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[ CAS No. 868540-16-3 ] {[proInfo.proName]}

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Chemical Structure| 868540-16-3
Chemical Structure| 868540-16-3
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Product Details of [ 868540-16-3 ]

CAS No. :868540-16-3 MDL No. :MFCD28137654
Formula : C31H42N4O6 Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W : 566.69 Pubchem ID :-
Synonyms :

Safety of [ 868540-16-3 ]

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 [ 868540-16-3 ]

* 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 [ 868540-16-3 ]

[ 868540-16-3 ] Synthesis Path-Downstream   1~52

  • 1
  • [ 868540-16-3 ]
  • [ 247068-84-4 ]
  • carfilzomib [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0 - 5℃; To a stirred solution of (F) [see: Bioorg. Med. Chem. Letter 1999, 9, 2283-88] (1.3 eq., 0.27 mmol, 0.083 mg) in MeCN (5 mL) was added (W) (1 eq., 0.17 mmol, 0.10 g), DIEA (10 eq., 1.73 mmol, 0.30 mL) and HOBT (1.6 eq., 0.27 mmol, 0.037 mg). The mixture was cooled to 0 C. in an ice bath and PyBOP (1.6 eq., 0.27 mmol, 0.14 g) was added in several portions. The mixture was stirred at 5 C. under an atmosphere of argon overnight after which, the reaction was diluted with sat. NaCl and extracted with EtOAc. The organic layer was washed with water and brine and dried over anhydrous MgSO4 and concentrated to a paste. The crude material was dissolved in a minimum amount of MeOH and slowly added to rapidly stirred, 0 C. chilled water (100 mL). Compound 6 was then isolated by filtration (0.080 g).
  • 2
  • [ 875309-92-5 ]
  • [ 868540-16-3 ]
YieldReaction ConditionsOperation in experiment
With methanol; hydrogen;palladium 10% on activated carbon; In ethyl acetate; under 760.051 Torr; for 2h; Compound (V) (0.25 g, 0.39 mmol) was mixed with 12 mL of TFA/DCM (80%) and was stirred at room temperature for 1 hr at which time the mixture was concentrated and placed under high vacuum for 2 hr giving the TFA salt of the tri-peptide amine. The crude amine salt was dissolved in 6 mL DMF and 2-morpholino acetic acid (0.074 g, 0.507 mmol) was added followed by DIEA (0.504 g, 0.68 mL, 3.90 mmol). The mixture was cooled to 0 C. in an ice bath and PyBOP (0.32 g, 0.62 mmol) was added and stirred under an atmosphere of argon while warming to room temperature overnight. The mixture was diluted with brine (50 mL) and extracted with EtOAc (5×20 mL). The organic layers were combined, washed with sat. NaHCO3 (5×15 mL) and brine (1×25 mL) and dried over MgSO4. The MgSO4 was removed by filtration and the volatiles removed under reduced pressure to give the intermediate ester (0.195 g). To (0.150g, 0.23 mmol) of the intermediate ester was added 10% Pd/C (0.05g) followed by 5 mL of 1:1 mixture of MeOH and EtOAc and the mixture was placed under an atmosphere of hydrogen. After 2 hr, the contents were filtered through a plug of Celite and concentrated under vacuum to give (W) (0.12 g).
77 g With palladium on activated charcoal; ammonium formate; In methanol; at 25 - 30℃; for 2h; EXAMPLE 7: Preparation of compound of Formula XV Compound of Formula XIV (lOOg) was dissolved in methanol (4.51it) at 25-30C. To the reaction mass ammonium formate (38.5g dissolved in 500ml methanol) and palladium on carbon (20 g) were added and stirred for 2 hr at same temperature. After completion of the reaction, filtered the reaction mass and filterate was distilled under vacuum at below 45 C to obtain residue. To the obtained residue water (Hit) was added at 25-30C and stirred for 2-3 hr at same temperature. The solid was filtered, washed with acetone (500 ml) and dried. To the obtained solid n-propanol (31it) was added and heated to reflux for lhr. Then the reaction mass was allowed to cool to 25-30C and stirred for 2-4 hr at same temperature. Precipitated solid was filtered, washed with n-propanol (200 ml) and dried to get the title compound. Yield: 77g; Chemical purity by HPLC: 99.7%.
  • 3
  • [ 868540-16-3 ]
  • (2R,4S)-4-((tert-butoxycarbonyl)amino)-2-hydroxy-2,6-dimethyl-3-oxoheptyl 3-(prop-2-yn-1-yloxy)propane-1-sulfonate [ No CAS ]
  • [ 1541172-80-8 ]
YieldReaction ConditionsOperation in experiment
80% Referring to FIG. 39, (2R,4S)-4-((tert-butoxycarbonyl)amino)-2-hydroxy-2,6-dimethyl-3 -oxoheptyl 3 -Qrop-2-yn- I -yloxy)propane- 1 -sulfonate (4.13 g, 0.00854 mol)and 4N hydrogen chloride in dioxane (50 mL) were stirred at room temperature for 1 hour and then evaporated to dryness. (S)-2-((S)-4-methyl-2-((S)-2-(2- morpholinoacetamido)-4-phenylbutanamido)pentanamido)-3 -phenyipropanoic acid (4.84 g, 0.00854 mol), HBTU (4.86 g, 0.0128 mol), HOBt (1.73 g, 0.0128 mol) and DMF (50mL) were added to the residue and stirred until dissolved. The reaction was cooled to 0C and D1EA (4.46 mL, 0.0256 mol) added dropwise. The mixture was stirred at 0 C for30 minutes, diluted with 2N HC1, and extracted with ethyl acetate. The extract waswashed with sat. aq. sodium bicarbonate, brine, dried (MgSO4) and evaporated. Theresidue was purified by Biotage flash column chromatography (5% MeOH/30%EtOAc/DCM) to give product 13 as a foam (6.4 g, 80%).
  • 4
  • [ 868540-16-3 ]
  • (S)-2-amino-4-methyl-1-((R)-2-methyloxiran-2-yl)pentan-1-one trifluoroacetic acid salt [ No CAS ]
  • (x)C6H8O7*C40H57N5O7 [ No CAS ]
  • 5
  • [ 868540-16-3 ]
  • (S)-2-amino-4-methyl-1-((R)-2-methyloxiran-2-yl)pentan-1-one trifluoroacetic acid salt [ No CAS ]
  • carfilzomib [ No CAS ]
YieldReaction ConditionsOperation in experiment
230 g With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 5℃; for 1.5h; A flask equipped with a mechanical stirrer, thermocouple, cooling bath, nitrogen inlet and drying tube wascharged with DMF, (F) (133.9 g), (E) (241.8 g), HBTU (242.8 g), and HOBT (86.5 g) and the mixture was stirred andcooled to 0-5 C. DIEA (156 mL) was then added slowly over at least 30 minutes, while maintaining temperature between0-5 C. The reaction mixture was stirred at 0-5 C for one hour and was then poured into a vigorously stirred saturatedsolution of sodium bicarbonate (3630 mL) and ethyl acetate (900 mL). Additional ethyl acetate (2000 mL) was added toextract the product and the organic layer was separated. The aqueous layer was then extracted with ethyl acetate (1930mL). The organic phases were combined and washed with saturated solution of sodium bicarbonate (2420 mL) andbrine (2420 mL), dried over magnesium sulfate (360 g), filtered through glass fiber filter and rinsed with ethyl acetate (2x 360 mL). The resulting solution was concentrated to a semisolid under reduced pressure and methanol (725 mL) wasadded and co-evaporated under reduced pressure to yield semisolid compound 1. The crude product was dissolved inmethanol (5320 mL) and the solution was stirred while water (2130 mL) was added over twenty minutes. When additionof water was complete, approximately 0.3 g of pure crystalline seeds were added and the methanol/water solution wasstirred for three hours. The resulting crystalline white solid was isolated by filtration and the fine white crystalline productwas rinsed with a methanol/water solution (1:1, 1200 mL). The resulting solid was rinsed with methanol/water solution(1:1, 1200 mL) and the crystalline product was poured onto drying tray and dried to a constant weight under high vacuumat 27 C under nitrogen bleed to yield crystalline compound 1 (230 g).
100.0 g With 4-methyl-morpholine; benzotriazol-1-ol; HATU; In N,N-dimethyl-formamide; at 0 - 5℃; for 3h;Inert atmosphere; Example-30: Preparation of compound of formula-1 (S)-2- Amino-4-methyl- 1 -((R)-2-methyloxiran-2-yl)pentan- 1 -one trifluoroacetic acid salt compound of formula-4a (47 gm) was added to a pre-cooled solution of (S)-2-((S)-4- methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamido)-3-phenyl propanoic acid compound of formula-2 (100 gm) and N,N-dimethylformamide (1000 ml) at 0-5C under nitrogen atmosphere. l-[bis(dimethylamino)methylene]-lH-l,2,3-triazolo[4,5- b]pyridinium 3-oxid hexafluoro phosphate (74 gm), hydroxybenzotriazole (4 gm) and N- methylmorpholine (38.4 ml) were added to the reaction mixture at 0-5C and stirred for 3 hrs at the same temperature. Aqueous sodium bicarbonate solution and ethyl acetate were added to the reaction mixture at 10-15C and stirred for 10 min at the same temperature. Both the organic and aqueous layers were separated and extracted the aqueous layer with ethyl acetate. Combined the organic layers and washed with water. Distilled off the solvent completely from the organic layer under reduced pressure. Methanol (800 ml) was added to the obtained compound at 25-30C. Heated the reaction mixture to 55-60C and water (800 ml) was added at the same temperature. Cooled the reaction mixture to 25-30C and stirred for 2 hrs at the same temperature. Filtered the precipitated solid, washed with water and then dried the material to get pure title compound. Yield: 100.0 gm.
0.08 g With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0 - 5℃;Inert atmosphere; COMPARATIVE EXAMPLE 5: Preparation of carfilzomib Trifluoroacetic acid salt of Formula IX (0.08g), acetonitrile (5 ml), compound of Formula XV (Olg, leq), diisopropyl ethyl amine (0.3g) and HOBt (0.04g, 1.6eq) were combined in a reaction flask at 25-30C. Reaction mass was allowed to cool to 0C and PyBOP (0.15g, 1.6eq) was added lot wise in 5 min at same temperature. Then the reaction mass was stirred for overnight under nitrogen at 5C. After completion of reaction, reaction mass was diluted with brine solution and extracted with ethyl acetate and the organic layer was washed with saturated sodium bicarbonate solution, water followed by sodium chloride solution. Organic layer was separated and distilled under vacuum and the obtained crude compound was dissolved in methanol and slowly added in to water (100ml) under rapid stirring at 0C. Precipitated solid was filtered to get the title compound. Yield: 0.08 g; Chemical purity by HPLC: 25.91%; HOBt: 59.34%, PyBOP: 2.04% and tris(pyrrolidino phosphine) oxide: 1.7% by HPLC.
  • 9
  • [ 868540-16-3 ]
  • C9H17NO2*CH2O2 [ No CAS ]
  • (x)C6H8O7*C40H57N5O7 [ No CAS ]
  • 10
  • [ 868540-16-3 ]
  • C9H17NO2*CH2O2 [ No CAS ]
  • carfilzomib [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; at 0℃; for 1h; To a 10 mL round bottomed flask containing (S) was added (E) (0.085 g, 0.15 mmol), MeCN (2.0 mL), HOBT(0.031 g, 0.23 mmol), HBTU (0.087 g, 0.23 mmol) and the mixture was cooled to 0 C. To this mixture was slowly addedDIEA (0.077 g, 0.104 mL, 0.6 mmol). The mixture was then allowed to stir at 0 C for 60 minutes and was quenched bythe addition of saturated NaHCO3 (5 mL). The mixture was diluted with EtOAc (15 mL) and the layers separated. Theorganic layer was washed with saturated NaHCO3 (3 x 5 mL), brine (2 x 5 mL) and dried over Na2SO4. The Na2SO4was removed by filtration and the volatiles removed under reduced pressure to give a thick oil. To the flask containingthe oil was added DCM (1 mL) and the mixture placed under high vacuum while swirling giving Compound 1 as a foam.
  • 12
  • [ 868540-08-3 ]
  • [ 868540-16-3 ]
  • 13
  • C32H44N4O6 [ No CAS ]
  • [ 868540-16-3 ]
YieldReaction ConditionsOperation in experiment
With lithium hydroxide; In methanol; water; at 0 - 5℃; for 12h; LiOH (0.94 mmol, 0.023 g) was added to a slurry of (D) (0.094 mmol) in 4 mL of 3:1 MeOH/H2O cooled to 0C. After 12 hr at 5 C the reaction was quenched with 20 mL sat. NH4Cl and diluted further with 10 mL H2O. The pH of the reaction mixture was adjusted to 3 with 1N HCl, extracted with DCM (3 x 15 mL), and dried over MgSO4. The MgSO4 was removed by filtration and the volatiles were removed under reduced pressure to give (E).
48.0 g With lithium hydroxide monohydrate; water; In tetrahydrofuran; at 25 - 30℃; for 3h; Hydroxybenzotriazole (4.1 gm) and N-methylmorpholine (31 gm) were added to a pre-cooled mixture of (S)-methyl 2-((S)-2-((S)-2-amino-4-phenylbutanamido)-4- methylpentanamido)-3-phenylpropanoate hydrochloride compound of formula- 12a (75 gm),. 2-morpholinoacetic acid hydrochloride compound of formula- 13a (30.4 gm) and dichloromethane (525 ml) at 0-5C under nitrogen atmosphere. A solution of dicyclohexylcarbodiimide (37.9 gm) in dichloromethane (225 ml) was slowly added to the reaction mixture at 0-5C. Raised the temperature of the reaction mixture to 25-30C and stirred for 2 hrs at the same temperature. Filtered the reaction mixture, cooled the filtrate to 10-15C and washed with aqueous sodium bicarbonate solution followed by with aqueous hydrochloric acid solution and then with water. Distilled off the solvent completely from the reaction mixture under reduced pressure. Tetrahydrofuran (750 ml) and water (375 ml) were added to the obtained solid at 25-30C. Cooled the reaction mixture to 10-15C and aqueous LiOH.H20 solution (12.8 gm of LiOH.H20 dissolved in 75 ml of water) was added. Raised the temperature of the reaction mixture to 25-30C and stirred for 3 hrs at the same temperature. Water and dichloromethane were added to the reaction mixture at 25-30C and stirred for 10 min at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was washed with dichloromethane. Acidified the aqueous layer using aq.hydrochloric acid solution at 25-30C and stirred the reaction mixture for 30 min at the same temperature. Filtered the precipitated solid and washed with water. Methanol (450 ml) was added to the obtained solid at 25-30C. Heated the reaction mixture to 55-60C and stirred for 30 min at the same temperature. Ethanol (225 ml) was added to the reaction mixture at 55-60C and stirred for 45 min at the same temperature. Cooled the reaction mixture to 25-30C and stirred for 1 hr at the same temperature. Filtered the precipitated solid, washed with methanol and then dried the material to get the title compound. Yield: 48.0 gm; M.R: 208-215C.
  • 14
  • [ 6461-07-0 ]
  • [ 868540-16-3 ]
  • 15
  • [ 82732-07-8 ]
  • [ 868540-16-3 ]
  • 16
  • (S)-methyl 2-((S)-2-((S)-2-amino-4-phenyIbutanamido)-4-methylpentanamido)-3-phenylpropanoate hydrochloride [ No CAS ]
  • [ 868540-16-3 ]
  • 17
  • [ 61-90-5 ]
  • [ 868540-16-3 ]
  • 18
  • [ 868540-16-3 ]
  • carfilzomib [ No CAS ]
  • 19
  • [ 868540-16-3 ]
  • [ 771-61-9 ]
  • (S)-perfluorophenyl 2-((S)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamido)-3-phenylpropanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.8 g With 4-methyl-morpholine; HATU; In dichloromethane; at 0 - 5℃; for 6h;Inert atmosphere; l-[bis(dimethylamino)methylene]-lH-l,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU; 1.48 gm) and N-methylmorpholine (0.7 gm) were added to a pre-cooled mixture of (S)-2-((S)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenyl butanamido)pentanamido)-3-phenylpropanoic acid compound of formula-2 (2 gm) and dichloromethane (20 ml) at 0-5C under nitrogen atmosphere. A solution of 2,3,4,5,6- pentafluoro phenol (0.58 gm) in dichloromethane (5 ml) was slowly added to the reaction mixture at 0-5 C and stirred for 6 hrs at the same temperature. Aqueous sodium bicarbonate solution was slowly added to the reaction mixture at 0-5 C and raised the temperature of the reaction mixture to 25-30C. Filtered the reaction mixture, both the organic and aqueous layers were separated from the filtrate and the organic layer was washed with water. Silica gel (10 gm) was added to the organic layer and stirred the reaction mixture for 30 min. Filtered the reaction mixture and washed the silica gel with dichloromethane. Distilled off the solvent completely from the filtrate under reduced pressure. n-Heptane (10 ml) was added to the obtained compound at 25-30C and stirred the reaction mixture for 2 hrs at the same temperature. Filtered the solid, washed with n-heptane and then dried the material to get the tile compound. Yield: 1.8 gm.
  • 20
  • [ 6066-82-6 ]
  • [ 868540-16-3 ]
  • (S)-2,5-dioxopyrrolidin-1-yl 2-((S)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamido)-3-phenylpropanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
26.5 g With diisopropyl-carbodiimide; In dichloromethane; at 0 - 30℃; for 6h;Inert atmosphere; A solution of diisopropyl carbodiimide (6.12 gm) in dichloromethane (75 ml) was slowly added to a mixture of (S)-2-((S)-4-methyl-2-((S)-2-(2-mo holinoacetamido)-4- phenylbutanamido)pentanamido)-3-phenylpropanoic acid compound of formula-2 (25 gm), N-hydroxysuccinimide (5.6 gm) and dichloromethane (250 ml) at 25-30C under nitrogen atmosphere and stirred the reaction mixture for 4 hrs at the same temperature. Cooled the reaction mixture to 0-5C and stirred for 2 hrs at the same temperature. Filtered the reaction mixture and distilled off the solvent completely from the filtrate under reduced pressure to get the title compound as a solid. Yield: 26.5 gm
  • 21
  • [ 7524-50-7 ]
  • [ 868540-16-3 ]
  • 22
  • [ 63-91-2 ]
  • [ 868540-16-3 ]
  • 23
  • [ 868540-16-3 ]
  • [ 110-16-7 ]
  • (S)-2-amino-4-methyl-1-((R)-2-methyloxiran-2-yl)pentan-1-one trifluoroacetic acid salt [ No CAS ]
  • (2S)-N-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran2-yl)-1-oxopentan-2-yl-carbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide maleate salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
100 g EXAMPLE 8: Preparation of carfilzomib maleate salt A mixture of methylene chloride (250 ml) and [(lS)-3-Methyl-l-[[(2R)-2- methyloxiranyl]carbonyl]butyl]carbamic acid 1 , 1 -dimethylethyl ester (50g, leq) was allowed to cool to 2-6C. To the reaction mass trifluoroacetic acid (100ml) was added at same temperature. Then the reaction mass was heated to 25-30C and stirred for 2hr at same temperature. After completion of reaction, reaction mass was distilled completely under vacuum at below 35C and the obtained residue was dissolved in acetonitrile (500 ml). In another reaction flask a mixture of acetonitrile (4500ml) and compound of Formula XV (lOOg, leq) was allowed to cool to -10C to -5C. To the reaction mass HOBt (38.1g, O. leq), PyBOP (146.8g, 1.2eq), acetonitrile solution of (2S)-2-Amino-4-methyl-l-[(2R)-2- methyloxiranyl]-l-pentanonetrifluoroacetate (500 ml) and diisopropyl ethyl amine (91.2ml, 4eq) were added sequentially at -10C to -5C and stirred for 3-4 hr at same temperature. After completion of the reaction, reaction mass was distilled completely under vacuum at below 35C to obtain residue and the obtained residue was dissolved in ethyl acetate and washed the clear solution with 5%sodium bicarbonate (3x100ml), water (Hit), 5% sodium chloride (Hit) sequentially. Organic layer was separated and passed through silica gel bed and the product containing fractions were collected and distilled completely under vacuum at below 35 C to obtain residue. The obtained residue was dissolved in a mixture of acetonitrile (250ml) and tetrahydrofuran (250ml) at 25-30C. To the reaction mass maleic acid (20.5g) was added at 25-30C and stirred for 30min at same temperature. To the reaction mass acetonitrile (500ml) was charged and stirred for 1-2 hr at 25-30C. The solid obtained was filtered, washed with acetonitrile (1.5 lit) and dried. To the obtained compound n-propanol (Hit) was added and heated to reflux for lOmin. Then the reaction mass was allowed to cool to 2-6C. Precipitated solid was filtered, washed with chilled n- propanol (Hit) and dried to get the title compound. Yield: 100 g; PXRD: Fig. 7; Chemical purity by HPLC: 99.8%; HOBt: 0.15%, PyBOP: Not detected and tris(pyrrolidino phosphine) oxide: 0.05% by HPLC.
  • 24
  • (x)C2HF3O2*C22H28N2O3 [ No CAS ]
  • [ 868540-16-3 ]
  • 27
  • [ 868540-16-3 ]
  • C16H21NO5S*ClH [ No CAS ]
  • [ 76-05-1 ]
  • C47H61N5O10S*C2HF3O2 [ No CAS ]
  • 28
  • [ 868540-16-3 ]
  • C12H16F3NO3S*ClH [ No CAS ]
  • [ 76-05-1 ]
  • C43H56F3N5O8S*C2HF3O2 [ No CAS ]
  • 29
  • [ 868540-16-3 ]
  • C12H14F5NO3S*ClH [ No CAS ]
  • [ 76-05-1 ]
  • C43H54F5N5O8S*C2HF3O2 [ No CAS ]
  • 30
  • [ 868540-16-3 ]
  • C16H20FNO5S*ClH [ No CAS ]
  • [ 76-05-1 ]
  • C47H60FN5O10S*C2HF3O2 [ No CAS ]
  • 31
  • [ 868540-16-3 ]
  • L-Leu-[CH2SO2]-DFHMC . HC1 [ No CAS ]
  • [ 76-05-1 ]
  • C47H59F2N5O10S*C2HF3O2 [ No CAS ]
  • 32
  • [ 868540-16-3 ]
  • C12H19NO3S*ClH [ No CAS ]
  • [ 76-05-1 ]
  • C43H59N5O8S*C2HF3O2 [ No CAS ]
  • 33
  • [ 3235-69-6 ]
  • Fmoc-phenylalanine-2-chlorotrityl resin [ No CAS ]
  • [ 35661-60-0 ]
  • [ 132684-59-4 ]
  • [ 868540-16-3 ]
  • 34
  • [ 868540-16-3 ]
  • L-Leu-[CH2SO2]-DFHMC . HC1 [ No CAS ]
  • MorphAc-hPhe-Leu-Phe-W-[CH2SO2]-DFHMC . TFA [ No CAS ]
YieldReaction ConditionsOperation in experiment
47.3% HATU (30.5 mg, 0.080 mmol) was added to a solution of peptidic backbone 11(53.2 mg, 0.080 mmol) in CH2C12 (430 jiL) at 0 C. The reaction mixture was stirred for 20 mmbefore adding sulfonate headgroup 10 (30 mg, 0.073 mmol). Afterwards, the reaction mixture was stirred for 10 mm at 0 C and DIPEA (37 jiL, 0.211 mmol) was added dropwise. The reaction was then allowed to reach RT and was stirred overnight. After evaporation of the solvent the residue was dissolved in DMF (250 jiL). Purification by RP-HPLC (tR = 44 mm, linear gradient 10 - 100% ACN/H20 + 0.1% TFA in 100 mm)and subsequent lyophilization yielded C (35.2 mg, 0.034 mmol, 47.3%) as a white powder. 1H NMR (500 MHz, DMSO-d6): 6 = 10.22 (s, 1H), 8.84 (s, 1H), 8.24 - 8.10 (m, 3H), 7.83 (dd, J 10.5, 2.0 Hz, 1H), 7.31 - 7.26 (m, 2H), 7.21 - 7.14 (m, 6H), 7.14- 7.09 (m, 2H),7.07-6.99 (m, 1H), 6.61 (d, J 1.5 Hz, 1H), 4.52-4.42 (m, 2H), 4.41-4.35 (m, 1H),4.32 (q, J 7.9 Hz, 1H), 4.07-3.66 (m, 8H), 3.36-3.13 (m, 4H), 2.98-2.88 (m, 1H), 2.81-2.70 (m, 1H), 2.64-2.52 (m, 2H), 2.43 (d, J 1.4 Hz, 3H), 1.93- 1.83 (m, 1H), 1.82-1.72 (m, 1H), 1.62 - 1.48 (m, 3H), 1.44 - 1.32 (m, 3H), 0.87 - 0.78 (m, 12H) ppm. 19FNMR (471 MHz, DMSO-d6): 6 = -132.51 (d, J 10.6 Hz), -146.13 ppm. 13C NMR (126MHz, DMSO-d6): 6 = 172.06, 170.87, 170.79, 158.48, 158.27, 158.22, 152.71, 152.06,150.10, 144.10, 141.74, 139.18, 138.16, 129.35, 128.79, 128.69, 128.38, 126.56,126.35, 119.96 (d, J 8.9 Hz), 116.72, 63.52, 56.56, 54.05, 52.99, 52.25, 51.28, 43.2642.94, 41.43, 37.49, 34.70, 31.89, 24.52, 24.21 , 23.76, 23.46, 22.15, 21.54, 18.76 ppm.
  • 35
  • [ 868540-16-3 ]
  • C9H17NO2*C3HF5O2 [ No CAS ]
  • carfilzomib [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; diethylamine; In N,N-dimethyl-formamide; at -5℃; for 1.5h; 4.5 g of compound 1 was dissolved in 126 ml DMF, together with 5.9 g HBTU, 2.1 g HOBt and 5.93 g compound of formula 6. The mixture was cooled to -5C and 2.7 ml of diethylamine were added dropwise. The mixture was stirred at -5C for 1.5 hour. To the mixture 90 ml of saturated aqueous NaHC03 solution were added. To the mixture 500 ml of ethyl acetate were added, the layers were separated. The organic layer was twice extracted with 135 ml of saturated aqueous solution of NaHC03 and with 90 ml of brine. The organic layer was dried over MgS04. The organic layer was concentrated to provide Carfilzomib in 86% of the theoretical yield.
  • 36
  • [ 868540-16-3 ]
  • C9H17NO2*C4HF7O2 [ No CAS ]
  • carfilzomib [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; diethylamine; In N,N-dimethyl-formamide; at -5℃; for 1.5h; 4.5 g of compound 2 was dissolved in 126 ml DMF, together with 5.1 g HBTU, 1.8 g HOBt and 5.2 g compound of formula 6. The mixture was cooled to -5C and 2.4 ml of diethylamine were added dropwise. The mixture was stirred at -5C for 1.5 hour. To the mixture 90 ml of saturated aqueous NaHC03 solution were added. To the mixture 500 ml of ethyl acetate were added, the layers were separated. The organic layer was twice extracted with 135 ml of saturated aqueous solution of NaHC03 and with 90 ml of brine. The organic layer was dried over MgS04. The organic layer was concentrated to provide Carfilzomib in 88% yield.
  • 37
  • [ 70637-28-4 ]
  • [ 868540-16-3 ]
  • 38
  • [ 868540-15-2 ]
  • [ 868540-16-3 ]
  • 39
  • [ 868540-16-3 ]
  • C25H35NO3Si*C2HF3O2 [ No CAS ]
  • (S)-N-((S)-1-((S)-1-((S)-2-((tert-butyldiphenylsilyloxy)methyl)oxiran-2-yl)-4-methyl-1-oxopentan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide [ No CAS ]
  • 40
  • [ 875309-83-4 ]
  • [ 868540-16-3 ]
  • 41
  • [ 868540-16-3 ]
  • (S)-N-((S)-1-((S)-1-((R)-2-(hydroxymethyl)oxiran-2-yl)-4-methyl-1-oxopentan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide [ No CAS ]
  • 42
  • [ 868540-16-3 ]
  • (S)-N-((S)-1-((S)-1-((S)-2-((methoxymethoxy)methyl)oxiran-2-yl)-4-methyl-1-oxopentan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide [ No CAS ]
  • 43
  • [ 868540-16-3 ]
  • (S)-N-((S)-1-((S)-1-((S)-2-(((2-methoxyethoxy)methoxy)methyl)-oxiran-2-yl)-4-methyl-1-oxopentan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide [ No CAS ]
  • 44
  • [ 868540-16-3 ]
  • ((S)-2-((4S,7S,10S,13S)-10-benzyl-7-isobutyl-15-methyl-1-morpholino-2,5,8,11-tetraoxo-4-phenethyl-3,6,9,12-tetraazahexadecanecarbonyl)oxiran-2-yl)methylmethanesulfonate [ No CAS ]
  • 45
  • [ 868540-16-3 ]
  • C2HF3O2*C10H19NO3 [ No CAS ]
  • (S)-N-((S)-1-((S)-1-((S)-2-(methoxymethyl)oxiran-2-yl)-4-methyl-1-oxopentan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide [ No CAS ]
  • 46
  • Leu-Phe-OMe trifluoroacetate [ No CAS ]
  • [ 868540-16-3 ]
  • 47
  • [ 868539-99-5 ]
  • [ 868540-16-3 ]
  • 48
  • [ 868540-16-3 ]
  • C7H13NO2*C2HF3O2 [ No CAS ]
  • (S)-4-methyl-N-((S)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxobutan-2-yl) amino)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)-4-phenyl butanamido)pentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% General procedure: To a cooled solution of 8q (0.7 g, 1.0 mmol) dissolved in anhydrousCH2Cl2 (50 mL) was added HOBt (0.2 g, 1.5 mmol). After 20 min, thetemperature of the reaction system was cooled to -15 C and EDC·HCl (0.3 g, 1.5 mmol) was added. Finally, a solution of 16c (0.3 g,1.0 mmol) and DIPEA (0.5 mL, 3.0 mmol) in anhydrous CH2Cl2 (5 mL)was added. The mixture was stirred at -15 C for 30 min and at roomtemperature for 12 h, finally quenched with water. The organic phasewas washed with 10% of citric acid, 5% of NaHCO3 and saturated brine,respectively, and dried over anhydrous Na2SO4, filtered and evaporatedto provide crude product. Column chromatography using dichloromethane/methanol (50:1) afforded 0.3 g of pure 36. Yield 65%.
  • 49
  • [ 868540-16-3 ]
  • C9H17NO2*C2HF3O2 [ No CAS ]
  • (S)-4-methyl-N-((S)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxohexan-2-yl) amino)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)-4-phenyl butanamido)pentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% General procedure: To a cooled solution of 8q (0.7 g, 1.0 mmol) dissolved in anhydrousCH2Cl2 (50 mL) was added HOBt (0.2 g, 1.5 mmol). After 20 min, thetemperature of the reaction system was cooled to -15 C and EDC·HCl (0.3 g, 1.5 mmol) was added. Finally, a solution of 16c (0.3 g,1.0 mmol) and DIPEA (0.5 mL, 3.0 mmol) in anhydrous CH2Cl2 (5 mL)was added. The mixture was stirred at -15 C for 30 min and at roomtemperature for 12 h, finally quenched with water. The organic phasewas washed with 10% of citric acid, 5% of NaHCO3 and saturated brine,respectively, and dried over anhydrous Na2SO4, filtered and evaporatedto provide crude product. Column chromatography using dichloromethane/methanol (50:1) afforded 0.3 g of pure 36. Yield 65%.
  • 50
  • [ 868540-16-3 ]
  • [ 1148157-29-2 ]
  • (S)-4-methyl-N-((S)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)-4-phenyl butanamido)pentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% General procedure: To a cooled solution of 8q (0.7 g, 1.0 mmol) dissolved in anhydrousCH2Cl2 (50 mL) was added HOBt (0.2 g, 1.5 mmol). After 20 min, thetemperature of the reaction system was cooled to -15 C and EDC·HCl (0.3 g, 1.5 mmol) was added. Finally, a solution of 16c (0.3 g,1.0 mmol) and DIPEA (0.5 mL, 3.0 mmol) in anhydrous CH2Cl2 (5 mL)was added. The mixture was stirred at -15 C for 30 min and at roomtemperature for 12 h, finally quenched with water. The organic phasewas washed with 10% of citric acid, 5% of NaHCO3 and saturated brine,respectively, and dried over anhydrous Na2SO4, filtered and evaporatedto provide crude product. Column chromatography using dichloromethane/methanol (50:1) afforded 0.3 g of pure 36. Yield 65%.
  • 51
  • [ 868540-16-3 ]
  • C13H17NO2*C2HF3O2 [ No CAS ]
  • (S)-4-methyl-N-((S)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-4-phenylbutan-2 -yl)amino)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% General procedure: To a cooled solution of 8q (0.7 g, 1.0 mmol) dissolved in anhydrousCH2Cl2 (50 mL) was added HOBt (0.2 g, 1.5 mmol). After 20 min, thetemperature of the reaction system was cooled to -15 C and EDC·HCl (0.3 g, 1.5 mmol) was added. Finally, a solution of 16c (0.3 g,1.0 mmol) and DIPEA (0.5 mL, 3.0 mmol) in anhydrous CH2Cl2 (5 mL)was added. The mixture was stirred at -15 C for 30 min and at roomtemperature for 12 h, finally quenched with water. The organic phasewas washed with 10% of citric acid, 5% of NaHCO3 and saturated brine,respectively, and dried over anhydrous Na2SO4, filtered and evaporatedto provide crude product. Column chromatography using dichloromethane/methanol (50:1) afforded 0.3 g of pure 36. Yield 65%.
  • 52
  • [ 13734-34-4 ]
  • [ 868540-16-3 ]
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