Home Cart 0 Sign in  

[ CAS No. 459868-92-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 459868-92-9
Chemical Structure| 459868-92-9
Structure of 459868-92-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 459868-92-9 ]

Related Doc. of [ 459868-92-9 ]

Alternatived Products of [ 459868-92-9 ]

Product Details of [ 459868-92-9 ]

CAS No. :459868-92-9 MDL No. :MFCD17010269
Formula : C19H21FN3O5P Boiling Point : -
Linear Structure Formula :- InChI Key :FCCGJTKEKXUBFZ-UHFFFAOYSA-N
M.W : 421.36 Pubchem ID :9931953
Synonyms :
PF-01367338 phosphate;AG-014699 phosphate;PF-01367338;AG-014699;Rucaparib (phosphate)

Calculated chemistry of [ 459868-92-9 ]

Physicochemical Properties

Num. heavy atoms : 29
Num. arom. heavy atoms : 15
Fraction Csp3 : 0.21
Num. rotatable bonds : 3
Num. H-bond acceptors : 7.0
Num. H-bond donors : 6.0
Molar Refractivity : 110.29
TPSA : 144.49 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -10.21 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.66
Log Po/w (XLOGP3) : -1.88
Log Po/w (WLOGP) : 1.94
Log Po/w (MLOGP) : 0.92
Log Po/w (SILICOS-IT) : 4.65
Consensus Log Po/w : 1.46

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.45
Solubility : 14.9 mg/ml ; 0.0353 mol/l
Class : Very soluble
Log S (Ali) : -0.63
Solubility : 97.7 mg/ml ; 0.232 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -7.67
Solubility : 0.00000899 mg/ml ; 0.0000000213 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.19

Safety of [ 459868-92-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338-P310 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 459868-92-9 ]

* 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.

  • Downstream synthetic route of [ 459868-92-9 ]

[ 459868-92-9 ] Synthesis Path-Downstream   1~10

YieldReaction ConditionsOperation in experiment
58%
  • 2
  • [ 459868-92-9 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
at 40℃; for 4383h; 75 % relative humidity; 5 Polymorphic Form V of Compound I was formed during the stability studies of Form Il when stored at 4O0C under 75% relative humidity for 6 months period. Polymorphic Form V of Compound I is physically and chemically stable at room temperature for at least 3 months. Polymorphic Form V of Compound I has an aqueous solubility of 3.0 mg/mL at pH 5.4.Figure 13 provides an X-ray powder diffraction pattern of Form V. Figure 16 is an infrared absorption spectrum of polymorphic Form V of Compound I. The DSC thermogram for Form V has an endotherm at 199.40°C, with two desolvation peaks at 57.290C and 110.73°C, respectively (Figure 17).
  • 3
  • 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one phosphate [ No CAS ]
  • [ 283173-50-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; acetone; at 30℃; for 1.5h; 5.0 g of Rucaparib Phosphate Form III was suspended in 150 ml acetone:water mixture (1 :2). Suspension is heated up to 30°C and 1.05 eq of 20percent sodium hydroxide solution was gradually added. Suspension was stirred for 1.5 hour and then filtrated off. The obtained product was analyzed by XRD, indicating that Form I was obtained. Product was further dried at 40- 60°C under vacuum until constant mass. The dried product was analyzed by XRD, indicating that Form II was obtained. The XRD pattern is presented in Figure 35.
  • 4
  • [ 459868-92-9 ]
  • [ 1609108-45-3 ]
  • [ 2362536-77-2 ]
YieldReaction ConditionsOperation in experiment
80% With pyridine; benzotriazol-1-ol In N,N-dimethyl-formamide at 20℃; for 16h; Molecular sieve; Intermediate III-4: [(2R)-2-(2-pyridyldisulfanyl)propyl] N-[[4-(6-fluoro-3,10- diazatricyclo [6.4.1.04,13] trideca- 1,4,6, 8(13)-tetraen-2-yl)phenyl] methyl] -N-methyl- carbamate To a mixture of HOBt (48.0 mg, 0.31 mmol), pyridine (0.11 mL, 1.31 mmol), finely ground molecular sieve 4 A (250 mg), and the 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3.10-diazatricyclo[6.4. l.04,l3]trideca-l,4,6,8(l3)-tetraen-9-one phosphate (110 mg, 0.26 mmol) in 5 mL of anhydrous DMF was added the (4-nitrophenyl) [(2R)-2-(2- pyridyldisulfanyl)propyl] carbonate [Intermediate II-4] (105 mg, 0.29 mmol). After stirring for 16 h at room temperature, the molecular sieves were filtered off and the solvent removed in vacuo. The residue was then adsorbed onto S1O2 and purified by column chromatography (S1O2, 0-10% MeOH/CLhCh) to afford [(2R)-2-(2-pyridyldisulfanyl)propyl] N-[[4-(6-fluoro-3.10-diazatricyclo[6.4.l.04,l3]trideca-l,4,6,8(l3)-tetraen-2-yl)phenyl]methyl]-N-methyl- carbamate (115 mg, 80% yield) MS m/z 551.1 (M+H)+.
  • 5
  • [ 459868-92-9 ]
  • [ 2362536-70-5 ]
  • [ 2362537-15-1 ]
YieldReaction ConditionsOperation in experiment
75.4% With dmap; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 16h; Inert atmosphere; Intermediate XXI-1: [4-[2-(2-pyridyldisulfanyl) ethoxycarbonylamino] phenyl]methyl N-[[4-(6-fluoro-9-oxo-3,10-diazatricyclo[6.4.1.04,13]trideca-l,4(13),5,7-tetraen-2- yl)phenyl] methyl] -N-methyl-carbamate To 2-[4-(methylaminomethyl)phenyl]-3,l0-diazatricyclo[6.4. l.04,l3]trideca- 1,4(13), 5, 7-tetraen-9-one;phosphoric acid (36.0 mg, 0.09 mmol) in 2 mL of dry DMF under N2was added DIPEA (0.03 mL, 0.18 mmol), DMAP (10.9 mg, 0.09 mmol) and (4- nitrophenyl) [4-[2-(2-pyridyldisulfanyl)ethoxycarbonyl amino] phenyl]methyl carbonate (44.8 mg, 0.09 mmol). The mixture was stirred for 16 h. The mixture was diluted with 20 ml of EtOAc, washed with 1x20 mL of sat. NFLCl, 2x20 mL of sat. NaHCCh, 3x30 mL of FLO and 1x20 mL of sat. brine. The mixture was dried with MgSCri. filtered and concentrated. The crude residue was purified by column chromatography (SiC , 0-5% MeOH/CThCh) to give [4-[2-(2-pyridyldisulfanyl) ethoxy carbonylamino] phenyl] methyl N-[[4-(6-fluoro-9-oxo- 3, l0-diazatricyclo[6.4.1.04,13] trideca-l,4(l3),5,7-tetraen-2-yl)phenyl]methyl]-N-methyl- carbamate (44.2 mg, 0.06 mmol, yield: 75.4 %).
  • 6
  • 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one phosphate [ No CAS ]
  • [ 1151989-04-6 ]
  • [4-(2-pyridyldisulfanyl)phenyl]methyl N-[(4-{6-fluoro-9-oxo-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-2-yl}phenyl)methyl]-N-methylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With benzotriazol-1-ol; triethylamine; In tetrahydrofuran; at 20℃; for 16.0h;Inert atmosphere; To a stirred solution of 2-[4-(methylaminomethyl)phenyl]-3,l0- diazatricyclo[6.4.1.04,13] trideca-l,4(l3),5,7-tetraen-9-one;phosphoric acid (1.00 g, 3.09 mmol) in THF (20 mL) under N2 was added TEA (1.40 mL, 3.04 mmol), HOBt (0.21 g, 1.50 mmol) and 4-nitrophenyl (4-(pyridin-2-yldisulfaneyl)benzyl) carbonate (1.40 g, 3.40 mmol). The mixture was stirred under N2 for 16 h at room temperature. The reaction mixture was concentrated and the crude purified by flash chromatography (S1O2, 0-5% MeOH/CTBCh to afford [4-(2-pyridyldisulfanyl)phenyl]methyl N-[[4-(6-fluoro-9-oxo-3,l0- diazatricyclo[6.4.1.04,13] trideca-l,4,6,8(l3)-tetraen-2-yl)phenyl]methyl]-N-methyl- carbamate as a colourless solid (1.13 g, 59% yield). MS m/z 599.0 (M+H)+.
  • 7
  • [ 459868-92-9 ]
  • [ 2362536-75-0 ]
  • [ 2362537-27-5 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol In N,N-dimethyl-formamide at 20℃; for 16h; Molecular sieve; Synthesis of XLVII- 1: Methyl (2S,3S,4S,5R,6S)-3,4,5-triacetoxy-6-[3-R10-2-Rll-4-[[[4- (6-fluoro-9-oxo-3,10-diazatricyclo[6.4.L04,13]trideca-l,4,6,8(13)-tetraen-2- yl)phenyl] methyl-methyl-carbamoyl] oxymethyl] -6- [3-(2- pyridyldisulfanyl)propanoylamino]phenoxy]tetrahydropyran-2-carboxylate To a mixture of l-hydroxybenzotriazole hydrate (13.0 mg, 0.0851 mmol), finely ground molecular sieve 4 A (100 mg), and 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,l0- diazatricyclo[6.4. l.04,l3]trideca-l,4,6,8(l3)-tetraen-9-one;phosphoric acid (35.9 mg, 0.0851 mmol) in 2 mL of anhydrous DMF was added methyl (2S,3S,4S,5R)-3,4,5-triacetoxy-6-[4- [(4-nitrophenoxy)carbonyloxymethyl]-2-[3-(2- pyridyldisulfanyl)propanoylamino]phenoxy]tetrahydropyran-2-carboxylate (58.0 mg, 0.0709 mmol). After stirring for 16 h at room temperature, the molecular sieve was filtered off and the solvent was removed in vacuo. The reaction mixture was diluted with EtOAc, washed with sat. NH4CI, water and brine. The organic layer was dried with NaSOr and concentrated. The crude residue was purified by column chromatography (0-3% MeOH/DCM) to give 35 mg of methyl (2S,3S,4S,5R)-3,4,5-triacetoxy-6-[4-[[[4-(6-fluoro-9-oxo-3,l0- diazatricyclo[6.4. l.04,l3]trideca-l,4,6,8(l3)-tetraen-2-yl)phenyl]methyl-methyl- carbamoyl]oxymethyl]-2-[3-(2-pyridyldisulfanyl)propanoylamino]phenoxy]tetrahydropyran- 2-carboxylate (43.0 mg, 0.0429 mmol, yield: 60.5 %) with a slight unknown impurity. MS m/z 1002.1 (M+H)+.
  • 8
  • [ 459868-92-9 ]
  • [ 2362537-24-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 65 °C 2.1: hydrogenchloride / 1,4-dioxane; dichloromethane; water / 20 °C
  • 9
  • [ 459868-92-9 ]
  • [ 2362537-26-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 65 °C 2.1: hydrogenchloride / 1,4-dioxane; dichloromethane; water / 20 °C 3.1: dmap; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h
  • 10
  • 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one phosphate [ No CAS ]
  • [ 14296-92-5 ]
  • [1-[2-(tert-butoxycarbonylamino)acetyl]pyrrolidin-2-yl] N-[[4-(6-fluoro-9-oxo-3,10-diazatricyclo[6.4. 1.04,13]trideca-1,4,6,8(13)-tetraen-2-yl)phenyl]methyl]-N-methylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
141 mg l-[2-(tert-Butoxycarbonylamino)acetyl]pyrrolidine-2-carboxylic acid (0.16 g, 0.59 mmol) was dissolved in DMF and to it was added l-hydroxybenzotriazole hydrate (80.0 %, 114 mg, 0.59 mmol) and EDC HC1 (114 mg, 0.59 mmol). The solution was stirred at RT for 15 min before the 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,l0- diazatricyclo[6.4. l.04,l3]trideca-l,4,6,8(l3)-tetraen-9-one;phosphoric acid (200 mg, 0.475 mmol) and N,N-diisopropylethylamine (0.44 mL, 2.37 mmol) were added. The solution was then heated to 65 C overnight. LC-MS indicated a complete reaction. The reaction mixture was diluted with EtOAc, washed with sat. NEECl, water, and brine. The crude [l-[2-(tert- butoxycarbonylamino)acetyl]pyrrolidin-2-yl] N-[[4-(6-fluoro-9-oxo-3,l0- diazatricyclo[6.4. l.04,l3]trideca-l,4,6,8(l3)-tetraen-2-yl)phenyl]methyl]-N-methyl- carbamate (141 mg, 0.24 mmol, yield: 50.0 %) was carried on as is. MS m/z 478.2 (M+H minus BOC)+.
Same Skeleton Products
Historical Records

Similar Product of
[ 459868-92-9 ]

Chemical Structure| 283173-50-2

A115210[ 283173-50-2 ]

8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one

Reason: Free-salt