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[ CAS No. 603288-22-8 ] {[proInfo.proName]}

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Chemical Structure| 603288-22-8
Chemical Structure| 603288-22-8
Structure of 603288-22-8 * Storage: {[proInfo.prStorage]}
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Product Details of [ 603288-22-8 ]

CAS No. :603288-22-8 MDL No. :MFCD20526532
Formula : C28H25FN6O3 Boiling Point : -
Linear Structure Formula :- InChI Key :HRJWTAWVFDCTGO-UHFFFAOYSA-N
M.W : 512.53 Pubchem ID :10029385
Synonyms :

Calculated chemistry of [ 603288-22-8 ]

Physicochemical Properties

Num. heavy atoms : 38
Num. arom. heavy atoms : 18
Fraction Csp3 : 0.29
Num. rotatable bonds : 4
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 150.49
TPSA : 91.95 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 : No
Log Kp (skin permeation) : -7.67 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.05
Log Po/w (XLOGP3) : 2.48
Log Po/w (WLOGP) : 2.54
Log Po/w (MLOGP) : 2.56
Log Po/w (SILICOS-IT) : 2.32
Consensus Log Po/w : 2.59

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.67
Solubility : 0.011 mg/ml ; 0.0000215 mol/l
Class : Moderately soluble
Log S (Ali) : -4.06
Solubility : 0.0451 mg/ml ; 0.000088 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -6.5
Solubility : 0.000163 mg/ml ; 0.000000318 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 4.12

Safety of [ 603288-22-8 ]

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 [ 603288-22-8 ]

* 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.

  • Downstream synthetic route of [ 603288-22-8 ]

[ 603288-22-8 ] Synthesis Path-Downstream   1~20

  • 4
  • [ 395-81-3 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: 95 percent / TsOH / toluene / 3 h / Heating 2.1: tetrahydrofuran / 0.67 h / -40 °C 2.2: 55 percent / 0.5 N aq. HCl / tetrahydrofuran / 1 h / 0 °C 3.1: 93 percent / H2 / Pd/c / methanol / 3 h / 20 °C / 760 Torr 4.1: 86 percent / aq. K2CO3 / tetrahydrofuran / 4 h / 0 °C 5.1: 100 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 6.1: 76 percent / NaH / dimethylformamide / 1 h / 0 °C 7.1: CH2Cl2 / 1 h / 0 °C 7.2: 98 percent / methanol; CH2Cl2 / -78 - 20 °C 8.1: KOt-Bu / tetrahydrofuran / 2 h / 20 °C 9.1: 1.15 g / aq. HCl / CH2Cl2; dioxane / 1.5 h / 20 °C 10.1: 60 percent / Et3N / methanol / 3 h / 20 °C
  • 5
  • [ 320-98-9 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 12 steps 1.1: 100 percent / BH3*THF / 72 h / 20 °C 2.1: 69 percent / PDC; 4 Angstroem molecular sieves / CH2Cl2 / 6 h / 20 °C 3.1: 95 percent / TsOH / toluene / 3 h / Heating 4.1: tetrahydrofuran / 0.67 h / -40 °C 4.2: 55 percent / 0.5 N aq. HCl / tetrahydrofuran / 1 h / 0 °C 5.1: 93 percent / H2 / Pd/c / methanol / 3 h / 20 °C / 760 Torr 6.1: 86 percent / aq. K2CO3 / tetrahydrofuran / 4 h / 0 °C 7.1: 100 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 8.1: 76 percent / NaH / dimethylformamide / 1 h / 0 °C 9.1: CH2Cl2 / 1 h / 0 °C 9.2: 98 percent / methanol; CH2Cl2 / -78 - 20 °C 10.1: KOt-Bu / tetrahydrofuran / 2 h / 20 °C 11.1: 1.15 g / aq. HCl / CH2Cl2; dioxane / 1.5 h / 20 °C 12.1: 60 percent / Et3N / methanol / 3 h / 20 °C
  • 6
  • [ 287121-32-8 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 11 steps 1.1: 69 percent / PDC; 4 Angstroem molecular sieves / CH2Cl2 / 6 h / 20 °C 2.1: 95 percent / TsOH / toluene / 3 h / Heating 3.1: tetrahydrofuran / 0.67 h / -40 °C 3.2: 55 percent / 0.5 N aq. HCl / tetrahydrofuran / 1 h / 0 °C 4.1: 93 percent / H2 / Pd/c / methanol / 3 h / 20 °C / 760 Torr 5.1: 86 percent / aq. K2CO3 / tetrahydrofuran / 4 h / 0 °C 6.1: 100 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 7.1: 76 percent / NaH / dimethylformamide / 1 h / 0 °C 8.1: CH2Cl2 / 1 h / 0 °C 8.2: 98 percent / methanol; CH2Cl2 / -78 - 20 °C 9.1: KOt-Bu / tetrahydrofuran / 2 h / 20 °C 10.1: 1.15 g / aq. HCl / CH2Cl2; dioxane / 1.5 h / 20 °C 11.1: 60 percent / Et3N / methanol / 3 h / 20 °C
  • 7
  • [ 603306-52-1 ]
  • 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine [ No CAS ]
  • 8
  • [ 101820-69-3 ]
  • 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine [ No CAS ]
  • 9
  • [ 722539-10-8 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: 86 percent / aq. K2CO3 / tetrahydrofuran / 4 h / 0 °C 2.1: 100 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 3.1: 76 percent / NaH / dimethylformamide / 1 h / 0 °C 4.1: CH2Cl2 / 1 h / 0 °C 4.2: 98 percent / methanol; CH2Cl2 / -78 - 20 °C 5.1: KOt-Bu / tetrahydrofuran / 2 h / 20 °C 6.1: 1.15 g / aq. HCl / CH2Cl2; dioxane / 1.5 h / 20 °C 7.1: 60 percent / Et3N / methanol / 3 h / 20 °C
  • 10
  • [ 603306-58-7 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: tetrahydrofuran / 0.67 h / -40 °C 1.2: 55 percent / 0.5 N aq. HCl / tetrahydrofuran / 1 h / 0 °C 2.1: 93 percent / H2 / Pd/c / methanol / 3 h / 20 °C / 760 Torr 3.1: 86 percent / aq. K2CO3 / tetrahydrofuran / 4 h / 0 °C 4.1: 100 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 5.1: 76 percent / NaH / dimethylformamide / 1 h / 0 °C 6.1: CH2Cl2 / 1 h / 0 °C 6.2: 98 percent / methanol; CH2Cl2 / -78 - 20 °C 7.1: KOt-Bu / tetrahydrofuran / 2 h / 20 °C 8.1: 1.15 g / aq. HCl / CH2Cl2; dioxane / 1.5 h / 20 °C 9.1: 60 percent / Et3N / methanol / 3 h / 20 °C
  • 12
  • [ 722539-11-9 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: 100 percent / Et3N / tetrahydrofuran / 2 h / 0 °C 2.1: 76 percent / NaH / dimethylformamide / 1 h / 0 °C 3.1: CH2Cl2 / 1 h / 0 °C 3.2: 98 percent / methanol; CH2Cl2 / -78 - 20 °C 4.1: KOt-Bu / tetrahydrofuran / 2 h / 20 °C 5.1: 1.15 g / aq. HCl / CH2Cl2; dioxane / 1.5 h / 20 °C 6.1: 60 percent / Et3N / methanol / 3 h / 20 °C
  • 13
  • [ 722539-12-0 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: 76 percent / NaH / dimethylformamide / 1 h / 0 °C 2.1: CH2Cl2 / 1 h / 0 °C 2.2: 98 percent / methanol; CH2Cl2 / -78 - 20 °C 3.1: KOt-Bu / tetrahydrofuran / 2 h / 20 °C 4.1: 1.15 g / aq. HCl / CH2Cl2; dioxane / 1.5 h / 20 °C 5.1: 60 percent / Et3N / methanol / 3 h / 20 °C
  • 16
  • [ CAS Unavailable ]
  • [ 13939-69-0 ]
  • [ 771473-47-3 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
45% With triethylamine In methanol; ethyl acetate 1 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine EXAMPLE 1 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine Add piperidine-1-carbonyl chloride (0.5 mL, 4.0 mmol) to a solution of 3-(9-fluoro-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-4-imidazo[1,2-a]pyridin-3-yl-pyrrole-2,5-dione (1.42 g, 3.0 mmol) and triethylamine (2.09 mL, 15.0 mmol) in methanol (80 mL). Stir at room temperature over night. Add triethylamine (1.04 mL, 7.5 mmol) and piperidine-1-carbonyl chloride (0.5 mL, 4.0 mmol). Stir at room temperature for 5 hours. Add ethyl acetate (500 mL) and wash sequentially with saturated aqueous sodium bicarbonate (300 mL*3) and saturated aqueous sodium chloride (200 mL). Dry the organic phase over sodium sulfate and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluding with 0% to 3% methanol in ethyl acetate to provide the title compound as a red solid (700 mg, 45%). m.p.=188-190° C. MS (APCI): m/z=513 [C28H25FN6O3+H]+.
  • 17
  • [ 603288-22-8 ]
  • [ 1097945-22-6 ]
YieldReaction ConditionsOperation in experiment
88.5% With methanesulfonic acid In methanol; isopropyl alcohol 2 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine methanesulfonate EXAMPLE 2 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine methanesulfonate Heat a slurry of 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine (500 mg, 0.976 mmol) in methanol (2.5 mL) to 64° C. Add a solution of methanesulfonic acid (64 μL, 0.976 mmol) in methanol (1.0 mL) over 5 minutes. Stir the mixture at 64° C. for 15 minutes and then add isopropanol (5.0 mL) over 30 minutes. Allow the resulting slurry to cool to room temperature over 1 hour and then stir at room temperature for 4 hours. Filter the slurry, wash with isopropanol, and dry under reduced pressure at 42° C. to provide the title compound as an orange solid (478 mg, 88.5% (adjusted for 9.9% volatiles in starting material and 1.0% volatiles in product)). m.p.=282.3° C. (DSC)
  • 18
  • [ 21801-86-5 ]
  • [ 1239017-87-8 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
81% With potassium <i>tert</i>-butylate In tetrahydrofuran; N,N-dimethyl-formamide at 5 - 20℃; Inert atmosphere;
  • 19
  • [ 13939-69-0 ]
  • [ 771473-47-3 ]
  • [ 603288-22-8 ]
YieldReaction ConditionsOperation in experiment
45% With triethylamine In methanol at 20℃; 1 EXAMPLE 1 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine EXAMPLE 1 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine (0048) Add piperidine-1-carbonyl chloride (0.5 mL, 4.0 mmol) to a solution of 3-(9-fluoro-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-4-imidazo[1,2-a]pyridin-3-yl-pyrrole-2,5-dione (1.42 g, 3.0 mmol) and triethylamine (2.09 mL, 15.0 mmol) in methanol (80 mL). Stir at room temperature over night. Add triethylamine (1.04 mL, 7.5 mmol) and piperidine-1-carbonyl chloride (0.5 mL, 4.0 mmol). Stir at room temperature for 5 hours. Add ethyl acetate (500 mL) and wash sequentially with saturated aqueous sodium bicarbonate (300 mL×3) and saturated aqueous sodium chloride (200 mL). Dry the organic phase over sodium sulfate and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with 0% to 3% methanol in ethyl acetate to provide the title compound as a red solid (700 mg, 45%). m.p. = 188-190°C. MS(APCI): m/z = 513 [C28H25FN6O3 + H]+.
  • 20
  • [ 75-75-2 ]
  • [ 603288-22-8 ]
  • [ 1097945-22-6 ]
YieldReaction ConditionsOperation in experiment
88.5% In methanol at 64℃; for 0.333333h; 2 EXAMPLE 2 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine methanesulfonate EXAMPLE 2 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine methanesulfonate (0049) Heat a slurry of 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine (500 mg, 0.976 mmol) in methanol (2.5 mL) to 64°C. Add a solution of methanesulfonic acid (64 µL, 0.976 mmol) in methanol (1.0 mL) over 5 minutes. Stir the mixture at 64°C for 15 minutes and then add isopropanol (5.0 mL) over 30 minutes. Allow the resulting slurry to cool to room temperature over 1 hour and then stir at room temperature for 4 hours. Filter the slurry, wash with isopropanol, and dry under reduced pressure at 42°C to provide the title compound as an orange solid (478 mg, 88.5% (adjusted for 9.9% volatiles in starting material and 1.0% volatiles in product)). m.p. = 282.3°C (DSC)
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