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[ CAS No. 830346-48-0 ] {[proInfo.proName]}

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Chemical Structure| 830346-48-0
Chemical Structure| 830346-48-0
Structure of 830346-48-0 * Storage: {[proInfo.prStorage]}
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Product Details of [ 830346-48-0 ]

CAS No. :830346-48-0 MDL No. :MFCD12546646
Formula : C13H9BrF4N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :RDQPTRWUBKZZFJ-UHFFFAOYSA-N
M.W : 381.12 Pubchem ID :11682386
Synonyms :

Calculated chemistry of [ 830346-48-0 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 22
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.23
Num. rotatable bonds : 3
Num. H-bond acceptors : 6.0
Num. H-bond donors : 1.0
Molar Refractivity : 74.7
TPSA : 54.86 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.52 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.25
Log Po/w (XLOGP3) : 2.96
Log Po/w (WLOGP) : 4.39
Log Po/w (MLOGP) : 3.19
Log Po/w (SILICOS-IT) : 4.64
Consensus Log Po/w : 3.49

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.27
Solubility : 0.0203 mg/ml ; 0.0000533 mol/l
Class : Moderately soluble
Log S (Ali) : -3.77
Solubility : 0.064 mg/ml ; 0.000168 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.91
Solubility : 0.000473 mg/ml ; 0.00000124 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.43

Safety of [ 830346-48-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 830346-48-0 ]

* 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 [ 830346-48-0 ]

[ 830346-48-0 ] Synthesis Path-Downstream   1~97

  • 1
  • [ 830346-48-0 ]
  • (R)-N-(tert-butoxycarbonyl)phenylglycinol [ No CAS ]
  • [ 830346-49-1 ]
YieldReaction ConditionsOperation in experiment
99% With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; for 14h; Add <strong>[830346-48-0]5-bromo-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione</strong> (2.2g, 5.8mmol at 25) )withTetrahydrofuran (35mL) was added to a 100mL single-necked round bottom flask, and (R)-tert-butyl (2-hydroxy-1-phenylethyl) carbamate (1.7g, 7.2mmol) andTriphenylphosphine (2.3g, 8.7mmol), then add diethyl azodicarboxylate (2.0g, 8.5mmol), continue to stir and react for 14 hours;The reaction was stopped, the product was spin-dried under reduced pressure, and separated and purified by column chromatography (petroleum ether/ethyl acetate (v/v)=3/1) to obtain the title compound as a white solid (3.42 g, 99%).
70% With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In toluene; at 5 - 20℃; To a stirred solution of 5-bromo-l-[2-fluoro-6-(trifluoromethyl)benzyl]-6- methylpyrimidine-2,4(lH,3H)-dione of Formula V (25 g) in toluene (275 ml) were added N- t-Boc-D-phenylglycinol of Formula VI (R3=OH, PG=Boc) (19.5 g) and triphenylphosphine (25.6 g) followed by slow addition of di tert-butyl azodicarboxylate in toluene solution (22.5 g in 100 ml) at 5-10C and stirred at RT for overnight. The resulting mixture was concentrated under vacuum to get 5-bromo-l-[2-fluoro-6-(trifluoromethyl) benzyl]-6- methyl-3-[2(R)-tert-butoxycarbonylamino-2-phenylethyl]-pyrimidine-2,4-(lH,3H)-dione which was crystallised in methanol: water (175 ml: 50 ml) to get pure compound of Formula II (27.5g, 70% yield).
With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; To 5-BROMO-1-[2-FLUORO-6-(TRIFLUOROMETHYL) benzyl] -6-methylpyrimidine- 2,4 (1FI, 3H)-DIONE LD (15 g, 39.4 mmol) in 225 mL of THF were added N-T-BOC-D- phenylglycinol (11.7 g, 49.2 mmol) and triphenylphosphine (15.5 g, 59.1 mmol), followed by addition of di-tert-butyl azodicarboxylate (13.6 g, 59.1 mmol). The resulting yellow solution was stirred overnight. The volatiles were evaporated and the residue was purified by silica gel with 3: 7 EtOAc/Hexane to give le as a white solid (23.6 g, 39.4 mmol). MS (CI) m/z 500.0 (MH+-Boc).
With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; To 5-BROMO-1- [2-FLUORO-6- (TRIFLUOROMETHYL) BENZYL]-6-METHYLPYRIMIDINE- 2,4 (1H, 3H)-DIONE LD (15 g, 39.4 mmol) in 225 mL of THF were added N-T-BOC-D- phenylglycinol (11.7 g, 49.2 mmol) and triphenylphosphine (15.5 g, 59.1 mmol), followed by addition of di-tert-butyl azodicarboxylate (13.6 g, 59.1 mmol). The resulting yellow solution was stirred overnight. The volatiles were evaporated and the residue was purified by silica gel with 3: 7 EtOAc/Hexane to give le as a white solid (23.6 g, 39.4 mmol). MS (CI) M/Z 500.0 (MH+-Boc).
With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 5 - 25℃; for 2.2h; 29.95 g of intermediate N-6, 26.86 g of D-BOC-phenylglycinol, 30.92 g of triphenylphosphine and 299 mL of tetrahydrofuran are loaded in that order into a round- bottom flask. It is cooled to 5 C and a solution of di-tert-butyl azodicarboxylate (27.19 g) dissolved in 150 mL of tetrahydrofuran is dripped in about 40 minutes. The system is brought to 25 C and kept in agitation for 1.5 hours. (0088) At the end of the reaction (HPLC control) the solvent is removed by distillation at reduced pressure at 45 C. The residue is added with 377 mL of isopropyl acetate and kept in agitation at 5-10 C for 1 hour. The suspension is filtered by washing the solid with 20 mL of isopropyl acetate. (0089) The liquid phase obtained by filtration is concentrated at reduced pressure at 45 C until a yellow oil is obtained that is reacted as such in the subsequent reaction. (0090) The compound N-6, used as a starting reactant of the method, has the appearance of a white solid; its purity, determined with HPLC, is 99%. 1H-NMK (400MHz, DMSO-d6): 511.91 (s, 1H); 7.66 (d, 1H, J = 7.6 Hz); 7.59-7.51 (m, 2H); 5.34 (s, 2H); 2.46 (s, 3H); (0091) A sample of the intermediate N-5 obtained in the test of the example, purified exclusively for analytical purposes, is analysed and identified through 1H-NMR and mass spectroscopy. 1H-NMK (400MHZ, DMSO-d6): 7.66 (d, 1H, J = 7.6 Hz); 7.61-7.48 (m, 2H); 7.36-7,21 (m, 5H); 5.35 (dd, 2H, J = 22,0/17.0 Hz); 4.93-4.88 (m, 1H); 4.10-3.99 (m, 2H); 2.53 (s, 3H); 1.35 (s, 9H).

  • 2
  • [ 830346-48-0 ]
  • [ 152547-72-3 ]
  • [ 832711-54-3 ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; To Boc-N-methyl-D-phenyglycinol 8a (8.9 g, 35 mmol) and 5-BROM-1- [2-fluoro-6- (trifluoromethyl) benzyl] -6-methylpyrimidine-2, 4 (1H, 3H)-dione 1d (12 g, 31.5 mmol) in dry THF, was added triphenylphosphine (12 g, 45. 6 mmol), then di-tert butyl diazocarboxylate (10.5 g, 45.6 mmol). The mixture was stirred at room temperature overnight. The mix was concentrated and purified by column chromatography to yield 21 g of white foam 8b. NMR indicated it contained 50% of a byproduct (T-BU02CNHNHC02-TBU). MS (M-Boc+H) + : 512.2, 514.2. NMR (CDC13), No., 7.55 (d, J = 7.8Hz, 1H), 7.45-7. 20 (m, 7H), 5.90-5. 18 (m, 3H), 4.95-4. 80 (m, 1H), 4.28 (dd, J = 17.1 & 5.4 Hz, 1H), 2.56 (s, 1. 5H), 2.50 (s, 3H), 2.41 (s, 1. 5H), 1.42 (s, 9H).
  • 3
  • [ 832711-65-6 ]
  • [ 830346-48-0 ]
  • [ 832711-58-7 ]
YieldReaction ConditionsOperation in experiment
100% With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 16h; A solution of 5-BROMO-L- (2-FLUORO-6-TRIFLUOROMETHYLBENZYL)-6- methyluracil LD (2.29 g, 6.0 mmol) in THF (20 mL) was treated with N (benzyloxycarbonyl)-R-1-hydroxylmethyl-1,2,3,4-tetrahydro-isoquinoline (1.96 g, 6.6 mmol, prepared from (R)-1, 2,3, 4-TETRAHYDRO-1-ISOQUINOLINE carboxylic acid via the borane reduction of Step 2A) and triphenylphosphine (2.36 g, 9.0 mmol) at room temperature, then di-tert-butylazodicarboxylate (2.07 g, 9.0 mmol) was introduced in several portions over 5 min. The mixture was stirred at room temperature for 16 hr, concentrated and purified by column chromatography on silica gel eluting with ethyl acetate/hexanes 2/3 to afford compound 9a (3.96 g, 100%), MS (CI) m/z 660.2, 662.2 (MH+).
  • 4
  • [ 830346-47-9 ]
  • [ 830346-48-0 ]
YieldReaction ConditionsOperation in experiment
87% With bromine; acetic acid; at 20℃; for 3h; Bromine (3.2 g) was added to a solution of 1-(2-fluoro-6-(trifluoromethyl)benzyl)- 6-methylpyrimidine-2,4(1H,3H)-dione (6.0 g, 0.019 mmol) in acetic acid and stirred for 3 h at ambient temperature. Residue obtained was filtered and filtrate was diluted with ethyl acetate. The ethyl acetate layer was washed with sat. NaHCO3 solution. Organic layer was separated, washed with Na2S2O3 solution and then concentrated to give titled solid material (6.6 g, 87 percent).
With bromine; acetic acid; for 2h; Bromine (16.5 mL, 0.32 mmol) was added to 1- [2-FLUORO-6- (trifluoromethyl) benzyl] -6-methylpyrimidine-2, 4 (1H, 3H)-DIONE lc (48. 5 g, 0.16 mol) in 145 mL of acetic acid. The resulting mixture became clear then formed precipitate within an hour. After 2 hours stirring, the yellow solid was filtered and washed with cold EtOAc to an almost white solid. The filtrate was washed with sat. NAHC03 and dried over NA2S04. Evaporation gave a yellow solid which was washed with ETOAC to give a light yellow solid. The two solids were combined to give 59.4 g of ld (0.156 mol) total NMR (CDC13) 8 2.422 (s, 3H), 5.478 (s, 2H), 7.246-7. 582 (m, 3H), 8.611 (s, 1H) ; MS (CI) M/Z 380.9 (MH+). 5-Bromo-1-[2, 6-difluorobenzyl]-6-methylpyrimidine-2, 4 (1H, 3H)-dione ld. 1 was made using the same procedure.
With bromine; acetic acid; for 2h; Bromine (16.5 mL, 0.32 mmol) was added to 1- [2-FLUORO-6- (trifluoromethyl) benzyl]-6-methylpyrimidine-2, 4 (1H, 3H)-dione lc (48.5 g, 0.16 mol) in 145 mL of acetic acid. The resulting mixture became clear then formed precipitate within an hour. After 2 hours stirring, the yellow solid was filtered and washed with cold EtOAc to an almost white solid. The filtrate was washed with sat. NAHC03 and dried over NA2S04. Evaporation gave a yellow solid which was washed with ETOAC to give a light yellow solid. The two solids were combined to give 59.4 g of LD (0.156 mol) total NMR (CDC13) 8 2.4 (s, 3H), 5.48 (s, 2H), 7.25-7. 58 (M, 3H), 8.61 (s, 1H) ; MS (CI) m/z 380.9 (MH).
With bromine; acetic acid; for 2h; Bromine (16.5 mL, 0.32 mmol) was added to 1-[2-FLUORO-6- (trifluoromethyl) benzyl]-6-methylpyrimidine-2, 4 (1H, 3H)-DIONE 4c (48. 5 g, 0.16 mol) in 145 mL of acetic acid. The resulting mixture became clear then formed precipitate within an hour. After 2 hours stirring, the yellow solid was filtered and washed with cold EtOAc to an almost white solid. The filtrate was washed with sat. NAHC03 and dried over NA2S04. Evaporation gave a yellow solid which was washed with ETOAC to give a light yellow solid. The two solids were combined to give 59.4 g OF 4D (0.156 mol) total NMR (CDCL3) 8 2.422 (s, 3H), 5.478 (s, 2H), 7.246-7. 582 (M, 3H), 8.611 (s, 1H) ; MS (CI) M/Z 380.9 (MH+).
With bromine; acetic acid; for 2h; Step 1D: Preparation of 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6- methylpyrimidine-2,4 (1H,3H)-dione 1-1; Bromine (16.5 mL, 0.32 mmol) was added to 1-[2-fluoro-6- (trifluoromethyl)benzyl]-6-methylpyrimidine-2,4(IH,3H)-dione 1c (48.5 g, 0.16 mol) in 145 mL of acetic acid. The resulting mixture became clear then formed precipitate within an hour. After 2 hours stirring, the yellow solid was filtered and washed with cold EtOAc to an almost white solid. The filtrate was washed with sat. NaHC03 and dried over Na2S04. Evaporation gave a yellow solid which was washed with EtOAC to give a light yellow solid. The two solids were combined to give 59.4 g of 1-1 (0.156 mol) total. 1H NMR (CDC13) No. 2.4 (3H, s), 5.48 (2H, s), 7.25 - 7.58 (3H, m), 8.61 (1H, s) ; MS (CI) m/z 380.9 (MH+).

  • 5
  • [ 830346-48-0 ]
  • [ 869984-24-7 ]
  • [ 869984-25-8 ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; Step 3C:; To the Boc-amino alcohol 3b (847 mg, 3.15 mmol) and 5-bromo-l-[2- fluoro-6-(trifluoromethyl)benzyl]-6-methylpyrimidine-2,4(1H,3H)-dione 1-1 (800 mg, 2.1 mmol) in dry THF (15 mL) were added diisopropyl azodicarboxylate (DIAD, 0.62 mL, 15 mmol) and triphenylphosphine (826 mg, 3.15 mmol). The mixture was stirred overnight, concentrated and purified by silica gel chromatography (EtOAc/Hexane) to yield 3c (1.78 g, which contains some DIAD related side product). MS (CI) m/z 530.2/532.2 (MH+), HPLC: tR = 2.7 min (Method 2).
  • 6
  • [ 830346-48-0 ]
  • [ 869984-29-2 ]
  • [ 869984-30-5 ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 3h; Step 4B:; To oil 4a in dry THF (15 mL) was added the 5-bromo-l-[2-fluoro-6- (trifluoromethyl)benzyl]-6-methylpyrimidine-2,4(IH,3H)-dione 1-1 (1.18 g, 3.1 mmol), followed by addition of triphenylphosphine (1.22 g, 4.65 mmol) and diisopropyl azodicarboxylate (0.92 mL, 4.65 mmol). The mixture was stirred at room temperature for 3 hours, then was concentrated and dissolved in ethyl acetate (100 mL). The ethyl acetate layer was washed with water and brine, dried over MgS04 and concentrated. Purification by silica gel chromatography (hexane/EtOAc 3/2 as elutant) gave 1.26 g of 4b. MS (CI) m/z 544.1/546.1 (MH+), HPLC: tR = 3.11 min (Method 2).
  • 7
  • [ 830346-48-0 ]
  • [ 79069-15-1 ]
  • [ 1044526-13-7 ]
  • 8
  • [ 830346-48-0 ]
  • (R)-2-tertbutoxycarbonylamino-1-propanol [ No CAS ]
  • [ 1044526-16-0 ]
  • 9
  • [ 830346-48-0 ]
  • [ 79069-13-9 ]
  • [ 1044526-09-1 ]
  • 10
  • [ 830346-48-0 ]
  • [ 150736-72-4 ]
  • [ 1044526-11-5 ]
  • 11
  • [ 830346-48-0 ]
  • [ 150736-71-3 ]
  • [ 1044526-18-2 ]
  • 13
  • [ 2759-28-6 ]
  • [ 830346-48-0 ]
  • [ 1308380-31-5 ]
YieldReaction ConditionsOperation in experiment
79% In acetonitrile; at 120℃; for 1.5h;microwave irradiation; 5-bromo-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione(1.50g, 3.94mmol), 1-benzyl-piperazine(5.5mL, 31.5mmol), and acetonitrile(1mL) were placed in a microwave vessel and heated at 120C for 1.5 hr by microwave irradiation with stirring. Following concentration, the residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate/dichloromethane, 1/2/1) and dried in a vacuum to afford the 1.48 g of the compound as a white solid (yield 79%). 1H NMR (300MHz, CDCl3) δ 2.15(2H, m), 2.31(3H, s), 2.50 (2H, m), 2.78 (2H, m), 3.52 (3H, s), 3.58 (2H, m), 5.36(2H, s), 7.19-7.41 (7H, m), 7.53 (1H, d)
79% In acetonitrile; at 120℃; for 1.5h;Microwave irradiation; Step A. 5-(4-benzyl-piperazin-1-yl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione 5-bromo-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione (1.50 g, 3.94 mmol), 1-benzyl-piperazine (5.5 mL, 31.5 mmol), and acetonitrile (1 mL) were placed in a microwave vessel and heated at 120 C. for 1.5 hr by microwave irradiation with stirring. Following concentration, the residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate/dichloromethane, 1/2/1) and dried in a vacuum to afford the 1.48 g of the compound as a white solid (yield 79%). 1H NMR (300 MHz, CDCl3) δ 2.15 (2H, m), 2.31 (3H, s), 2.50 (2H, m), 2.78 (2H, m), 3.52 (3H, s), 3.58 (2H, m), 5.36 (2H, s), 7.19-7.41 (7H, m), 7.53 (1H, d)
79% In acetonitrile; at 120℃;Microwave irradiation; The mixture of compound7 (1.50 g, 3.94 mmol) and 1-benzylpiperazine (5.5 mL,31.5 mmol) in acetonitrile (1 mL) was reacted under. microwaveirradiation at 120 C for 1.5 h. The mixture was concentrated, followedby purification using silica gel chromatography (hexane/EtOAc/CH2Cl2, 1:2:1) to afford 4-benzyl piperazine adduct as awhite solid (1.48 g, 79%). 1H NMR (300 MHz, CDCl3) δ 2.15 (m, 2H),2.31 (s, 3H), 2.50 (m, 2H), 2.78 (m, 2H), 3.52 (s, 3H), 3.58 (m, 2H),5.36 (s, 2H), 7.19-7.41 (m, 7H), 7.53 (m, 1H). A solution of the abovecompound (1.48 g, 3.11 mmol) dissolved in CH2Cl2/MeOH (1:1,10 mL) was hydrogenated over 10% Pd/C (280 mg) under atmosphericpressure at room temperature for 5 h. The mixture wasfiltered through celite, followed by concentration of the filtratesolution. The residue was purified using column chromatographyusing amine silica gel (CH2Cl2/MeOH, 10:1) to yield compound 8 aswhite solid (934 mg, 78%). mp 78 C, 1H NMR (300 MHz, CDCl3)δ 7.54 (d, J 7.8 Hz, 1H), 7.41 (m, 1H), 7.24 (m, 1H), 5.38 (s, 2H), 3.43(m, 2H), 2.96 (m, 2H), 2.81 (m, 2H), 2.52 (m, 2H), 2.33 (s, 3H).
  • 17
  • [ 830346-48-0 ]
  • [ 1308379-59-0 ]
  • 18
  • [ 830346-48-0 ]
  • (R)-tert-butyl (2-(3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-5-(4-(3-nitrobenzyl)piperazin-1-yl)-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)-1-(2-hydroxyphenyl)ethyl)carbamate [ No CAS ]
  • 19
  • [ 830346-48-0 ]
  • [ 1308379-69-2 ]
  • 20
  • [ 830346-48-0 ]
  • [ 1308379-70-5 ]
  • 21
  • [ 830346-48-0 ]
  • C43H50F4N6O9 [ No CAS ]
  • 22
  • [ 830346-48-0 ]
  • C45H54F4N6O9 [ No CAS ]
  • 23
  • [ 830346-48-0 ]
  • [ 1308378-34-8 ]
  • 24
  • [ 830346-48-0 ]
  • C37H40F4N6O6 [ No CAS ]
  • 25
  • [ 830346-48-0 ]
  • C38H42F4N6O6 [ No CAS ]
  • 26
  • [ 830346-48-0 ]
  • C37H39F5N6O6 [ No CAS ]
  • 27
  • [ 830346-48-0 ]
  • C38H42F4N6O6 [ No CAS ]
  • 28
  • [ 830346-48-0 ]
  • C37H39F5N6O6 [ No CAS ]
  • 29
  • [ 830346-48-0 ]
  • C37H39F5N6O6 [ No CAS ]
  • 30
  • [ 830346-48-0 ]
  • C38H41F5N6O7 [ No CAS ]
  • 31
  • [ 830346-48-0 ]
  • C38H41F5N6O7 [ No CAS ]
  • 32
  • [ 830346-48-0 ]
  • C38H41F5N6O6 [ No CAS ]
  • 33
  • [ 830346-48-0 ]
  • C38H41F5N6O6 [ No CAS ]
  • 34
  • [ 830346-48-0 ]
  • [ 1308380-26-8 ]
  • 35
  • [ 830346-48-0 ]
  • C37H40F7N5O6 [ No CAS ]
  • 36
  • [ 830346-48-0 ]
  • C37H39F8N5O6 [ No CAS ]
  • 37
  • [ 830346-48-0 ]
  • C37H39F8N5O5 [ No CAS ]
  • 38
  • [ 830346-48-0 ]
  • C38H42F7N5O6 [ No CAS ]
  • 39
  • [ 830346-48-0 ]
  • C38H41F8N5O6 [ No CAS ]
  • 40
  • [ 830346-48-0 ]
  • C38H41F8N5O5 [ No CAS ]
  • 41
  • [ 830346-48-0 ]
  • C36H37F8N5O5*H3O4P [ No CAS ]
  • 42
  • [ 830346-48-0 ]
  • [ 1308376-54-6 ]
  • 43
  • [ 830346-48-0 ]
  • [ 1308378-38-2 ]
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  • [ 830346-48-0 ]
  • [ 1308378-41-7 ]
  • 45
  • [ 830346-48-0 ]
  • [ 1308378-42-8 ]
  • 46
  • [ 830346-48-0 ]
  • [ 1308378-44-0 ]
  • 47
  • [ 830346-48-0 ]
  • [ 1308378-45-1 ]
  • 48
  • [ 830346-48-0 ]
  • [ 1308376-92-2 ]
  • 49
  • [ 830346-48-0 ]
  • [ 1308375-84-9 ]
  • 50
  • [ 830346-48-0 ]
  • [ 1308376-93-3 ]
  • 51
  • [ 830346-48-0 ]
  • [ 1308375-83-8 ]
  • 52
  • [ 830346-48-0 ]
  • [ 1308376-62-6 ]
  • 53
  • [ 830346-48-0 ]
  • [ 1308378-48-4 ]
  • 54
  • [ 830346-48-0 ]
  • [ 1308378-49-5 ]
  • 55
  • [ 830346-48-0 ]
  • [ 1308378-51-9 ]
  • 56
  • [ 830346-48-0 ]
  • [ 1308379-02-3 ]
  • 57
  • [ 830346-48-0 ]
  • [ 1308378-99-5 ]
  • 58
  • [ 830346-48-0 ]
  • [ 1308378-96-2 ]
  • 59
  • [ 830346-48-0 ]
  • ethyl (R)-4-((tert-butoxycarbonyl)(2-hydroxy-1-phenylethyl)amino)butanoate [ No CAS ]
  • ethyl (R)-4-((2-(5-bromo-3-(2-fluoro-6-trifluoromethylbenzyl)-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-1-phenylethyl)(tert-butoxycarbonyl)amino)butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 16h;Inert atmosphere; Ethyl (R)-4-((tert-butoxycarbonyl)(2-hydroxy-l -phenyl ethyl) amino)butanoate (III; R is ethyl) (1.0 g), 5-bromo-l-(2-fluoro-6-trifluoromethyl)benzyl-6-methylpyrimidine-2,4 (1H, 3H)-dione (II) (1.08 g), Triphenyl phosphine (1.49 g) were added to THF (30 mL) at room temperature under nitrogen atmosphere. DIAD (1.11 mL) was added to the reaction mixture and stirred for 16 hours at room temperature. Water (60 volume) was added to the reaction mixture followed by ethylacetate (60 mL) was added then the layers were separated. The organic layer was dried over sodium sulfate and evaporated below 50C under reduced pressure to obtain the crude compound. The crude compound was purified by silica gel (60/120 mesh) withl5-20% EtOAc/Hexane to obtain the title compound. Yield (1.3 g). Purity: 68.87% (by HPLC); l NMR (DMSO-d6) δ 1.15-2.0 (11H), 2.43-2.48 (4H), 3.9 (2H), 4.71-4.8 (5H), 5.3 -5.4 (3H), 7.28-7.3 (8H), 8.4 (2H); m/z: 616 (M-BOC)+
  • 60
  • [ 830346-46-8 ]
  • [ 830346-48-0 ]
  • 61
  • [ 830346-48-0 ]
  • C28H25F4N3O3 [ No CAS ]
  • 62
  • [ 830346-48-0 ]
  • (2-{(S)-1-amino-3-[3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-5-phenyl-3,6-dihydro-2H-pyrimidin-1-yl]-propyl}-phenoxy)-acetic acid [ No CAS ]
  • 63
  • [ 830346-48-0 ]
  • 3-(2-{(S)-1-amino-3-[3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-5-phenyl-3,6-dihydro-2H-pyrimidin-1-yl]-propyl}-phenoxy)-propionic acid [ No CAS ]
  • 64
  • [ 830346-48-0 ]
  • 4-(2-{(S)-1-amino-3-[3-(2-fluoro-6-trifluoromethyl-benzyl)-5-(3-isopropyl-phenyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-propyl}-phenoxy)-butyric acid [ No CAS ]
  • 65
  • [ 830346-48-0 ]
  • C36H37F4N3O7 [ No CAS ]
  • 66
  • [ 830346-48-0 ]
  • 5-(2-{1-amino-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-ethyl}-phenoxy)-pentanoic acid [ No CAS ]
  • 67
  • [ 830346-48-0 ]
  • C38H40F5N3O8 [ No CAS ]
  • 68
  • [ 830346-48-0 ]
  • 3-(2-{(S)-1-amino-3-[3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-5-phenyl-3,6-dihydro-2H-pyrimidin-1-yl]-propyl}-phenoxy)-propionic acid sodium salt [ No CAS ]
  • 69
  • [ 830346-48-0 ]
  • C21H18BrF4N3O3 [ No CAS ]
  • 70
  • [ 830346-48-0 ]
  • C22H20BrF4N3O3 [ No CAS ]
  • 71
  • [ 830346-48-0 ]
  • [ 869984-51-0 ]
  • 72
  • [ 830346-48-0 ]
  • [ 869984-34-9 ]
  • 73
  • [ 830346-48-0 ]
  • [ 869984-48-5 ]
  • 74
  • [ 830346-48-0 ]
  • [ 869984-31-6 ]
  • 75
  • [ 830346-48-0 ]
  • [ 869984-32-7 ]
  • 76
  • [ 830346-48-0 ]
  • C35H37F4N3O6 [ No CAS ]
  • 77
  • [ 830346-48-0 ]
  • [ 869984-35-0 ]
  • 78
  • [ 830346-48-0 ]
  • C35H35F4N3O7 [ No CAS ]
  • 79
  • [ 830346-48-0 ]
  • C33H38BrF4N3O7 [ No CAS ]
  • 80
  • [ 830346-48-0 ]
  • [ 869984-33-8 ]
  • 81
  • [ 830346-48-0 ]
  • C40H45F4N3O7 [ No CAS ]
  • 82
  • [ 830346-48-0 ]
  • [ 869984-36-1 ]
  • 83
  • [ 830346-48-0 ]
  • C40H44F5N3O8 [ No CAS ]
  • 84
  • [ 133116-83-3 ]
  • [ 830346-48-0 ]
  • 85
  • [ 239087-06-0 ]
  • [ 830346-48-0 ]
  • 86
  • [ 15018-56-1 ]
  • [ 239087-08-2 ]
  • [ 830346-48-0 ]
YieldReaction ConditionsOperation in experiment
81% With potassium carbonate; In N,N-dimethyl-formamide; at 75 - 85℃; Add to the three-necked flask5-bromo-6-methylpyrimidine-2,4(1H,3H)-dione 1 (20.50 g, 100 mmol)And <strong>[239087-08-2]2-(bromomethyl)-1-fluoro-3-trifluoromethylbenzene</strong> 2 (25.70 g, 100 mmol)And N,N-dimethylformamide (103 mL),After stirring and stirring, potassium carbonate (27.64 g, 200 mmol) was added.After stirring uniformly, the mixture was heated to 75 to 85 C to react overnight. Water (205 mL) was added to the end of the reaction to precipitate a large amount of solid, which was filtered and dried to give Compound 3 (30.88 g, 81%).
  • 87
  • [ 830346-48-0 ]
  • (R)-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-3-[2-(2-oxopyrrolidin-1-yl)-2-phenylethyl]-1,2,3,4-tetrahydropyrimidine-2,4-dione [ No CAS ]
  • 88
  • [ 830346-48-0 ]
  • [ 834153-87-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: iron(III)-acetylacetonate; N,N,N,N,-tetramethylethylenediamine / tetrahydrofuran / 0 - 45 °C 2: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 90 - 100 °C 3: sodium hydroxide; water / ethanol / 55 - 60 °C
  • 89
  • [ 830346-48-0 ]
  • C7H6BrFMgO [ No CAS ]
  • [ 1150560-59-0 ]
YieldReaction ConditionsOperation in experiment
77% With iron(III)-acetylacetonate; N,N,N,N,-tetramethylethylenediamine; In tetrahydrofuran; at 0 - 45℃; Compound 3 (38.11 g, 100 mmol) and tetrahydrofuran (190 mL) were added to a three-necked flask, stirred and dissolved, and then cooled to 0 to 5 C in an ice salt bath, and iron triacetylacetonate (1.77 g, 5 mmol), tetramethylethylenediamine was added. (2.32 g, 20 mmol), nitrogen was switched under vacuum three times, and a solution of Grignard reagent 4 (200 mmol, 190 mL) in tetrahydrofuran was added dropwise, and the mixture was heated to 40 to 45 C for 6 to 8 hours. After completion of the reaction, dilute hydrochloric acid (2 mol/L, 381 mL) was added to quench the reaction, and solid solids were separated and filtered to give compound 5 (32.83 g, 77%).
  • 90
  • [ 830346-48-0 ]
  • [ 352303-67-4 ]
  • [ 1150560-59-0 ]
YieldReaction ConditionsOperation in experiment
76% KOH solution (10 mL) (6.03 g, 0.107 mol) was added to a solution of (2-fluoro-3- methoxyphenyl)boronic acid (10.0 g, 0.026 mol) and 5-bromo-1-(2-fluoro-6- (trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione (5.35 g, 0.031 mol) in acetone (30 mL) and water (20 mL). Reaction mixture was degassed for 30 min, then tri- t-butylphosphonium tetrafluoroborate (80 mg) and Pd(OAc)2 (30 mg) was added. Reaction mixture was stirred at 70C for 10 h and further cooled to ambient temperature. Acetic acid (4.5 mL) was added to give colorless material, which was filtered, washed with methanol and dried to give 5-(2-fluoro-3-methoxyphenyl)-1-(2-fluoro-6- (trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione (8.49 g, 76 %).1H NMR (400 MHz, DMSO-d6) delta 11.58 (s, 1H), 7.58 (m, 3H), 7.15 (m, 2H), 6.72 (m, 1H), 5.33 (s, 2H) 3.84 (s, 3H), 2.08 (s, 3H); MS: 427.3 [M+H]+.
  • 91
  • [ 830346-48-0 ]
  • benzyl (R)-(2-(5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-1-phenylethyl)carbamate [ No CAS ]
  • 95
  • [ 830346-48-0 ]
  • C13H9BrF4N2O2Zn [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid; zinc; In toluene; at 30 - 70℃; for 4h;Inert atmosphere; 1) In a 250mL three-necked flask, add 20mL of toluene at room temperature, 300 mesh zinc powder (2.6g, 39.36mmoL), and replace with nitrogen for three times. Add p-toluenesulfonic acid (0.23g, 1.31mmoL) dropwise, warm to 60-70 C, and keep warm. 0.5h, cool down to 10-20 . A solution of compound 2-1 (10.0 g, 26.24 mmoL) in toluene (20 mL) was added dropwise. After the dropwise addition, the mixture was kept at 30-40 C for 4 hours to obtain intermediate compound 2-2. The temperature was lowered to 10 ± 5 C until use.
  • 96
  • [ 830346-48-0 ]
  • C7H6FIOZn [ No CAS ]
  • [ 1150560-59-0 ]
YieldReaction ConditionsOperation in experiment
83% With tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine; In dimethyl sulfoxide; at 60 - 70℃; for 6h;Inert atmosphere; 2) Add 14mL of dimethyl sulfoxide at room temperature, add compound 1-2 (15.88g, 41.67mmoL), tris (dibenzylideneacetone) dipalladium (0.50g, 0.56mmoL), tris (o-methylphenyl) Phosphorus (0.34 g, 1.12 mmoL), replaced with nitrogen three times, and warmed to 60-70 C. The dimethyl sulfoxide solution of compound 2-1 in the three-necked flask was added dropwise. After the dropwise addition was completed, the temperature was maintained at 60-70 C for 6 hours.3) Add 100 mL of dichloromethane, filter the reaction solution through diatomaceous earth, combine the filtrates, concentrate under vacuum at 50 C until there are no obvious droplets, lower the temperature to 20-30 C, add 120 mL of water dropwise, precipitate a solid, and filter to obtain a off-white solid. Dry at 50-60 C. The crude product was heated to 60-65 C in ethanol for 0.6h, slowly cooled to 10-20 C for crystallization, and filtered to dryness to obtain 10.4 g of pure white compound 4 with a purity of 97.2% and a yield of 83%.
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