C to form a residue. The obtained residue was extracted with ethyl acetate (500-600ml). The ethyl acetate extract was washed with aqueous sodium bicarbonate and then concentrated under reduced pressure. The thus obtained residue was crystallized. Isolated yield 90-95percent. NMR (400 MHz, CDC13): δ 4.22 (brs, 2H), 3.07 (t, J = 8Hz, 2H), 1.77-1.68 (m, 2H), 1.03 (t, J = 8Hz, 3H). "C NMR (100 MHz, CDC13) δ 158.60, 145.27, 131.48, 33.38, 22.42, 13.45.
73% for 4 h; To a mixture of Fe (167 g, 3 mol) in AcOH (1 L) 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (CLIN, 100 g, 0.37 mol) was slowly added over 2 h, and reaction mixture was then stirred at room temperature for additional 2 h.
Salts were then filtered off and the filtrate concentrated. EtOAc was added (400 mL), organic layer was washed with water (3 x 200 mL), dried over MgSO4, and concentrated to afford oily product (65.2 g, 73percent yield).
1H NMR (CDCl3, 500 MHz) δ 1.03 (t, J = 7.4 Hz, 3H), 1.73 (m, 2H), 3.07 (m, 2H), 4.23 (br s, 2H); MS (ESI) m/z: 238 [MH]+.
73% at 20℃; for 4 h; To a mixture of Fe (167 g, 3 mol) in AcOH (1 L) 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (CLIN, 100 g, 0.37 mol) was slowly added over 2 h, and reaction mixture was then stirred at room temperature for additional 2 h. Salts were then filtered off and the filtrate concentrated. EtOAc was added (400 mL), organic layer was washed with water (3 x 200 mL), dried over MgS04, and concentrated to afford oily product (65.2 g, 73percent yield). 1H N R (CDCI3. 500 MHz) δ 1.03 (t, J = 7.4 Hz, 3H), 1.73 (m, 2H), 3.07 (m, 2H), 4.23 (br s, 2H); MS (ESI) mlz: 238 [MHf .

Reference: [1] Patent: US2011/71290, 2011, A1, . Location in patent: Page/Page column 3
[2] Patent: WO2012/138981, 2012, A2, . Location in patent: Page/Page column 49
[3] Patent: EP2586773, 2013, A1, . Location in patent: Paragraph 0059-0060
[4] Patent: WO2013/60837, 2013, A1, . Location in patent: Page/Page column 26
[5] Patent: WO2005/95358, 2005, A2, . Location in patent: Page/Page column 5
[6] Patent: WO2010/30224, 2010, A1, . Location in patent: Page/Page column 7
[7] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 1, p. 436 - 449
[8] Patent: CN106432248, 2017, A, . Location in patent: Paragraph 0086; 0087
[9] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 1034 - 1041
[10] MedChemComm, 2017, vol. 8, # 8, p. 1655 - 1658
[11] Patent: CN106928235, 2017, A, . Location in patent: Paragraph 0058; 0059
[12] Patent: CN107033148, 2017, A, . Location in patent: Paragraph 0060; 0061
[13] European Journal of Medicinal Chemistry, 2018, vol. 146, p. 147 - 156
  • 2
  • [ 376608-73-0 ]
  • [ 145783-15-9 ]
Reference: [1] Patent: WO2005/95358, 2005, A2, . Location in patent: Page/Page column 5-6
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 11, p. 3598 - 3602
  • 3
  • [ 1549834-66-3 ]
  • [ 145783-15-9 ]
YieldReaction ConditionsOperation in experiment
96% for 22.5 h; Reflux; Sealed tube In a sealed tube, 5-amino-2-(propylthio)pyrimidine-4,6-diol (IIIA-HCI) of Example 3 (200 mg, 0.84 mmol) and POCI3 (2.5 mL) were mixed and the mixture was heated at reflux temperature for 22.5 h. Excess of POCI3 was evaporated at reduced pressure. Water (5 mL) and EtOAc (5 mL) were added, and the layers were separated. The aqueous layer was extracted with EtOAc (5 mL), and the combined organic layers were dried over MgSO4, were filtered and were evaporated providing 4,6-dichloro-2-(propylthio)pyrimidine-5-amine (192 mg, 96percent yield, 100percent HPLC-MS) as a brown oil.
96% for 22.5 h; Sealed tube; Reflux Example 4
Preparation of 4,6-dichloro-2-(propylthio)pyrimidine-5-amine (Compound of Formula IIA Wherein X is a Chlorine)
Procedure A:
In a sealed tube, 5-amino-2-(propylthio)pyrimidine-4,6-diol (IIIA-HCl) of Example 3 (200 mg, 0.84 mmol) and POCl3 (2.5 mL) were mixed and the mixture was heated at reflux temperature for 22.5 h.
Excess of POCl3 was evaporated at reduced pressure.
Water (5 mL) and EtOAc (5 mL) were added, and the layers were separated.
The aqueous layer was extracted with EtOAc (5 mL), and the combined organic layers were dried over MgSO4, were filtered and were evaporated providing 4,6-dichloro-2-(propylthio)pyrimidine-5-amine (192 mg, 96percent yield, 100percent HPLC-MS) as a brown oil.
Reference: [1] Patent: WO2014/23681, 2014, A1, . Location in patent: Page/Page column 30; 31
[2] Patent: US2015/152114, 2015, A1, . Location in patent: Paragraph 0143 - 0148; 0152 - 0153
  • 4
  • [ 145783-12-6 ]
  • [ 145783-15-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 11, p. 3598 - 3602
[2] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 1, p. 436 - 449
[3] Patent: CN106432248, 2017, A,
[4] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 1034 - 1041
[5] MedChemComm, 2017, vol. 8, # 8, p. 1655 - 1658
[6] Patent: CN106928235, 2017, A,
[7] Patent: CN107033148, 2017, A,
[8] European Journal of Medicinal Chemistry, 2018, vol. 146, p. 147 - 156
  • 5
  • [ 376608-72-9 ]
  • [ 145783-15-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 11, p. 3598 - 3602
  • 6
  • [ 1549834-56-1 ]
  • [ 145783-15-9 ]
Reference: [1] Patent: US2015/152114, 2015, A1,
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