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[ CAS No. 1260907-17-2 ] {[proInfo.proName]}

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Chemical Structure| 1260907-17-2
Chemical Structure| 1260907-17-2
Structure of 1260907-17-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1260907-17-2 ]

CAS No. :1260907-17-2 MDL No. :MFCD22417091
Formula : C22H22ClN5O2 Boiling Point : -
Linear Structure Formula :- InChI Key :AAAQFGUYHFJNHI-SFHVURJKSA-N
M.W : 423.90 Pubchem ID :46943432
Synonyms :
I-BET-762;GSK525762;GSK525762A

Calculated chemistry of [ 1260907-17-2 ]

Physicochemical Properties

Num. heavy atoms : 30
Num. arom. heavy atoms : 17
Fraction Csp3 : 0.27
Num. rotatable bonds : 6
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 119.37
TPSA : 81.4 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.86 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.18
Log Po/w (XLOGP3) : 2.85
Log Po/w (WLOGP) : 2.95
Log Po/w (MLOGP) : 2.44
Log Po/w (SILICOS-IT) : 4.2
Consensus Log Po/w : 3.12

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.29
Solubility : 0.0219 mg/ml ; 0.0000516 mol/l
Class : Moderately soluble
Log S (Ali) : -4.22
Solubility : 0.0257 mg/ml ; 0.0000605 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -7.65
Solubility : 0.0000094 mg/ml ; 0.0000000222 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 4.29

Safety of [ 1260907-17-2 ]

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 [ 1260907-17-2 ]

* 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 [ 1260907-17-2 ]
  • Downstream synthetic route of [ 1260907-17-2 ]

[ 1260907-17-2 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 1300019-38-8 ]
  • [ 75-04-7 ]
  • [ 1260907-17-2 ]
YieldReaction ConditionsOperation in experiment
47%
Stage #1: With N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran at 20℃; for 3 h;
Stage #2: for 48 h;
Example 1 : 2-[(4S)-6-(4-Chlorophenyl)-1 -methyl-8-(methyloxy)-4H-[1 ,2,4]triazolo[4,3- To a solution of [(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1 .2.4]triazolo[4,3- a][1 ,4]benzodiazepin-4-yl]acetic acid (for a preparation see Intermediate 1 )(16.0 g, 40 mmol) in THF at RT was added DIEA (14 mL, 80 mmol) followed by HATU (30.4 g, 80 mmol). The reaction mixture was stirred for 3h at this temperature and ethylamine (40 mL, 2M in THF, 80 mmol) was added. The mixture was stirred for 48h before being concentrated under reduced pressure. The crude material was suspended in water and extracted with DCM. The organic layer was dried over Na2S04, filtered and concentrated in vacuo. The crude solid was purified by chromatography on Si02 (DCM/MeOH 95/5) and the resulting solid recrystallised in MeCN. The solid was then dissolved in DCM and precipited with /'-Pr20 to give the title compound (8 g, 47percent yield) as a white solid. Rf = 0.48 (DCM/MeOH : 90/10). Mp >140 °C (becomes gummy). 1H NMR (300 MHz, CDCI3) 7.53-7.47 (m, 2H), 7.39 (d, J = 8.9 Hz, 1 H), 7.37-7.31 (m, 2H), 7.20 (dd, J = 2.9 and 8.9 Hz, 1 H), 6.86 (d, J = 2.9 Hz, 1 H), 6.40 (m, 1 H), 4.62 (m, 1 H), 3.80 (s, 3H), 3.51 (dd, J = 7.3 and 14.1 Hz, 1 H), 3.46-3.21 (m, 3H), 2.62 (s, 3H), 1.19 (t, J = 7.3 Hz, 3H). LC/MS : m/z 424 [M(35CI)+H]+, Rt 2.33 min.
47%
Stage #1: With N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran at 20℃; for 3 h;
Stage #2: for 48 h;
Example 1 : 2-r(4S)-6-(4-Chlorophenyl)-1 -methyl-8-(methyloxy)-4H-ri ,2,41triazolor4,3- alH ,41benzodiazepin-4-yll-/V-ethylacetamide To a solution of Intermediate 2 (16.0 g, 40 mmol) in THF at RT was added DIEA (14 mL, 80 mmol) followed by HATU (30.4 g, 80 mmol). The reaction mixture was stirred for 3h at this temperature and ethylamine (40 mL, 2M in THF, 80 mmol) was added. The mixture was stirred for 48h before being concentrated under reduced pressure. The crude material was suspended in water and extracted with DCM. The organic layer was dried over Na2S04, filtered and concentrated in vacuo. The crude solid was purified by chromatography on Si02 (DCM/MeOH 95/5) and the resulting solid recrystallised in MeCN. The solid was then dissolved in DCM and precipited with /'-Pr20 to give the title compound (8 g, 47percent yield) as a white solid. Rf = 0.48 (DCM/MeOH : 90/10). Mp >140 °C (becomes gummy). 1H RMN (300 MHz, CDCIs) 57.53-7.47 (m, 2H), 7.39 (d, J = 8.9 Hz, 1 H), 7.37-7.31 (m, 2H), 7.20 (dd, J = 2.9 and 8.9 Hz, 1 H), 6.86 (d, J = 2.9 Hz, 1 H), 6.40 (m, 1 H), 4.62 (m, 1 H), 3.80 (s, 3H), 3.51 (dd, J = 7.3 and 14.1 Hz, 1 H), 3.46-3.21 (m, 3H), 2.62 (s, 3H), 1 .19 (t, J = 7.3 Hz, 3H). LC/MS : m/z 424 [M(35CI)+H]+, Rt 2.33 min.
47%
Stage #1: With N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran at 20℃; for 3 h;
Stage #2: for 48 h;
EXAMPLE 1 2-[(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide To a solution of [(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid (for a preparation see Intermediate 1) (16.0 g, 40 mmol) in THF at RT was added DIEA (14 mL, 80 mmol) followed by HATU (30.4 g, 80 mmol). The reaction mixture was stirred for 3 h at this temperature and ethylamine (40 mL, 2M in THF, 80 mmol) was added. The mixture was stirred for 48 h before being concentrated under reduced pressure. The crude material was suspended in water and extracted with DCM. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude solid was purified by chromatography on SiO2 (DCM/MeOH 95/5) and the resulting solid recrystallised in MeCN. The solid was then dissolved in DCM and precipited with i-Pr2O to give the title compound (8 g, 47percent yield) as a white solid.Rf=0.48 (DCM/MeOH:90/10). Mp>140° C. (becomes gummy). 1H NMR (300 MHz, CDCl3) δ7.53-7.47 (m, 2H), 7.39 (d, J=8.9 Hz, 1H), 7.37-7.31 (m, 2H), 7.20 (dd, J=2.9 and 8.9 Hz, 1H), 6.86 (d, J=2.9 Hz, 1H), 6.40 (m, 1H), 4.62 (m, 1H), 3.80 (s, 3H), 3.51 (dd, J=7.3 and 14.1 Hz, 1H), 3.46-3.21 (m, 3H), 2.62 (s, 3H), 1.19 (t, J=7.3 Hz, 3H). LC/MS: m/z 424 [M(35Cl)+H]+, Rt 2.33 min.
Reference: [1] Patent: WO2011/54553, 2011, A1, . Location in patent: Page/Page column 26
[2] Patent: WO2011/54845, 2011, A1, . Location in patent: Page/Page column 55-56
[3] Patent: US2012/220573, 2012, A1, . Location in patent: Page/Page column 11-12
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 19, p. 7501 - 7515
  • 2
  • [ 67-56-1 ]
  • [ 75-04-7 ]
  • [ 1260907-17-2 ]
YieldReaction ConditionsOperation in experiment
85% With DIEA; HBTU In tetrahydrofuran; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; acetonitrile Example 2
2-[(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide
To a solution of Intermediate 1 (4.5 g, 11.4 mmol) in THF at r.t. was added DIEA (4 mL, 22.7 mmol) followed by HBTU (8.6 g, 22.7 mmol).
The reaction mixture was stirred for 3 h at this temperature and ethylamine (11.3 mL, 2M in THF, 22.7 mmol) was added dropwise.
The mixture was stirred overnight before being concentrated under reduced pressure.
The crude material was dissolved in DCM and washed successively with water, 1N NaOH and 1N HCl.
The organic layer was dried over Na2SO4, filtered and concentrated in vacuo.
The crude solid was recrystallised in MeCN to give the title compound (4.1 g, 85percent yield) as a white solid.
Rf=0.48 (DCM/MeOH:90/10).
Mp 140-145° C. (becomes gummy).
HRMS (M+H)+ calculated for C22H23ClN5O2 424.1540. found 424.1525.
Chiral HPLC: column: chiralpak AD 250*4.6 mm 10 μm; mobile phase: 60/40, EtOH/Hexane; Flow rate: 1.0 mL/min; UV wavelength: 210 and 254 nm.
Reference: [1] Patent: US2012/208800, 2012, A1,
  • 3
  • [ 1300019-48-0 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 19, p. 7501 - 7515
  • 4
  • [ 1300019-46-8 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 19, p. 7501 - 7515
  • 5
  • [ 1300019-43-5 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 19, p. 7501 - 7515
  • 6
  • [ 873-77-8 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
  • 7
  • [ 6705-03-9 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
  • 8
  • [ 38527-50-3 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
  • 9
  • [ 91713-54-1 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
  • 10
  • [ 1300019-40-2 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
[3] Patent: US2012/220573, 2012, A1,
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 19, p. 7501 - 7515
  • 11
  • [ 1300019-41-3 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: US2012/220573, 2012, A1,
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 19, p. 7501 - 7515
  • 12
  • [ 1300019-41-3 ]
  • [ 1260907-17-2 ]
Reference: [1] Patent: WO2011/54553, 2011, A1,
[2] Patent: WO2011/54845, 2011, A1,
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