Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
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)
|
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 |
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 |
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 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 1.0 |
Egan : | 1.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
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 |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 3.19 |
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: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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)+. |
Yield | Reaction Conditions | Operation 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 %). |
Yield | Reaction Conditions | Operation 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)+. |
Yield | Reaction Conditions | Operation 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)+. |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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)+. |
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