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[ CAS No. 1006-64-0 ] {[proInfo.proName]}

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Product Details of [ 1006-64-0 ]

CAS No. :1006-64-0 MDL No. :MFCD01631835
Formula : C10H13N Boiling Point : -
Linear Structure Formula :- InChI Key :JUTDHSGANMHVIC-UHFFFAOYSA-N
M.W : 147.22 Pubchem ID :261892
Synonyms :

Calculated chemistry of [ 1006-64-0 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.4
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 50.43
TPSA : 12.03 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) : -5.86 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.2
Log Po/w (XLOGP3) : 1.89
Log Po/w (WLOGP) : 1.41
Log Po/w (MLOGP) : 2.1
Log Po/w (SILICOS-IT) : 2.58
Consensus Log Po/w : 2.03

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.28
Solubility : 0.771 mg/ml ; 0.00524 mol/l
Class : Soluble
Log S (Ali) : -1.77
Solubility : 2.53 mg/ml ; 0.0172 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.31
Solubility : 0.0728 mg/ml ; 0.000494 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.38

Safety of [ 1006-64-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1006-64-0 ]

* 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 [ 1006-64-0 ]

[ 1006-64-0 ] Synthesis Path-Downstream   1~88

  • 1
  • [ 700-91-4 ]
  • [ 1006-64-0 ]
YieldReaction ConditionsOperation in experiment
82% EXAMPLE VI Asymmetric Reduction (in Hydrogen) of 2-phenyl-3,4-dihydro-5H-pyrrole to 2-phenyl-pyrrolidine The procedure of Example III was followed to reduce 2-phenyl-3,4-dihydro-5H-pyrrole (61 mg., 0.42 mmol). The reaction yielded 2-phenylpyrrolidine at 82% yield and 92-96% ee a determined by GLC of the Mosher Amides (prepared as described in Example I) using a Cyclodex B column.
With sodium tetrahydroborate; In methanol; water; at 20℃; A flask equipped with a frit with Schlenk valves and sealed with a two-necked dummy flask on the other end was charged with pyrrolidin-2-one (2.0g, 24mmol), diethyl ether (50mL) and triethylamine (3.5mL, 25mmol, 1.05 equiv). The mixture was cooled to 0C before chlorotrimethylsilane (3.2mL, 25mmol, 1.05 equiv) was added slowly. Once the addition was completed, the mixture was stirred under reflux for 30min, then cooled to room temperature and the resulting Et3NHCl filtered off under argon through the glass frit into the round-bottomed flask. To the filtrate was slowly added under argon a 3M solution of phenylmagnesium bromide in THF (8mL, 24mmol, 1.0 equiv) and the resulting mixture was stirred under reflux for further 3h. The mixture was allowed to cool to room temperature before it was quenched with 1M HCl aq. solution (10mL). The aqueous phase was separated, basified to pH 10 with 2M NaOH solution and extracted with EtOAc (3×20mL). The combined organic phase was washed with brine (10mL), then dried (Na2SO4), and concentrated in vacuo to give I as a colorless oil, which was used without further purification. To a solution of the crude I in MeOH/H2O (4:1, 25mL) was added NaBH4 (980mg, 26mmol, 1.1 equiv). The mixture was stirred at room temperature overnight before it was acidified to pH 1-3 with a 2M HCl aq. solution and maintained at this pH for 30min. Then, the mixture was basified to pH 13-14 with 2M NaOH solution and it was extracted with CH2Cl2 (3×30mL). The combined organic phase was dried (Na2SO4) and concentrated in vacuo to give II as a colorless oil, which was used without further purification. To a solution of the crude 2-phenylpirrolidine and pyridine (2.9mL, 36mmol, 1.5 equiv) in THF (50mL), cooled to 0C and under Ar, was added slowly 2-pyridylsulfonyl chloride (6.4g, 36mmol, 1.5 equiv).19 The resulting solution was allowed to reach room temperature and stirred at room temperature overnight. The mixture was quenched with a sat aq. NH4Cl solution (40mL) and extracted with EtOAc (3×50mL). The combined organic phase was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (cyclohexane-EtOAc 4:1) to afford N-(2-pyridylsulfonyl)-2-phenylpyrrolidine 1 as a white solid; yield: 1.44g (21%); mp: 101-103C. 1H NMR (300MHz, CDCl3) delta 8.69 (d, J=4.6Hz, 1H), 7.85-7.74 (m, 2H), 7.48-7.41 (m, 1H), 7.30-7.13 (m, 5H), 5.14 (dd, J=7.8, 3.3Hz, 1H), 3.83-3.64 (m, 2H), 2.31-2.15 (m, 1H), 2.00-1.74 (m, 3H). 13C NMR (75MHz, CDCl3) delta 149.9, 143.0, 137.6, 128.2, 126.9, 126.4, 126.3, 126.1, 122.9, 63.9, 50.0, 35.8, 24.2. ESI+ calcd. for C15H17N2O2S (M+H)+: 289.1005. Found: 289.1011.
  • 3
  • [ 6919-61-5 ]
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  • 4
  • [ 132959-49-0 ]
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  • 5
  • [ 882-33-7 ]
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  • 6
  • (S)-3-Methyl-2-((S)-2-phenyl-pyrrolidin-1-yl)-butyric acid methyl ester [ No CAS ]
  • [ 1006-64-0 ]
  • 8
  • [ 79-37-8 ]
  • [ 1006-64-0 ]
  • 1,2-Bis-((S)-5-phenyl-pyrrolidin-3-yl)-ethane-1,2-dione [ No CAS ]
  • 10
  • [ 1006-64-0 ]
  • [ 99-33-2 ]
  • 2-phenyl-N-(3,5-dinitrobenzoyl)-pyrrolidine [ No CAS ]
  • 11
  • [ 106-39-8 ]
  • [ 1006-64-0 ]
  • (S)-N-(4-chlorophenyl)-2-phenylpyrrolidine [ No CAS ]
  • 12
  • [ 92-66-0 ]
  • [ 1006-64-0 ]
  • 1-Biphenyl-4-yl-2-phenyl-pyrrolidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; platinum Hydrogenation;
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; platinum Hydrogenation;
  • 15
  • [ 1006-64-0 ]
  • [ 506-68-3 ]
  • [ 1068573-97-6 ]
  • 16
  • N-(3-chloropropyl)phenylmethanimine [ No CAS ]
  • [ 1006-64-0 ]
  • 18
  • (S)-ethyl 2-(2-phenylpyrrolidin-1-yl)-2-oxoacetate [ No CAS ]
  • [ 1006-64-0 ]
  • 19
  • [ 1006-64-0 ]
  • [ 4755-77-5 ]
  • [ 866994-05-0 ]
  • 20
  • [ 1006-64-0 ]
  • [ 50-00-0 ]
  • [ 938-36-3 ]
YieldReaction ConditionsOperation in experiment
72% With formic acid; In water; at 150℃; for 0.0833333h;Sealed tube; Microwave irradiation; Following a procedure reported by Turner,34 commercially available <strong>[1006-64-0]2-phenylpyrrolidine</strong> (3.4 mmol, 500 mg) was suspended in H2O (4mL) in a microwave test tube and formic acid (3.7 mmol, 141 muL) and formaldehyde (35% solution in H2O, 3.7 mmol, 320 muL) were added at r.t. The tube was sealed and was heated using microwave irradiation at 150 C for 5 min. The reaction mixture was allowed to cool to r.t., then it was basified to pH 14 using an aq solution of NaOH (2.0 M) and extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by Kugelrohr distillation to afford the pure tertiary amine (396 mg, 72%) as a colourless liquid. IR (neat): 2968, 2775, 1454, 1044, 754, 699 cm-1. 1H NMR (400 MHz, CDCl3): delta = 7.36-7.29 (m, 4 H, Ar-H), 7.23 (m, 1 H,Ar-H), 3.24 (td, J1 = 9.4 Hz, J2 = 1.8 Hz, 1 H, 4-H), 3.03 (t, J = 8.8 Hz, 1 H,1-H), 2.28 (m, 1 H, 4-H), 2.17 (m, 1 H, 2-H), 2.17 (s, 3 H, CH3), 1.95 (m,1 H, 3-H), 1.78 (m, 2 H, 2-H + 3-H). 13C NMR (101 MHz, CDCl3): delta = 143.40 (Ar-C), 128.47 (2 C, Ar-C),127.62 (2 C, Ar-C), 127.12 (Ar-C), 71.79 (1-C), 57.22 (4-C), 40.62(CH3), 35.29 (2-C), 22.63 (3-C). HRMS (ESI): m/z [M + H]+ calcd for C11H16N: 162.127726; found:162.127190.
41% The starting material was prepared as follows : 1-Methyl-<strong>[1006-64-0]2-phenyl-pyrrolidine</strong> A solution of <strong>[1006-64-0]2-phenylpyrrolidine</strong> (1. 00 g, 6. 79 mmol ; Array BIOPHARMA. INC.) and paraformaldehyde (0. 320 g, 10. 7 MMOL) in MEOH (15 ml) stirred at room temperature for 45 minutes. Sodium cyanoborohydride (0. 70 g, 11 MMOL) was added slowly, and the mixture then stirred for 12 hours. The solvent was removed under reduced pressure. A solution of the resultant residue in ethyl acetate was washed with sat. NAHC03, dried over MGS04, filtered, and concentrated. Purification via column chromatography (40% EtOAc/hexane) provided 0. 45 G of an oil in 41% yield, which displayed a'H NMR spectrum that matched previous spectra (Lewis, et al J. Am. Chem. Soc., 113, 3498-3506 (1991)) and was used without further purification. ESIMS (MH+) : 162
  • 21
  • [ 1006-64-0 ]
  • 1-{4-[2-oxo-2-(2-phenyl-1-pyrrolidinyl)ethyl]phenyl}-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% A solution of {4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1 /-/-indazol-1-yl]phenyl}acetic acid(65mg, 0.2mmol) in dichloromethane (2ml) was treated with 1 ,1 '-carbonyldiimidazole(32.5mg, 0.2mmol) in one portion at room temperature. Stirring was continued at room temperature for 15 minutes. Then <strong>[1006-64-0]2-phenylpyrrolidine</strong> (29mg, 0.2mmol) was added and stirring continued for 1 hour. Most of the solvent was removed under reduced pressure and the crude product was further purified by MDAP to give the title compound (55mg,61 %).LC/Mass Spec (ES): Found 454 (ES+), retention time 3.61 mins. C26H26F3N3O requires453.
  • 22
  • [ 1006-64-0 ]
  • (5-(4-chlorophenyl)isoxazol-4-yl)(2-phenylpyrrolidin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
General Procedure for compounds made in Table 1: To a solution of the carboxylic acid (0.5 mmol) in dry toluene (1.5 ml) at 0 C. was added oxalyl chloride (0.65 mmol) and DMF (2011). The reaction mixture was stirred at ambient temp. for 1.5 h, concentrated, and then dissolved in CH2Cl2. To this was added sym-collidine (1.5 mmol) and the amine were then added. The reaction mixture was stirred at ambient temp. for 18 h, and then diluted with CH2Cl2 and water. The aqueous layer was extracted with CH2Cl2 and the combined organic extracts were dried over Na2SO4, filtered, and concentrated. The crude product was purified by preparative HPLC to give the corresponding amide.
  • 23
  • [ 1006-64-0 ]
  • [ 76-05-1 ]
  • N-cyclopropyl-3-(2-(2-phenylpyrrolidin-1-yl)pyrrolo[1,2-f][1,2,4]triazin-4-ylamino)-1H-pyrazole-5-carboxamide TFA salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 102 N-Cyclopropyl-3-(2-(2-phenylpyrrolidin-1-yl)pyrrolo[1,2-f][1,2,4]triazin-4-ylamino)-1H-pyrazole-5-carboxamide A mixture of 3-(2-chloropyrrolo[1,2-f][1,2,4]triazin-4-ylamino)-N-cyclopropyl-1H-pyrazole-5-carboxamide (30 mg, 0.094 mmol) (Example 100C), <strong>[1006-64-0]2-phenylpyrrolidine</strong> (13.90 mg, 0.094 mmol) and diisopropylethylamine (0.025 mL, 0.142 mmol) in NMP (0.4 mL) was heated at 130 C. overnight. The reaction mixture was diluted with MeOH/H2O and purified by preparative HPLC using the conditions as shown below. Column: Waters Sunflower C-18 19*100 mm Gradient: 25-100% aqueous methanol over 10 minutes containing 0.1% TFA Flow rate: 20 mL/min Retention time: 11.3 min The resulting TFA salt was converted to the free base by passing through a SCX column to obtain 21 mg of N-cyclopropyl-3-(2-(2-phenylpyrrolidin-1-yl)pyrrolo[1,2-f][1,2,4]triazin-4-ylamino)-1H-pyrazole-5-carboxamide as a solid. MS (ESI) m/z 429.1 (M+H). 1H NMR (CD3OD) delta ppm 7.38 (s, 1H), 7.29 (s, 4H), 7.16 (s, 1H), 6.79 (d, J=3.85 Hz, 1H), 6.47 (s, 1H), 5.31 (s, 1H), 3.89 (d, J=4.12 Hz, 1H), 3.66-3.72 (m, 1H), 2.78-2.84 (m, 1H), 2.39-2.48 (m, 1H), 1.97-2.04 (m, 2H), 1.88-1.96 (m, 1H), 0.78-0.86 (m, 2H), 0.66 (br s, 2H).
  • 24
  • [ 5264-35-7 ]
  • [ 1006-64-0 ]
  • [ 916518-31-5 ]
  • 26
  • [ 39637-99-5 ]
  • [ 1006-64-0 ]
  • C20H20F3NO2 [ No CAS ]
  • 27
  • [ 20445-33-4 ]
  • [ 1006-64-0 ]
  • (2S)-2-phenylpyrrolidine-(S)-MTPA-amide [ No CAS ]
  • 30
  • [ 939-52-6 ]
  • [ 1006-64-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: NaN3 / dimethylsulfoxide / 55 °C 2: PPh3 / hexane 3: NaBH4; AcOH / methanol
Multi-step reaction with 5 steps 1: p-Toluenesulfonic acid / benzene / 5 h / Heating 2: dimethylformamide 3: 1.) KOH, 2.) HCl / 1.) ethanol/water, 6 h, reflux 4: p-Toluenesulfonic acid / benzene / Heating 5: LiAlH4 / diethyl ether / Ambient temperature
  • 31
  • [ 350479-90-2 ]
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  • 32
  • [ 316813-41-9 ]
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  • [ 316813-68-0 ]
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  • [ 316813-12-4 ]
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  • [ 316813-66-8 ]
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  • 36
  • [ 316813-29-3 ]
  • [ 1006-64-0 ]
  • 37
  • [ 316813-33-9 ]
  • [ 1006-64-0 ]
  • 38
  • 4-methyl-benzenesulfinic acid (2-benzenesulfonyl-1-phenyl-but-3-enyl)-amide [ No CAS ]
  • [ 1006-64-0 ]
  • 39
  • [ 1006-64-0 ]
  • 1,2-Bis(S)-(2-phenylpyrrolidinyl)ethane [ No CAS ]
  • 40
  • [ 174311-01-4 ]
  • [ 1006-64-0 ]
  • 41
  • Methanesulfinic acid 3-(benzyl-tert-butoxycarbonyl-amino)-propyl ester [ No CAS ]
  • [ 1006-64-0 ]
  • 42
  • [ 56139-59-4 ]
  • [ 1006-64-0 ]
  • 43
  • [ 132959-45-6 ]
  • [ 1006-64-0 ]
  • 46
  • [ 3308-99-4 ]
  • [ 1006-64-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 1.) KOH, 2.) HCl / 1.) ethanol/water, 6 h, reflux 2: p-Toluenesulfonic acid / benzene / Heating 3: LiAlH4 / diethyl ether / Ambient temperature
  • 47
  • [ 42331-15-7 ]
  • [ 1006-64-0 ]
YieldReaction ConditionsOperation in experiment
General procedure: The crude mixture was then was dissolved in 5 mL 1,2-DME, and was subsequently transferredinto another round bottom flask that had been charged with 0.14 mL SOCl2 (1.96 mmol, 2equiv.) at 0 C. The reaction mixture was stirred for 3 h at 25 C, then 1 mL aqueous 5M NaOHwas added at 0 C. After stirring for an additional 4 h at 25 C, the product was extracted withEt2O (3×15 mL), then the solvent was removed under reduced pressure. The crude product waspurified via column chromatography using NH4OH-spiked solvent to afford the desired 2-substituted pyrrolidine.
  • 48
  • [ 1006-64-0 ]
  • [ 697306-96-0 ]
  • [ 74124-79-1 ]
  • methyl (2R,3S)-3-(1H-indol-3-yl)-2-[(2-phenylpyrrolidin-1-yl)carbonyl]amino}butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine; In acetonitrile; at 0 - 20℃; for 16h; To a solution of ethyl (2R, 3S)-2-AMINO-3- (LH-INDOL-3- yl) butanoate methanesulfonate (500 mg) and triethylamine (0.233 mL) in acetonitrile (8 ML) was added N, N'- disuccinimidyl carbonate (0.429 mg) under ice-cooling and the mixture was stirred for 1 hr. To the obtained solution was added a solution of <strong>[1006-64-0]2-phenylpyrrolidine</strong> (247 mg) in acetonitrile (1 mL) under ice-cooling. The reaction solution was stirred at room temperature for 16 hrs, and 1N hydrochloric acid was added. The mixture was extracted with ethyl acetate. The extract was washed with saturated potassium carbonate solution and saturated brine and dried (NA2SO4). THE solvent was evaporated under reduced pressure and the residue was purified by aminopropyl silica gel column chromatography (developing solvent: ethyl acetate) (546 mg, yield 89%). To a solution of the obtained methyl (2R, 3S)-3-(LH-INDOL-3-YL)-2- [(2-PHENYLPYRROLIDIN-1-YL) carbonyl] amino} butanoate (546 mg) in methanol (11 mL) was added 2N aqueous sodium hydroxide (2.02 mL) at room temperature and the mixture was stirred for 16 hrs. To the reaction solution was added 1N hydrochloric acid and the mixture was extracted with ethyl acetate. The extract was dried (NA2S04) and the solvent was evaporated under reduced pressure to give the title compound as an amorphous powder (436 mg, yield 83%). LC/MS (ESI) m/z 392 (M+H+).
  • 49
  • [ 752202-08-7 ]
  • [ 1006-64-0 ]
  • [ 685872-81-5 ]
YieldReaction ConditionsOperation in experiment
A solution OF 4- (3-PIPERIDIN-1-YLPROPOXY) benzoic acid hydrochloride (D2) (299mg) in thionyl chloride (8ml) was REFLUXED for 1 H, COOLED to rt and evaporated. The acid chloride was re-evaporated from DCM (2X5ML). The residue was REDISSOLVED in DCM (15MUT) and triethylamine (0. 43ml) and added to a stirred solution of (R, S)-<strong>[1006-64-0]2-phenylpyrrolidine</strong> (147MG) in DCM (5ml) at rt. The mixture was stirred for 1H, washed with saturated sodium hydrogen carbonate solution (1 OML), water (3X10M1), dried (MGS04) and evaporated. The residue was chromatographed (silica gel, step gradient 2-7% MEOH (containing 10%. 880 ammonia solution) in DCM). Fractions containing the required product were treated with excess hydrogen chloride (4M solution in dioxan) and then concentrated to yield the title compound (E157) (332mg). MS electrospray (+ion) 393 (MH+). 1 H NMR 8 (DMSO-d6): at 353 O K 10.20 (1 H, S), 7.40 (2H, d, J=8.5Hz), 7.25 (5H, m), 6.89 (2H, d, J=8.5Hz), 5.11 (1H, m), 4.09 (2H, t, J=6.5Hz), 2.80-3. 83 (6H, m), 2.05- 2.55 (6H, m), 1.31-1. 93 (8H, m).
  • 50
  • [ 1006-64-0 ]
  • [ 676494-70-5 ]
  • 6-[4-[ (2-phenylpyrrolidin-1-yl)methyl]phenoxy]pyridine-3-carboxamide [ No CAS ]
  • 51
  • [ 1006-64-0 ]
  • [ 72934-37-3 ]
  • 1-[1-(4-chlorophenyl)cyclopropyl]carbonyl}-2-phenylpyrrolidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h; To a solution of 30 mg of 1-(4-chlorophenyl)cyclopropanecarboxylic acid and 81 mg BOP reagent in 0.5 mL methylene chloride wad added 27 mg of 2-phenylpyrrolidine, followed by the addition of 53 ul of Hunig base. The reaction mixture was stirred at r. t. for 2 hours and directly purified by flash column using ethyl/hexane as the eluting solvent to provide the desired 1-[1-(4- chlorophenyl)cyclopropyl]carbonyl}-2-phenylpyrrolidine. LCMS (ESI) : 326.1 (M+H+).
  • 52
  • [ 1006-64-0 ]
  • [ 6940-50-7 ]
  • 6-(4'-Bromophenyl)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-5-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With (1S,2R)-(+)-norphedrine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In methanol; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane; acetonitrile; 6-(4'-Bromophenyl)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-5-one (4). To a stirred solution of 4-bromomandelic acid (832 mg, 3.6 mmol), 2-phenylpyrrolidine (530 mg, 3.6 mmol), BOP reagent (benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphonate, 1.53 g, 3.6 mmol) in 25 mL of anhydrous acetonitrile was added triethylamine (1.06 mL, 7.2 mmol) at room temperature under an argon atmosphere. The reaction mixture was stirred at room temperature for 4 h, concentrated under reduced pressure, then dissolved in methylene chloride (50 mL). The methylene chloride solution was washed with 1N HCl solution, water, saturated sodium bicarbonate solution, water, brine, and dried over anhydrous MgSO4, concentrated under reduced pressure to afford a syrup in a flask. PPA (polyphosphoric acid, 10 g) was added to the flask. The reaction mixture was heated on a rotavap in boiling water bath for 1 h, cooled to room temperature, solubilized in ice water, extracted with methylene chloride (4*15 mL). The methylene chloride extract was washed with saturated sodium bicarbonate solution, water, brine, and dried over anhydrous MgSO4, concentrated under reduced pressure to afford a crude product mixture. Flash chromatography (silica gel, 0.5% MeOH, 0.01% Et3 N in methylene chloride) to afford 860 mg of 4 (70% yield for two steps) as a mixture of trans and cis isomers with trans to cis ratio 2:1 (estimated by 1 H NMR integration). Recrystallization with THF isolated trans isomer as a yellow solid, mp 204-206 C. 1 H NMR (CDCl3) delta 1.96-2.22 (m, 3H, C2H2 & C1H), 2.66-2.78 (m, 1H, C1H), 3.48-3.58 (m, 1H, C3H), 3.732 (dd, 1H, J=7.5, 11.7 Hz, C3H), 4.610 (s, 1H, C6H), 4.64-4.70 (m, 1H, C10bH), 6.591 (d, 1H, J=7.8 Hz, aryl), 7.104 (d, 2H, J=8.1 Hz, C6 phenyl aryl), 7.12-7.28 (m, 3H, 8, 9, aryl), 7.520 (d, 2H, J=8.4 Hz, C6 phenyl aryl); 13 C NMR (CDCl3) delta 23.06 (C2), 31.21 (C1), 45.07 (C3), 52.99 (C10b), 58.62 (C6), 121.10 (C4'), 123.58 (aromatic), 126.74 (aromatic), 127.38 (aromatic), 131.38 (aromatic), 132.60 (aromatic), 136.15 (aromatic), 136.55 (aromatic), 136.79 (aromatic), 167.36 (C5). HRMS calculated 341.0415 (for C18 H16 NOBr), measured 341.0427 (relative error 3.4 ppm).
  • 53
  • [ 796600-15-2 ]
  • [ 1006-64-0 ]
  • 2-chloro-3-methyl-4-(2-phenyl-pyrrolidin-1-yl)-benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With 4-methyl-morpholine; at 150℃; Heat <strong>[796600-15-2]2-chloro-4-fluoro-3-methyl-benzonitrile</strong> (144 mg, 0.85 mmol) and 2- . phenyl-pyrrolidine (0.15 g, 1.02 mmol, 1.20 equivalents) in N-methylmorpholine (0.11 ml, 1.02 mmol, 1.20 equivalents) at 150 0C overnight. Allow the reaction mixture to cool to room temperature, dilute with dichloromethane (1 ml), load on silica, and purify by chromatography (12 g silica gel, 0 to 100% ethyl acetate/hexanes over 20 minutes) to obtain 150 mg of an oily residue. Recrystallize from ethyl acetate/hexanes to obtain the title compound (92 mg, 37%). LCMS(APCI+): 297.0 (M+l)+; 1H NMR (400 MHz, CDCl3): delta 7.25 (s, 2H), 7.19 (m, 2H), EPO <DP n="58"/>6.65 (d, IH), 4.70 (m, IH), 4.06 (m, IH), 3.18 (m, IH), 2.44 (m, IH), 2.43 (s, 3H), 2.12 (m, IH), 1.94 (m, 2H).
  • 54
  • [ 1006-64-0 ]
  • [ 919346-88-6 ]
  • 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-{5-[(2-phenyl-1-pyrrolidinyl)methyl]-3-thienyl}-1H-indole-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% With sodium tris(acetoxy)borohydride; In dimethyl sulfoxide; Example 46 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-{5-[(2-phenyl-1-pyrrolidinyl)methyl]-3-thienyl}-1H-indole-7-carboxamide To a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide (50 mg, 0.11 mmol) in DMSO (2.0 mL) was added <strong>[1006-64-0]2-phenylpyrrolidine</strong> (147 mg, 1.0 mmol). The reaction mixture was then reacted in a microwave at 120 C. for 10 min. Sodium triacetoxyborohydride (220 mg, 1.0 mmol) was then added and the reaction was reacted at room temperature overnight. It was then purified by Gilson Preparatory HPLC to give 14.0 mg of the title compound (22%). LC/MS=m/z 577.2 [M+H] Ret. Time: 1.65 min.
22% Example 46: 3-H -(ethylsulf onyl)-4-piperidinv?-5-l5-r(2-phenyl-1 - pyrrolidinyl)methv?-3-thienyl}-1 H-indole-7-carboxamide; To a solution of 3-[1 -(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-3-thienyl)-1 H-indole-7- carboxamide (50 mg, 0.11 mmol) in DMSO (2.0 ml_) was added <strong>[1006-64-0]2-phenylpyrrolidine</strong> (147 mg, 1.0 mmol). The reaction mixture was then reacted in a microwave at 120 C for 10 min. Sodium triacetoxyborohydride (220 mg, 1.0 mmol) was then added and the reaction was reacted at room temperature overnight. It was then purified by Gilson Preparatory HPLC to give 14.0 mg of the title compound (22 %). LC/MS = m/z 577.2 [M+H] Ret. Time: 1.65 min.
  • 55
  • [ 1006-64-0 ]
  • [ 488838-94-4 ]
  • [ 1158829-00-5 ]
YieldReaction ConditionsOperation in experiment
44% With caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl;palladium diacetate; In toluene; at 95℃; for 16h; Add 3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (prepared essentially as described in Preparation 36) (500 mg, 1.28 mmol), <strong>[1006-64-0]2-phenyl-pyrrolidine</strong> (227 mg, 1.54 mmol), palladium acetate (29 mg, 0.128 mmol), racemic 2,2'-bis(diphenylphosphino)-1,1'-binapthyl (239 mg, 0.384 mmol) and cesium carbonate (584 mg, 1.79 mmol) to toluene (5 mL) and stir for 16 h at 95 C. Cool the reaction to RT, and dilute with EtOAc (60 mL). Filter the slurry and concentrate the filtrate. Chromatograph the residue on silica gel, eluting with 0:100-15:85 EtOAc:hexanes to give the crude product (220 mg, 44%) as a yellow oil. Dissolve the crude residue in 4 M HCl in dioxane (10 mL) and stir the reaction at RT for 1 h. Concentrate the reaction and subject the residue to SCX ion exchange chromatography to give 160 mg of freebase material. Dissolve the residue in methanol (5 mL) and add succinic acid (1 eq.) concentrate the solution, slurry in diethyl ether, filter and dry the residue under vacuum to isolate the title compound as an off white solid (160 mg, 30%).MS (ES): m/z=293.1 [M+H].
  • 56
  • [ 1006-64-0 ]
  • [ 1112980-26-3 ]
  • [ 1112981-96-0 ]
  • N-(6-(2-((2S)-2-phenyl-1-pyrrolidinyl)-4-pyrimidinyl)-1,3-benzothiazol-2-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 140℃;Microwave irradiation; Example 266; N-(6-(2-(2-phenylpyrrolidin-1-yI)pyrimidin-4-yl)benzo[d]thiazoI-2-yl)acetamide; A mixture of N-(6-(2-chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (0.100 g, 0.3 mmol), 2- phenylpyrrolidine (0.05 ml, 0.3 mmol), diisopropylethylamine (0.1 ml, 0.7 mmol) in DMSO (1.0 g, 1 1 mmol) was heated under CEM microwave at 140 C, 130 W (Powermax off). The resultant was diluted with 5 ml of water and filtered. The solid was diluted with DCM and filtered. The filterate was recrystallized from DCM to give a brown solid (25 mg). MS (ESI pos. ion) Found m/z: 416, (M+H)+.
  • 57
  • [ 1006-64-0 ]
  • [ 1173977-37-1 ]
  • [ 1173976-73-2 ]
YieldReaction ConditionsOperation in experiment
41% To a solution of [(4-chlorophenyl)-(3-methoxy-benzenesulfonyl)-amino]-acetic acid (250 mg, 0.7 mmol) in dry dichloromethane (20 mL) were sequentially added EDCI (202 mg, 1.05 mmol), HOBT (142.4 mg, 1.05 mmol), and DIPEA (0.23 mL, 1.40 mmol). The reaction mixture was allowed to stir for 30 minutes under nitrogen at 25 C. 2-Phenyl-pyrrolidine (104 mg, 0.7 mmol) was added and the mixture was stirred at 25 C. for 12 h. The reaction mixture was diluted with dichloromethane (20 mL), washed with saturated aqueous ammonium chloride solution, saturated aqueous sodium bicarbonate solution and water. The organic layer was dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by column chromatography over silica gel (30-40% ethyl acetate/hexane) to yield the title compound.Yield: 140 mg (41%). HPLC purity 98.17%; MS (m/e): 485.4 (M++H); 1H-NMR (DMSO-d6, 400 MHz): delta1.76 (m, 1H), 1.85 (m, 3H), 2.32 (m, 1H), 3.45 (m, 1H), 3.78 (s, 3H), 4.77 (m, 3H), 6.93 (m, 3H), 7.19 (m, 6H), 7.43 (m, 4H).
  • 59
  • [ 1006-64-0 ]
  • [ 1210859-12-3 ]
  • [ 1210854-38-8 ]
  • [ 1210854-38-8 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; HATU; In dichloromethane; at 20℃; Example 15; A. 3-Phenylamino-1-[(2RS*)2-phenyl-pyrrolidin-1-yl]-(2RS*)-2-(4-trifluoromethyl-phenyl)-propan-1-one. To Compound 14b (90 mg, 0.29 mmol) and Et3N (0.32 mL, 2.32 mmol) in CH2Cl2 (1.2 mL) was added racemic <strong>[1006-64-0]2-phenylpyrrolidine</strong> (67 mg, 0.37 mmol) and HATU (221 mg, 0.58 mmol) and the reaction mixture was stirred at rt overnight. The reaction mixture was partitioned between CH2Cl2 and saturated aqueous NaHCO3, the organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give Compound 15a as a mixture of four stereoisomers. The mixture of four diastereomers was dissolved in DMF, and upon standing a precipitate formed. The precipitate was removed by filtration and the leftover supernatant was purified by HPLC (C-18, 10-100 MeCN in water gradient) to give Compound 130 as a mixture of two stereoisomers. MS 439.1 (M+1)+.
  • 60
  • [ 1207729-66-5 ]
  • [ 1006-64-0 ]
  • 61
  • (-)-(S)-2-Phenylpyrrolidine hydrochloride [ No CAS ]
  • [ 1006-64-0 ]
  • 62
  • [ 1006-64-0 ]
  • [ 189321-65-1 ]
  • C26H39N3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 1-(tert-butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: 2-(phenyl)pyrrolidine In N,N-dimethyl-formamide
  • 63
  • [ 1006-64-0 ]
  • [ 53120-53-9 ]
  • [ 1257520-42-5 ]
YieldReaction ConditionsOperation in experiment
63% With N-ethyl-N,N-diisopropylamine; In dichloromethane; EXAMPLE 7 2-adamantyl <strong>[1006-64-0]2-phenylpyrrolidine</strong>-1-carboxylate; A vial equipped with a flea stir bar was charged with <strong>[1006-64-0]2-phenylpyrrolidine</strong> (17 mg, 0.12 mmol), i-Pr2NEt (0.031 mL, 0.17 mmol). A solution of 2-adamantyl chloroformate (25 mg, 0.12 mmol) in CH2CI2 (1.5 mL) was added. The mixture was stirred over the weekend and applied to a 10-mL ChemElut cartridge prewetted with 5% aq HCI (5 mL). The cartridge was eluted with ether (20 mL). The eluate was concentrated and the residue was purified by prep HPLC to afford the title compound (24 mg, 63%). LC-MS Method 2 tR = 11.81 min, m/z = 326, 1H NMR (CDCI3) 0.92 (m, 1 H), 1.03 (m, 1 H), 1.30-2.20 (14H), 2.32 (m, 1 H), 2.50 (br s, 1 H), 3.64 (m, 2H), 4.70-5.10 (2H), 7.18 (m, 3H), 7.28 (m, 2H).
  • 66
  • [ 1294455-04-1 ]
  • [ 1006-64-0 ]
  • 67
  • [ 1294455-05-2 ]
  • [ 1006-64-0 ]
  • 68
  • [ 56553-09-4 ]
  • [ 1006-64-0 ]
YieldReaction ConditionsOperation in experiment
87% With lithium aluminium tetrahydride; In tetrahydrofuran; at -5 - 20℃; for 2h; (4) (S)-5-phenylpyrrolidin-2-one (40 g, 0.25 mol) was dissolved in tetrahydrofuran (800 mL), cooling to -5-5 deg. C, lithium aluminum hydride (23.6 g, 0.62 mol) was added in portions to keep the internal temperature below 10 C, and the mixture was stirred at room temperature for 2 h. Quenched with water (23.6 g), keeping the temperature within -5-5 deg. C, followed by stirring at room temperature for 1 h, filtered, and concentrated to give 32 g of a colorless oil, in 87% yield.
  • 69
  • (5S)-1-[(1R)-2-hydroxy-1-phenylethyl]-5-phenyl-2-pyrrolidone [ No CAS ]
  • [ 1006-64-0 ]
  • 70
  • [ 1006-64-0 ]
  • [ 4887-88-1 ]
  • [ 1276023-84-7 ]
YieldReaction ConditionsOperation in experiment
27% 5(6)-Bromobenzimidazole (200 mg; 1 mmol; 1 eq.), the respective pyrrolidine derivative (1.2 mmol; 1.2 eq.), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (9 mg; 0.024 mmol; 0.024 eq.; 2.4 mol %) and Pd2 dba3 (9 mg; 0.01 mmol; 0.01 eq.; 1 mol %) were dissolved in THF (1 ml). After addition of lithiumbis(trimethylsilyl)amide (1 M solution in THF; 2.2 ml; 2.2 mmol; 2.2 eq.) the mixture was stirred under argon-atmosphere at 65 C. for 24 h. After cooling to room temperature, 2 N HCl was added until acidic pH and stirred for additional 10 min. The mixture was poured into saturated sodium bicarbonate solution (20 ml) and extracted with EtOAc (3×25 ml). The combined organic layers were dried over Na2SO4 and evaporated. The remaining residue was purified by flash-chromatography using Al2O3 and a CHCl3/MeOH gradient. Example 1015-(2-phenylpyrrolidin-1-yl)-1H-benzo[d]imidazoleThe compound was synthesized according to method 8 starting from <strong>[4887-88-1]5(6)-bromobenzimidazole</strong> (200 mg; 1 mmol; 1 eq.), 2-dicyclohexylphosphino-2'-(N, N-dimethylamino)biphenyl (9 mg; 0.024 mmol; 0.024 eq.; 2.4 mol %), Pd2 dba3 (9 mg; 0.01 mmol; 0.01 eq.; 1 mol %) and 4-phenylpyrrolidine (176 mg; 1.2 mmol; 1.2 eq.); yield: 0.071 g (27.0%); MS m/z: 264.4 [M+H]+; 1H-NMR (DMSO d6, 500 MHz): delta 1.76-1.81 (m, 1H); 1.93-1.98 (m, 2H); 2.35-2.44 (m, 1H); 3.34-3.39 (m, 1H); 3.71-3.75 (m, 1H); 4.73-4.75 (m, 1H); 6.39 (br s, 1H); 6.42-6.44 (m, 1H); 7.17-7.35 (m, 6H); 7.83 (s, 1H); 11.80 (br s, 1H); HPLC ([A]): rt 13.23 min (95.7%)
  • 71
  • [ 1006-64-0 ]
  • (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride [ No CAS ]
  • [ 1309205-45-5 ]
YieldReaction ConditionsOperation in experiment
17% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 24h; Example 76-[(lE)-3-Oxo-3-(2-phenylpyrrolidin-l-yl)prop-l-en-l-yl]-3 4-dihydro- l,8-naphthyridin-2( lH)-one (E7)A 16 ml_ vial flask was successively charged with (2E)-3-(7-oxo-5,6,7,8-tetrahydro- l,8-naphthyridin-3-yl)acrylic acid hydrochloride (30 mg, 0.12 mmol), DMF (3 ml_), <strong>[1006-64-0]2-phenylpyrrolidine</strong> (21 mg, 0.14 mmol), DIPEA (48 muIota_, 0.28 mmol) and EDAC (27 mg, 0.14 mmol). The reaction mixture was stirred at room temperature and concentrated to dryness. LC/MS showed the presence of the target compound and no starting material after 24 h. The residue was purified on preparative TLC (eluent: dichloromethane/NH3 7N in MeOH, 2.5%) to give a pale yellow solid . This solid as triturated in acetone, filtered, washed with acetone and dried to give the title compound (7 mg, 17%) as a white solid.LCMS (ESI+) m/z 348 (M + H)+: 100%.*H NMR (DMSO-c/e, 300 MHz) : delta (ppm) : 10.73-10.49 (m, 1H), 8.41-8.35 (m, 0.5H), 8.19-8.05 (m, 1H), 7.66-7.56 (m, 0.5H), 7.48-7.00 (m, 6.5H), 6.58 (d, J = 15.3 Hz, 0.5H), 5.46-5.09 (m, 1H), 4.05-3.55 (m, 2H), 2.99-2.77 (m, 2H), 2.01-1.61 (m, 4H). The other CH2 is hidden by DMSO signal.
  • 72
  • [ 1006-64-0 ]
  • [ 25026-34-0 ]
  • [ 1312573-19-5 ]
  • 73
  • [ 1006-64-0 ]
  • [ 1217335-44-8 ]
  • [ 1217334-42-3 ]
YieldReaction ConditionsOperation in experiment
78% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; 2-Phenylpyrrolidine (20 mg, 0.14 mmol) was added to a stirred suspension of 3-(2-(4-fluorophenyl)-3- (methylcarbamoyl)benzofuran-5-yl)benzoic acid (20 mg, 0.051 mmol), HATU (25 mg, 0.066 mmol), and DIPEA (50 mu, 0.29 mmol) in DMF (0.5 mL). The reaction was stirred at r.t. overnight. The reaction was then diluted with MeOH, filtered, and purified by prep HPLC. Concentration afforded the title compound (21 mg, 78% yield) as a light pink solid. XH NMR (-3:2 ratio of amide rotamers, 500 MHz, DMSO-i¾) delta ppm 8.44 - 8.56 (m, 1 H) 7.96 - 8.07 (m, 2 H) 7.74 - 7.89 (m, 3 H) 7.56 - 7.67 (m, 2 H) 7.30 - 7.45 (m, 5.4 H) 7.16 - 7.29 (m, 2.6 H) 7.09 (d, J= 7.02 Hz, 1 H) 5.19 (t, J= 6.71 Hz, 0.6 H) 4.98 (d, J= 6.41 Hz, 0.4 H) 3.75 - 3.92 (m, 1.4 H) 3.53 - 3.64 (m, 0.6 H) 2.87 (m, 3 H) 2.40 (dd, J= 12.36, 6.56 Hz, 0.6 H) 2.30 - 2.38 (m, 0.4 H) 1.73 - 1.92 (m, 3 H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A = 10% CH3CN/90% H2O/0.1% TFA, solvent B = 90% CH3CN/10% H2O/0.1% TFA, start %B = 0, final %B = 100, gradient time = 3 min, stop time = 4 min, flow rate = 4 ml/min, column: Sunfire C18 5 muiotaeta 4.6 x 50 mm; HPLC Rt = 1.86 min, (ES+) m/z (MH+) = 519. Analytical HPLC method: solvent A = 5%CH3CN/95% H2O/0.1% TFA, solvent B = 95% CH3CN/5% H2O/0.1% TFA, start %B = 10, final %B = 100, gradient time = 15 min, stop time = 18 min, flow rate = 1 ml/min. Column: Waters Sunfire C-18, 3.5 muiotaeta 4.6 x 150 mm, Rt = 14.38 min, purity = 99%; column: Waters Xbridge Phenyl column 3.5 muiotaeta 4.6 x 150 mm, Rt = 13.01 min, purity = 99%.
  • 74
  • [ 1006-64-0 ]
  • [ 1314874-80-0 ]
  • [ 1360612-76-5 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 180℃;Microwave irradiation; General Procedure for nucleophilic aromatic Substitution 3To a microwave vial stir bar is added 1 eq. of triazolopyrazine, 1.1 eq. of the corresponding amine and potassium carbonate (2 eq). N,N-dimethylformamide (3 mL / mmol) is added and the suspension heated in the microwave at 180C. The reaction is monitored by HPLC. Upon completion, the mixtured is diluted with ethylacetate, filtered over Celite and concentrated. The residue is purified via column chromatography or preparative HPLC.(3,5-Dimethoxy-phenyl)-[8-(2-phenyl-pyrrolidin-1-yl)-[1,2,4]triazolo[1 ,5- a]pyrazin-2- l]-amine ("D19")Step 1 :The reaction is performed using general procedure 3 and rac-2-phenyl- pyrrolidine as coupling partner.
  • 75
  • [ 1006-64-0 ]
  • [ 67754-03-4 ]
  • [ 1380753-26-3 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol;Reflux; Description 72: methyl 5-chloro-2-(2-phenylpyrrolidin-1-yl)nicotinate (D72)To a solution of <strong>[67754-03-4]Methyl 2,5-dichloronicotinate</strong> (120 mg, 0.58 mmol, ) in isopropanol (10ml), 2-phenylpyrrolidine (86 mg, 0.58 mmol, available from Matrix Scientific No. 018619) and N,N-Diisopropylethylamine (90 mg, 0.70 mmol) were added. The mixture was heated under reflux overnight. After cooling to room temperature, the mixture was evaporated and the residue was dissolved in ethyl acetate (10ml), washed with water (10ml) and brine (10ml), dried over Na2S04 and evaporated in vacuo. The crude residue was purified by flash chromatography on silica gel eluting with a mixture petroleum ether/ethyl acetate 20:1 to afford the title compound (D72) (167 mg) as colorless oil.1 H NMR (400MHz , CHLOROFORM-d) delta (ppm): 8.10 (1 H, d, J= 2.4 Hz), 7.79 (1 H, d, J= 2.4 Hz), 7.28 - 7.18 (5H, m), 5.36 - 5.32 (1 H, m), 3.95 - 3.89 (1 H, m), 3.85 (3H, s), 3.33 - 3.28 (1 H, m), 2.52 - 2.47 (1 H, m), 2.07 - 2.04 (1 H, m), 1 .92 - 1 .89 (2H, m)
167 mg With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol;Reflux; To a solution of <strong>[67754-03-4]Methyl 2,5-dichloronicotinate</strong> (120 mg, 0.58 mmol,) in isopropanol (10 ml), 2-phenylpyrrolidine (86 mg, 0.58 mmol, available from Matrix Scientific 018619) and N,N-Diisopropylethylamine (90 mg, 0.70 mmol) were added. The mixture was heated under reflux overnight. After cooling to room temperature, the mixture was evaporated and the residue was dissolved in ethyl acetate (10 ml), washed with water (10 ml) and brine (10 ml), dried over Na2SO4 and evaporated in vacuo. The crude residue was purified by flash chromatography on silica gel eluting with a mixture petroleum ether/ethyl acetate 20:1 to afford the title compound (D72) (167 mg) as colorless oil.
  • 76
  • [ 764-93-2 ]
  • [ 1006-64-0 ]
  • [ 100-52-7 ]
  • [ 1376191-20-6 ]
  • 77
  • [ 1376191-46-6 ]
  • [ 1006-64-0 ]
  • 78
  • [ 1376191-20-6 ]
  • [ 1006-64-0 ]
  • 80
  • [ 1006-64-0 ]
  • [ 1179523-32-0 ]
  • 81
  • [ 4850-50-4 ]
  • [ 1006-64-0 ]
  • 82
  • [ 99512-38-6 ]
  • [ 1006-64-0 ]
  • 83
  • [ 1006-64-0 ]
  • [ 1369487-49-9 ]
  • [ 1401619-01-9 ]
YieldReaction ConditionsOperation in experiment
30% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 18h; The following was added sequentially to DCM (2 mL): 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid (50 mg, 0.126 mmol), DIPEA (0.07 mL, 0.378 mmol), EDC (30 mg, 0.151 mmol), HOBT (24 mg, 0.151 mmol), and <strong>[1006-64-0]2-phenylpyrrolidine</strong> (0.023 mL, 0.151 mmol). The mixture was stirred for 18 h at rt, at which time the solution diluted with a 1:1 solution of ethyl acetate:diethyl ether and washed with 1M HCl (1*), 10% aq. sodium carbonate (1*) and brine (1*). The organic phase was dried with magnesium sulfate and concentrated in vacuo. The resulting residue was dissolved in EtOAc and precipitated out hexanes, and then collected over a filter and washed with diethyl ether to give the title compound as a white solid. (Yield: 20 mg, 0.038 mmol, 30%) 1H NMR (400 MHz, CDCl3) 7.61, 7.43-7.05, 7.09-6.94, 6.58, 5.41, 5.06-4.82, 4.33, 3.83-3.60, 3.11-2.88, 2.50-2.22, 2.06-1.58, 1.16-0.82
  • 84
  • [ 1163790-67-7 ]
  • [ 1006-64-0 ]
  • [ 1163793-61-0 ]
  • 85
  • [ 700-91-4 ]
  • [ 109-72-8 ]
  • [ 694-53-1 ]
  • [ 1006-64-0 ]
YieldReaction ConditionsOperation in experiment
95% With 2,2?-Bis[(1H-inden-3?-yl)-hexanyl]titaniumdichloride; In tetrahydrofuran; at 60℃; for 3h;Inert atmosphere; The chosen metallocene (2 mol% referring to the imine) was dissolved in anh. THF (2 mL) in a dry Schlenk flask under an argon atmosphere. In the order, n-BuLi (5 mol equiv. to catalyst), phenylsilane (5 mol equiv. to catalyst) and the imine were added,and the mixture was heated to 60 C. The reaction progress was monitored via GC until no further reaction progress could be determined. Then the mixture was allowed to cool to r.t., opened to air, and quenched with diethyl ether and HCl (1 M) until pH 2was reached. The biphasic mixture was stirred for 20 min, thelayers were separated, and the organic phase washed with HCl.The combined aqueous fractions were neutralized with NaOH and extracted three times with diethyl ether. The combined organic layers were dried over Na2SO4, filtered and reducedin vacuo
93% With 2,2?-bis[(1H-inden-3?-yl)-hex-5-enyl]titaniumdichloride; In tetrahydrofuran; at 60℃; for 3h;Inert atmosphere; The chosen metallocene (2 mol% referring to the imine) was dissolved in anh. THF (2 mL) in a dry Schlenk flask under an argon atmosphere. In the order, n-BuLi (5 mol equiv. to catalyst), phenylsilane (5 mol equiv. to catalyst) and the imine were added,and the mixture was heated to 60 C. The reaction progress was monitored via GC until no further reaction progress could be determined. Then the mixture was allowed to cool to r.t., opened to air, and quenched with diethyl ether and HCl (1 M) until pH 2was reached. The biphasic mixture was stirred for 20 min, thelayers were separated, and the organic phase washed with HCl.The combined aqueous fractions were neutralized with NaOH and extracted three times with diethyl ether. The combined organic layers were dried over Na2SO4, filtered and reducedin vacuo
91% With 2,2?-Bis[(1H-inden-3?-yl)-hex-5-enyl]titanium binaphtholate; In tetrahydrofuran; at 60℃; for 3h;Inert atmosphere; The chosen metallocene (2 mol% referring to the imine) was dissolved in anh. THF (2 mL) in a dry Schlenk flask under an argon atmosphere. In the order, n-BuLi (5 mol equiv. to catalyst), phenylsilane (5 mol equiv. to catalyst) and the imine were added,and the mixture was heated to 60 C. The reaction progress was monitored via GC until no further reaction progress could be determined. Then the mixture was allowed to cool to r.t., opened to air, and quenched with diethyl ether and HCl (1 M) until pH 2was reached. The biphasic mixture was stirred for 20 min, thelayers were separated, and the organic phase washed with HCl.The combined aqueous fractions were neutralized with NaOH and extracted three times with diethyl ether. The combined organic layers were dried over Na2SO4, filtered and reducedin vacuo
90% With 2,2?-bis[(1H-inden-3?-yl)-hex-5-enyl]titaniumdichloride; In tetrahydrofuran; at 60℃; for 3h;Inert atmosphere; The chosen metallocene (2 mol% referring to the imine) was dissolved in anh. THF (2 mL) in a dry Schlenk flask under an argon atmosphere. In the order, n-BuLi (5 mol equiv. to catalyst), phenylsilane (5 mol equiv. to catalyst) and the imine were added,and the mixture was heated to 60 C. The reaction progress was monitored via GC until no further reaction progress could be determined. Then the mixture was allowed to cool to r.t., opened to air, and quenched with diethyl ether and HCl (1 M) until pH 2was reached. The biphasic mixture was stirred for 20 min, thelayers were separated, and the organic phase washed with HCl.The combined aqueous fractions were neutralized with NaOH and extracted three times with diethyl ether. The combined organic layers were dried over Na2SO4, filtered and reducedin vacuo
8% With 2,2?-bis[(1H-inden-3?-yl)-hex-5-enyl]titaniumdichloride; In tetrahydrofuran; at 60℃; for 3h;Inert atmosphere; The chosen metallocene (2 mol% referring to the imine) was dissolved in anh. THF (2 mL) in a dry Schlenk flask under an argon atmosphere. In the order, n-BuLi (5 mol equiv. to catalyst), phenylsilane (5 mol equiv. to catalyst) and the imine were added,and the mixture was heated to 60 C. The reaction progress was monitored via GC until no further reaction progress could be determined. Then the mixture was allowed to cool to r.t., opened to air, and quenched with diethyl ether and HCl (1 M) until pH 2was reached. The biphasic mixture was stirred for 20 min, thelayers were separated, and the organic phase washed with HCl.The combined aqueous fractions were neutralized with NaOH and extracted three times with diethyl ether. The combined organic layers were dried over Na2SO4, filtered and reducedin vacuo

  • 86
  • [ 1426540-43-3 ]
  • [ 1006-64-0 ]
  • C44H67N3O12 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In acetonitrile; at 50℃;Inert atmosphere; General procedure: Intermediate 3 (24 g, 30.08 mmole) was dissolved in anhydrous MeCN (1200 mL), followed by addition of R(+)-3-(4,4-dimethylpyrrolidin-2-yl) pyridine (+)-phencyphos salt (15.11 g. 36.10 mmol, 1.2 eq) and TEA (10.5 mL, 75.20 mmol, 2.5 eq) in a 2-L round bottom flask. The mixture was heated to 50 deg C overnight. The reaction mixture was then concentrated to dryness and dissolved in MeOH (1200 mL) and TEA (4 mL, 1eq) and stirred to 50 deg C overnight to remove the acetyl group. The mixture was then concentrated to dryness, dissolved in DCM (300 mL) and aq saturated bicarbonate (300mL) and extracted with DCM (4 x 300 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to dryness to afford 25g of crude product. Silica gel chromatography (0-7% MeOH/DCM) yielded final product 4f (12.5 g, 50%)
  • 87
  • [ 1210858-97-1 ]
  • [ 1006-64-0 ]
  • [ 1210854-81-1 ]
  • 88
  • [ 1006-64-0 ]
  • [ 102-92-1 ]
  • [ 1417576-33-0 ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 1h; General procedure: A solution of the cinnamic acid (5.0 mmol) and oxalyl chloride(5.5 mmol) in DCM (50 mL) and 2 drops of DMF was stirred at roomtemperature for 2 h, until evolution of CO2 had ceased. The DCMwas removed by rotary evaporation, the residue dissolved in CHCl3(30 mL) and the CHCl3 removed by rotary evaporation to removeany excess oxalyl chloride. The residue was dissolved in DCM(20 mL) and added to a stirred solution of the benzylamine(6.5 mmol) and triethylamine (7.0 mmol) in DCM (100 mL) at 0 C.The reaction was stirred at room temperature for 1 h, washed with2 M aq HCl (30 mL), water (30 mL) and 2 M aq K2CO3 (30 mL) anddried (MgSO4). Removal of the solvent gave a solid, which wasrecrystallised from EtOAc/petroleum ether. Obtained as a white solid (84%yield) m.p. 137-139 oC isolated as a 2:1 mixture of rotamers; 1H-NMR (500 MHz) delta = 1.85 - 2.10 (3H, m), 2.26 - 2.35(0.33H, m), 2.39 - 2.50 (0.67H, m), 3.77 - 3.96 (2H, m), 5.15 (0.67H, dd, J = 2.3, 7.7 Hz), 5.35 (0.33H, dd, J = 2.6, 7.7 Hz), 6.41 (0.67H, d, J = 15.5 Hz), 6.84 (0.33H, d, J = 15.5 Hz), 7.17 - 7.41 (9.33H, m),7.54 (0.67H, d, J = 7.4 Hz), 7.62(0.67H, d, J = 15.5 Hz), 7.71 (0.33H,d, J = 15.5 Hz); 13C-NMR + DEPT (125 MHz) delta = Major rotamer: 21.9 (CH2),36.5 (CH2), 47.4 (CH2), 61.6 (CH), 119.3 (CH), 125.6(CH), 127.4 (CH), 128.0 (CH), 128.9 (CH), 129.9 (CH), 135.3 (C), 141.7 (CH),143.7 (C), 165.7 (C), Minor rotamer: 23.9 (CH2), 34.1 (CH2),47.7 (CH2), 60.9 (CH), 118.7 (CH), 127.8 (CH), 128.7 (CH), 125.6 (CH), 126.7(CH), 128.5 (CH), 129.0 (CH), 129.7 (CH), 135.4 (C), 142.7 (CH), 143.0 (C),164.8 (C); nmax (solid)1644, 1593, 1420, 988, 982, 860, 762, 754, 703, 679 cm-1;.LRMS (EI) 277, 146, 131, 103; HRMS(EI) M+, found 277.1458, C19H19NO requires 277.1461.
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