Home Cart 0 Sign in  

[ CAS No. 871700-17-3 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 871700-17-3
Chemical Structure| 871700-17-3
Structure of 871700-17-3 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 871700-17-3 ]

Related Doc. of [ 871700-17-3 ]

Alternatived Products of [ 871700-17-3 ]

Product Details of [ 871700-17-3 ]

CAS No. :871700-17-3 MDL No. :MFCD17215075
Formula : C26H23FIN5O4 Boiling Point : -
Linear Structure Formula :- InChI Key :LIRYPHYGHXZJBZ-UHFFFAOYSA-N
M.W : 615.39 Pubchem ID :11707110
Synonyms :
JTP-74057;GSK1120212;Trametinib. Brand name: Mekinist.;GSK 1120212 GSK1120212

Calculated chemistry of [ 871700-17-3 ]

Physicochemical Properties

Num. heavy atoms : 37
Num. arom. heavy atoms : 22
Fraction Csp3 : 0.23
Num. rotatable bonds : 6
Num. H-bond acceptors : 5.0
Num. H-bond donors : 2.0
Molar Refractivity : 149.59
TPSA : 107.13 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -7.62 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.68
Log Po/w (XLOGP3) : 3.43
Log Po/w (WLOGP) : 4.11
Log Po/w (MLOGP) : 4.21
Log Po/w (SILICOS-IT) : 3.95
Consensus Log Po/w : 3.87

Druglikeness

Lipinski : 2.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.17

Water Solubility

Log S (ESOL) : -5.86
Solubility : 0.000849 mg/ml ; 0.00000138 mol/l
Class : Moderately soluble
Log S (Ali) : -5.36
Solubility : 0.00268 mg/ml ; 0.00000436 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -7.96
Solubility : 0.00000683 mg/ml ; 0.0000000111 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.99

Safety of [ 871700-17-3 ]

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 [ 871700-17-3 ]

* 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 [ 871700-17-3 ]

[ 871700-17-3 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 871700-17-3 ]
  • [ 1066-54-2 ]
  • [ 871700-35-5 ]
YieldReaction ConditionsOperation in experiment
93% With triethylamine In chloroform at 20℃; for 20h; 4-3.1 Under a nitrogen atmosphere, to N-{3-[3-cyclopropyl-5-(2- fluoro-4-iodophenylamino) -6,8-dimethyl-2,4,7-trioxo-3,4,6,7- tetrahydro-2H-pyrido[4,3-d]pyrimidin-l-yl]phenyl}acetamide 59 (14.5 g) obtained in Example 4-1 were added chloroform (145 ml), trimethylsilylacetylene 60 (4.99 ml) and triethylamine (13.1 ml). Copper (I) iodide (22 mg) and bis (triphenylphosphine)palladium(II)chloride (83 mg) were added, and the mixture was stirred at room temperature for 20 hrs. The mixture was concentrated under reduced pressure, activated carbon (435 mg) and methanol (435 ml) were added to the residue, and the mixture was stirred with heating at reflux for 2 hrs. Activated carbon was filtered off while it was hot, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:acetone=10:1-4:1) and toluene- acetone [5: 1 (volume ratio), 87 ml] was added to the obtained crystals. The mixture was stirred at 80°C for 1 hr. After allowing to cool to room temperature, the crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro- 4-trimethylsilanylethynylphenylamino) -6,8-dimethyl-2,4,7-trioxo- 3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-l- yl] phenyl}acetamide 61 (12.9 g, yield 93%) as pale-yellow crystals.
  • 2
  • [ 871700-25-3 ]
  • [ 871700-17-3 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-ylamino]phenyl}acetamide With sodium methoxide In tetrahydrofuran; methanol at 20℃; for 4h; Stage #2: With glacial acetic acid In tetrahydrofuran; methanol at 20℃; for 0.5h; 4-1.8 Under a nitrogen atmosphere, to a solution (1.57 g) of 28% sodium methoxide in methanol was added tetrahydrofuran (40 ml), N-{3-[3-cyclopropyl-l-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7- trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5- ylamino] phenyl}acetamide 58 (5.00 g) obtained in Step 7 was added, and the mixture was stirred at room temperature for 4 hrs. Acetic acid (0.56 ml) was added, and the mixture was stirred at room temperature for 30 min. Water (40 ml) was added and the mixture was further stirred for 1 hr. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro-4- iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H- pyrido[4,3-d]pyrimidin-l-yl]phenyl}acetamide 59 (4.75 g, yield 95%) as colorless crystals. MS ESI m/e: 616 (M+H), 614 (M-H). (at)H-NMR(DMSO-d6, 400MHz) No. 0.63-0.70 (m, 0.91-1.00 (m, 2H),1.25(s, 3H) , 2.04(s, 3H) , 2.58-2.66 (m, 1H), 3.07(s, 3H) , 6.92 (t, J=8.8Hz, 1H), 7.00-7.05 (m, 1H), 7.36 (t, J=8.2Hz, 1H), 7.52-7.63(m, 3H), 7.79 (dd, 10.4Hz, 1H), 10.10(s, 1H), 11.08 (s, 1H).
95% With sodium methoxide
81.2% With methanol; sodium methoxide In tetrahydrofuran at 5 - 20℃; for 2h; Inert atmosphere; 2.9 (9). Preparation of compounds 2-9: Under nitrogen protection, a solution of sodium methoxide in methanol (4 mL, 30%, 22.2 mmol) was added dropwise to a solution of compound 2-8 (1.5 g, 2.44 mmol) in tetrahydrofuran (20 mL) at 5°C. After the dropwise addition was completed, the reaction solution was slowly warmed to room temperature and continued to be stirred for 2 hours. After completion of the reaction, water (100 mL) was added to the reaction solution, followed by extraction with ethyl acetate (100 mL×2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol=80/1) to obtain 1.2 g of white solid 2-9 in a yield of 81.2%.
Stage #1: N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-ylamino]phenyl}acetamide With sodium methoxide In tetrahydrofuran; methanol at 20℃; for 4h; Stage #2: With glacial acetic acid In tetrahydrofuran; methanol at 20℃; for 0.5h; 4-1.9 Under a nitrogen atmosphere, to N-{3-[3-cyclopropyl-l-(2- fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8- hexahydro-pyrido [2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide 58 (45.7 g) was added tetrahydrofuran (366 ml), and a solution (15.7 g) of 28% sodium methoxide in methanol was added dropwise with stirring at room temperature and the mixture was stirred at room temperature for 4 hrs. Acetic acid (5.61 ml) was added, and the mixture was stirred at room temperature for 30 min. With stirring at 70°C in an oil bath, water (366 ml) was added dropwise, and the mixture was stirred for 1 hr. After allowing to cool with stirring, the crystals were collected by filtration and dried to give crystal 1 (46.0 g) of N-{3-[3-cyclopropyl-5-(2-fluoro-4- iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro- 2H-pyrido[4,3-d]pyrimidin-l-yl]-phenyl}-acetamide 59. N, N-Dimethylacetamide (184 ml) was added to crystal 1 (46.0 g), and the mixture was stirred with heating at 130°C. After complete dissolution, the solution was filtered by suction using with paper (5B), and washed with N, N-dimethylacetamide (92.0 ml). The filtrate was stirred under heating at 130°C, 1-butanol (138 ml) and water (96.0 ml) were successively added dropwise, and the mixture was stirred for 30 min. Water (46.0 ml) was further added dropwise, and the mixture was stirred for 30 min allowed to cool with stirring. The crystals were collected by filtration and dried to give crystal 2 (41.7 g) of N-{3-[3-cyclopropyl-5-(2- fluoro-4-iodo-phenylamino) -6,8-dimethyl-2,4,7-trioxo-3,4,6,7- tetrahydro-2H-pyrido[4,3-d]pyrimidin-l-yl]-phenyl}-acetamide 59 as colorless crystals. To crystal 2 (41.5 g) was added 1-butanol-water [19:1 (volume ratio), 415 ml], and the mixture was stirred at 130°C for 18 hrs. After allowing to cool with stirring, the crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5- (2-fluoro-4-iodo-phenylamino) -6,8-dimethyl-2,4,7-trioxo-3,4,6,7- tetrahydro-2H-pyrido[4,3-d]pyrimidin-l-yl]-phenyl}-acetamide 59 (40.7 g, yield 89%) as colorless crystals.
4.75 g With sodium methoxide In tetrahydrofuran; methanol at 20℃; for 4h; Inert atmosphere; 1 Under a nitrogen atmosphere, tetrahydrofuran (40 mE) was added to N-{3-[3-cyclopropyl- 1 -(2-fluoro-4-iodo- phenyl)-6,8-dimethyl-2,4,7-trioxo-1 ,2,3,4,7,8-hexahydro- pyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide (5 g) and a methanol solution (1.57 g) containing 28% sodium methoxide was added and the mixture was stirred at room temperature for 4 hours. Acetic acid (0.56 mE) was added to the mixture and the mixture was stirred at room temperature for 30 mm. And then water (40 mE) was added and the mixture was further stirred for 1 hout The crystals were collected by filtration and dried under reduced pressure at 40° C. to give trametinib (4.75 g). Its HPEC content ofA impurity is 0.42 wt %.

  • 3
  • [ 10273-89-9 ]
  • [ 871700-17-3 ]
  • [ 2236567-28-3 ]
YieldReaction ConditionsOperation in experiment
84% With C17H24N5Ru(1+)*F6P(1-); potassium acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 35℃; for 24h; Inert atmosphere;
84% With C17H24N5Ru(1+)*F6P(1-); potassium acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 35℃; for 24h; Inert atmosphere; Glovebox; General Procedure C: arylation of DG-containing (hetero)arenes with (hetero)aryl (pseudo)halides using cyclometalated ruthenium(ll) catalysts General procedure: Unless otherwise stated, in an Argon filled glove-box a crimp-cap microwave vial equipped with a magnetic stirring bar was charged with the appropriate cyclometalated Ru(ll)-catalyst (like Ru1-Ru46, from 3 mol % to 10 mol %), KOAc (5.9 mg, 0.06 mmol, 30 mol %), K2CO3 (2.0 - 4.0 equiv.), the appropriate DG-containing arene (like N1-N12, 0.20 mmol, 1.0 equiv.), the appropriate (hetero)aryl (pseudo)halide (like X1-X42, 0.2 mmol, 1.0 equiv) and /V-methyl-2- pyrrolidone (NMP) (200 pL, 1 M). The vial was capped and stirred at 35 °C for 24 hours. Upon completion, the crude mixture was loaded on a silica gel column and purified by flash chromatography.
  • 4
  • trametinib [ No CAS ]
  • [ 198904-31-3 ]
  • C90H96F2N16O15 [ No CAS ]
  • 5
  • [ 871701-87-0 ]
  • [ 871700-17-3 ]
YieldReaction ConditionsOperation in experiment
44.8% With pyridine; acetic anhydride In chloroform at 0 - 20℃; for 2h; 1.3; 2.3; 3.3 At 0 ° C,Compound 9 (10 g, 17.4 mmol)Pyridine (100 mL) and chloroform (200 mL)Acetic anhydride (2 mL, 20.9 mmol) was added to the suspension.Stir at room temperature for 2 h,The mixture was poured into dilute hydrochloric acid (1 mol/L, 500 mL).Liquid separation,The water layer was treated with chloroform (150 mL at a time,A total of two) extraction,Combine the organic layers,Washed with saturated brine (200 mL),dry,concentrate,Ethyl acetate was recrystallized twice.White powder trimetinib (4.8g),The yield was 44.8%.
  • 6
  • [ 871700-17-3 ]
  • [ 2817714-75-1 ]
YieldReaction ConditionsOperation in experiment
81% With Lawessons reagent In 1,4-dioxane at 100℃; for 2h; Inert atmosphere; 2.10 (10). Preparation of compound 2: Under nitrogen protection, compound 2-9 (615 mg, 1.0 mmol) and Lawson's reagent (1.21 g, 3.0 mmol) were dissolved in 1,4-dioxane (10 mL) and stirred at 100° C for 2 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and ethyl acetate (100 mL) was added. The organic phase was washed successively with saturated aqueous sodium bicarbonate solution (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 3/1) to obtain 510 mg of product 2 as a pale yellow solid in a yield of 81%.
Same Skeleton Products
Historical Records