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[ CAS No. 19131-99-8 ] {[proInfo.proName]}

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Product Details of [ 19131-99-8 ]

CAS No. :19131-99-8 MDL No. :MFCD00067113
Formula : C9H13N Boiling Point : -
Linear Structure Formula :- InChI Key :RCSSHZGQHHEHPZ-QMMMGPOBSA-N
M.W : 135.21 Pubchem ID :2060073
Synonyms :

Calculated chemistry of [ 19131-99-8 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.33
Num. rotatable bonds : 2
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 43.82
TPSA : 12.03 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.92 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.23
Log Po/w (XLOGP3) : 1.69
Log Po/w (WLOGP) : 1.64
Log Po/w (MLOGP) : 2.19
Log Po/w (SILICOS-IT) : 2.01
Consensus Log Po/w : 1.95

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.05
Solubility : 1.19 mg/ml ; 0.00881 mol/l
Class : Soluble
Log S (Ali) : -1.56
Solubility : 3.75 mg/ml ; 0.0277 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.24
Solubility : 0.078 mg/ml ; 0.000577 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 19131-99-8 ]

Signal Word:Danger Class:8
Precautionary Statements:P210-P261-P264-P270-P271-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P362+P364-P370+P378-P403+P235-P405-P501 UN#:2735
Hazard Statements:H227-H302+H312+H332-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 19131-99-8 ]

* 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 [ 19131-99-8 ]

[ 19131-99-8 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 2627-86-3 ]
  • [ 19131-99-8 ]
YieldReaction ConditionsOperation in experiment
ueber mehrere Stufen;
Multi-step reaction with 2 steps 1: 18 h / 51 °C 2: 90 g / LiAlH4 / tetrahydrofuran / 8 h / 63 °C
Multi-step reaction with 2 steps 1: 56 percent / Et3N / CH2Cl2 / 1 h / 5 - 20 °C 2: 75 percent / LiAlH4 / tetrahydrofuran / 1 h / Heating
Multi-step reaction with 2 steps 1: 99 percent / K2CO3 / tetrahydrofuran / 0 deg C, 2 h, then 25 deg C, 6 h 2: 91 percent / LiAlH4 / tetrahydrofuran / 7 h / 25 °C
Multi-step reaction with 2 steps 1: 100 percent / toluene / 15 h / Heating 2: 89 percent / LiAlH4 / tetrahydrofuran / 96 h / Ambient temperature
Multi-step reaction with 2 steps 1: Et3N / diethyl ether / 0.5 h / Ambient temperature 2: lithium aluminium hydride / tetrahydrofuran / 2 h / Heating
Multi-step reaction with 2 steps 2: LiAlH4

  • 2
  • [ 19145-06-3 ]
  • [ 19131-99-8 ]
YieldReaction ConditionsOperation in experiment
89% With lithium aluminium tetrahydride In tetrahydrofuran for 96h; Ambient temperature;
With lithium aluminium tetrahydride
90 g With lithium aluminium tetrahydride In tetrahydrofuran at 63℃; for 8h;
70 g (78%) With sodium hydroxide; LiAlH4 In tetrahydrofuran a.b EXAMPLES OF COMPOUNDS FROM CHART E-CHART EX1 STEP 1(b) of CHART EX1. Synthesis of N-Methyl-N-(S)-1-phenylethylamine, EX1(b'). Add powdered LiAlH4 (50 g) and THF (500 mL) to a 3000 ml flask. Then add a solution of N-formyl-N-(S)-1-phenylethylamine (EX11(b'), 100 g) in THF (500 mL) dropwise into the LiAlH4 solution. Heat the solution to reflux and stir 5 hours. After reflux, cool the solution to 5° C. and slowly quench the reaction with 10% NaOH (500 mL), then extract the product with MTBE (1*2 L). Remove the solvent in vacuo, and purify the product by distillation to yield 70 g (78%) of N-methyl-N-(S)-1-phenylethylamine. 13 C-NMR (CDCl3, ppm δ) 24.15, 34.76, 60.49, 126.84, 127.14, 128.65, 145.64.
With lithium aluminium tetrahydride

  • 3
  • [ 19131-99-8 ]
  • [ 137792-50-8 ]
  • [ 122873-90-9 ]
  • [ 122873-91-0 ]
YieldReaction ConditionsOperation in experiment
1: 30% 2: 34% With n-butyllithium In tetrahydrofuran at -78℃; for 5h;
  • 4
  • [ 19131-99-8 ]
  • [ 1011534-42-1 ]
  • [ 89362-14-1 ]
YieldReaction ConditionsOperation in experiment
90% In benzene for 96h; Ambient temperature;
  • 5
  • [ 33290-12-9 ]
  • [ 19131-99-8 ]
YieldReaction ConditionsOperation in experiment
91% With lithium aluminium tetrahydride In tetrahydrofuran at 25℃; for 7h;
61% With lithium aluminium tetrahydride In diethyl ether for 1h; Heating;
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating; Yield given;
  • 6
  • [ 19131-99-8 ]
  • [ 98-09-9 ]
  • [ 134295-63-9 ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine In dichloromethane for 0.333333h; Heating;
  • 7
  • [ 14185-42-3 ]
  • [ 19131-99-8 ]
YieldReaction ConditionsOperation in experiment
75% With lithium aluminium tetrahydride In tetrahydrofuran for 1h; Heating;
With lithium aluminium tetrahydride In tetrahydrofuran Heating;
  • 8
  • [ 19131-99-8 ]
  • [ 79-04-9 ]
  • [ 155795-38-3 ]
YieldReaction ConditionsOperation in experiment
94.5% In benzene at 15 - 20℃; for 0.5h;
  • 9
  • [ 19131-99-8 ]
  • [ 106967-42-4 ]
  • (-)-4-brom-2,6-bis(N-methyl-N-1'-phenylethylaminomethyl)pyridin [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 24h; Heating;
  • 10
  • [ 19131-99-8 ]
  • [ 167933-96-2 ]
YieldReaction ConditionsOperation in experiment
91% With tert.-butylnitrite In tetrahydrofuran for 3h; Heating;
  • 11
  • [ 173278-25-6 ]
  • [ 19131-99-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In 1,4-dioxane at 25℃; for 1h;
  • 12
  • [ 10557-01-4 ]
  • [ 19131-99-8 ]
YieldReaction ConditionsOperation in experiment
95% With pyrrolidine; (S,S)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium difluoride; phenylsilane In tetrahydrofuran; methanol at 35℃; for 12h;
  • 13
  • [ 19131-99-8 ]
  • [ 1218-34-4 ]
  • (S)-2-Acetylamino-3-(1H-indol-3-yl)-N-methyl-N-((S)-1-phenyl-ethyl)-propionamide [ No CAS ]
  • 14
  • [ 19131-99-8 ]
  • [ 57072-87-4 ]
  • 2-Diazo-N-methyl-N-((S)-1-phenyl-ethyl)-malonamic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With triethylamine In dichloromethane
  • 15
  • [ 19131-99-8 ]
  • [ 107-86-8 ]
  • (S)-N-methyl-N-(3-methylbuta-1,3-dienyl)-1-phenylethylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With potassium carbonate In benzene at 20℃; for 24h;
  • 16
  • [ 19131-99-8 ]
  • [ 37091-73-9 ]
  • N-[(S)-1-phenylethyl]-N,N',N''-trimethyl-N',N''-ethyleneguanidinium chloride [ No CAS ]
  • 17
  • [ 19131-99-8 ]
  • 1,2-bis[(S)-1-phenylethyl]-2-chloroimidazolinium chloride [ No CAS ]
  • 1,3-bis[(S)-1-phenylethyl]-2-[(S)-1-phenylethylimino]imidazolidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With triethylamine In dichloromethane at 20℃;
  • 18
  • [ 19131-99-8 ]
  • [ 192124-66-6 ]
  • [3-(<i>tert</i>-butoxycarbonyl-[methyl-(1-phenyl-ethyl)-carbamoyl]-methyl}-amino)-propyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃;
  • 19
  • [ 19131-99-8 ]
  • [ 42882-26-8 ]
YieldReaction ConditionsOperation in experiment
99 % Chromat. With 2,4-dimethyl-3-pentanol In toluene at 110℃; for 1h;
With [CpIrI2]2 at 80℃; for 5h;
With hydrogen; nickel In toluene at 70℃; for 48h; Autoclave;
With [Ir(η5-C5Me5)(C6H4-2-C3H5N2)(NCCH3)](PF6) In chlorobenzene at 100℃; for 0.666667h; Inert atmosphere;
With Tridecane; pentamethylcyclopentadienyliridium (III)Iodide Dimer; potassium iodide In toluene at 80℃; for 1h;
With μ-diiodo-di((η5-pentamethylcyclopentadienyl)(iodo)iridium) In toluene at 80℃;

  • 20
  • [ 2627-86-3 ]
  • [ 74-88-4 ]
  • [ 19131-99-8 ]
YieldReaction ConditionsOperation in experiment
87% Stage #1: (<i>S</i>)-1-phenyl-ethylamine With sodium hydride In tetrahydrofuran Stage #2: methyl iodide In tetrahydrofuran for 8h;
  • 21
  • [ 19131-99-8 ]
  • [ 623-43-8 ]
  • (R)-3-[Methyl-((S)-1-phenyl-ethyl)-amino]-butyric acid methyl ester [ No CAS ]
  • (S)-3-[Methyl-((S)-1-phenyl-ethyl)-amino]-butyric acid methyl ester [ No CAS ]
  • <i>N</i>-methyl-3-[methyl-(1-phenyl-ethyl)-amino]-<i>N</i>-(1-phenyl-ethyl)-butyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 73% 2: 4% 3: 23% With n-butyllithium In tetrahydrofuran at -70℃;
  • 22
  • [ 19131-99-8 ]
  • [ 73545-15-0 ]
  • isobutyl (3R)-3-{methyl[(1S)-1-phenylethyl]amino}butanoate [ No CAS ]
  • [ 161011-01-4 ]
  • <i>N</i>-methyl-3-[methyl-(1-phenyl-ethyl)-amino]-<i>N</i>-(1-phenyl-ethyl)-butyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 80% 2: 5% 3: 7% With n-butyllithium In tetrahydrofuran at -70℃; for 0.5h;
  • 23
  • [ 19131-99-8 ]
  • neo-pentyl crotonate [ No CAS ]
  • (R)-3-[Methyl-((S)-1-phenyl-ethyl)-amino]-butyric acid 2,2-dimethyl-propyl ester [ No CAS ]
  • (S)-3-[Methyl-((S)-1-phenyl-ethyl)-amino]-butyric acid 2,2-dimethyl-propyl ester [ No CAS ]
  • <i>N</i>-methyl-3-[methyl-(1-phenyl-ethyl)-amino]-<i>N</i>-(1-phenyl-ethyl)-butyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 49% 2: 12% 3: 39% With n-butyllithium In tetrahydrofuran at -70℃;
  • 24
  • [ 19131-99-8 ]
  • [ 623-43-8 ]
  • [ 106-95-6 ]
  • [ 644984-50-9 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: N-methyl-N-[(S)-1-phenylethyl]amine With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: crotonic acid methyl ester In tetrahydrofuran at -78℃; Stage #3: allyl bromide In tetrahydrofuran at 0℃;
  • 25
  • [ 19131-99-8 ]
  • [ 623-70-1 ]
  • (R)-3-[Methyl-((S)-1-phenyl-ethyl)-amino]-butyric acid ethyl ester [ No CAS ]
  • (S)-3-[Methyl-((S)-1-phenyl-ethyl)-amino]-butyric acid ethyl ester [ No CAS ]
  • <i>N</i>-methyl-3-[methyl-(1-phenyl-ethyl)-amino]-<i>N</i>-(1-phenyl-ethyl)-butyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 84% 2: 5% 3: 11% With n-butyllithium In tetrahydrofuran at -70℃;
  • 26
  • [ 1641-40-3 ]
  • [ 19131-99-8 ]
  • Benzo[1,3,2]dioxaphosphol-2-yl-methyl-((S)-1-phenyl-ethyl)-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In diethyl ether at 0 - 20℃;
  • 27
  • [ 10557-01-4 ]
  • [ 19131-99-8 ]
  • [ 5933-40-4 ]
YieldReaction ConditionsOperation in experiment
With formic acid; bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; triethylamine; (R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine; at 40℃; for 2h;Inert atmosphere; To a nitrogen-purged flask was added (E)-N-(alpha-methylbenzylidene)methylamine (135 mg, 1 mmol), [IrCp*Cl2]2 (4 mg, 0.005 mmol), (R,R)-TsDPEN (4 mg, 0.01 mmol). To this mixture was then added formic acid/triethylamine 5:2 (1 mL). The reaction mixture was stirred under nitrogen at 40 C for 2 hours. Following this the reaction solution was filtered through silica (1:1 EtOAc/petroleum ether40-60) and the resulting solution dried by rotary evaporation to leave the crude product as a paleyellow oil. The crude was analysed by chiral GC to confirm formation of the product and to determineconversion and enantiomeric excess. GC method: CP-Chirasil-Dex-CB, 25 m 0.25 mm, 0.25 mum. H2 7.5 psi, injector 250 C, FID 250 C,oven: 80 C hold 1 min, 100 C/min to 100 C, 13 min hold, 100 C/min to 200 C, 5 min hold. (R)-amine 16.6 min. (S)-amine 17.1 min.
  • 28
  • [ 19131-99-8 ]
  • [ 66-77-3 ]
  • [ 135-19-3 ]
  • 1-{(S)-[methyl-((S)-1-phenyl-ethyl)-amino]-naphthalen-1-yl-methyl}-naphthalen-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% at 85℃; for 72h;
51% at 85℃; for 72h; 1 1-Naphthaldehyde (2.7 mL, 20 mmol), (S)-(-)-N, α-dimethylbenzylamine (2.60 g, 19 mmol) and 2-naphthol (2.43 g, 16 mmol) are charged into a 25 mL flask with a magnetic stirring bar. The mixture is heated to 85°C and stirred for 72 h. After the system is cooled to RT, MeOH (5 mL) is added and the precipitated product is collected by filtration, washed with OH (5 mL) and dried to afford 1-{(S)-[methyl-((S)-1-phenyl-ethyl)-amino]-naphthalen- 1-yl-methyl}-naphthalen-2-ol as white crystals (about 51% yield) : 1H NMR (500 MHz, CDCl3) õ 14. 01 (br s, 1H), 7.77-7. 02 (m, 18H), 6.45 (s, 1H), 4.40 (brs, 1H), 1.95 (s, 3H), 1.65 (br s, 3H); MS (Ei) m/z (rel intensity) 418 (M +1), 283, 141, 136; HRMS (EI) Calcd for C3oH28NO (M++1) : 418.2171, found 418. 2135.
  • 29
  • [ 142653-49-4 ]
  • [ 19131-99-8 ]
  • 2-(5,7-dimethyl-2-phenyl-pyrazolo[1,5-<i>a</i>]pyrimidin-3-yl)-<i>N</i>-methyl-<i>N</i>-(1-phenyl-ethyl)-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% Stage #1: (5,7-dimethyl-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)acetic acid With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at -10℃; for 1h; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In tetrahydrofuran at 20℃; for 5h;
  • 30
  • [ 840505-84-2 ]
  • [ 19131-99-8 ]
  • (1S,7S)-4-(N-methyl-N-(S)-1-phenylethylamino)-9,9-dimethyl-2,2,6,6-tetra(3,5-dimethylphenyl)-3,5,8,10-tetraoxa-4-phosphabicyclo[5.3.0]decane [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% With triethylamine In toluene
  • 31
  • [ 19131-99-8 ]
  • [ 185683-00-5 ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: N-methyl-N-[(S)-1-phenylethyl]amine With trichlorophosphate In diethyl ether at 0 - 20℃; Stage #2: for 20h; Heating;
  • 32
  • [ 19131-99-8 ]
  • C9H12Cl2NP [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; phosphorus trichloride In toluene at 70℃; for 6h;
With triethylamine; phosphorus trichloride In toluene at 70℃; for 6h;
With triethylamine; phosphorus trichloride In toluene at 70℃; for 6h;
  • 33
  • [ 19131-99-8 ]
  • (S)-3-Chloro-2-((S)-1-phenyl-ethyl)-1,2,5,6,7,7a-hexahydro-pyrrolo[1,2-c]imidazol-4-ylium; chloride [ No CAS ]
  • (5S)-3-[(S)-1-phenylethyl]-2-[(S)-1-phenylethylimino]-1,3-diazabicyclo[3.3.0]octane [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With triethylamine In dichloromethane at 20℃; for 1h;
  • 34
  • [ 945483-25-0 ]
  • [ 19131-99-8 ]
  • [ 906750-09-2 ]
YieldReaction ConditionsOperation in experiment
91% With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2h;
  • 35
  • [ 945483-25-0 ]
  • [ 19131-99-8 ]
  • [ 945483-47-6 ]
YieldReaction ConditionsOperation in experiment
92% Stage #1: methyl (E)-(N-allyl-N-benzylamino)but-2-enoate; N-methyl-N-[(S)-1-phenylethyl]amine With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: With (+)-(2S,8aS)-(camphorylsulfonyl)oxaziridine In tetrahydrofuran; hexane at -78 - 20℃; for 12h; Further stages.;
  • 36
  • [ 19131-99-8 ]
  • trans-chrotonyl chloride [ No CAS ]
  • C13H17NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap In dichloromethane at 0 - 20℃;
  • 37
  • [ 19131-99-8 ]
  • [ 79218-15-8 ]
  • tert-butyl (3S,αS)-3-[N-methyl-N-(α-methylbenzyl)amino]butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: N-methyl-N-[(S)-1-phenylethyl]amine With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: tert-butyl (E)-crotonate In tetrahydrofuran at -78℃; for 2h; Further stages.;
  • 38
  • [ 19131-99-8 ]
  • [ 13600-42-5 ]
  • C16H13N3ClF3 [ No CAS ]
  • 39
  • [ 19131-99-8 ]
  • (5,7-dioxa-6-phospha-dibenzo[<i>a</i>,<i>c</i>]cyclohepten-6-yl)-methyl-(1-phenyl-ethyl)-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: PCl3; triethylamine / toluene / 6 h / 70 °C 2: triethylamine / tetrahydrofuran; toluene / -78 - 20 °C
Multi-step reaction with 2 steps 1: PCl3; Et3N / toluene / 6 h / 70 °C 2: Et3N / toluene; tetrahydrofuran / -78 - 25 °C
Multi-step reaction with 2 steps 1: Et3N; PCl3 / toluene / 6 h / 70 °C 2: Et3N / toluene; tetrahydrofuran / -78 - 20 °C
  • 40
  • [ 19131-99-8 ]
  • 2-(3-amino-propylamino)-<i>N</i>-methyl-<i>N</i>-(1-phenyl-ethyl)-acetamide; compound with trifluoro-acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: EDC; DMAP / CH2Cl2 / 20 °C 2: CH2Cl2 / 2 h / 20 °C
  • 41
  • [ 19131-99-8 ]
  • 3-[4-(N-benzyloxycarbonyl-N-methyl)aminophenyl]acrylic acid tert-butyl ester [ No CAS ]
  • (R)-3-[4-(N-benzyloxycarbonyl-N-methyl)aminophenyl]-3-[N-((S)-alpha-methylbenzyl)methylamino]-propionic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium In tetrahydrofuran; ethyl acetate R.24 (R)-3-[4-(N-Benzyloxycarbonyl-N-methyl)aminophenyl]-3-[N-((S)-alpha-methylbenzyl)methylamino]propionic acid tert-butyl ester Reference Example 24 (R)-3-[4-(N-Benzyloxycarbonyl-N-methyl)aminophenyl]-3-[N-((S)-alpha-methylbenzyl)methylamino]propionic acid tert-butyl ester A solution of (S)-N-(alpha-methylbenzyl)methylamine (3.8 g) in tetrahydrofuran (60 ml) was cooled to less than -70° C. under a blanket of nitrogen, then treated with a solution of butyllithium in hexanes (11.3 ml, 2.5 M), keeping the temperature at or below -60° C. Ten minutes after the addition was complete a solution of 3-[4-(N-benzyloxycarbonyl-N-methyl)aminophenyl]acrylic acid tert-butyl ester (4.7 g, Reference Example 25) in tetrahydrofuran (40 ml) was added slowly over 20 minutes. After a further 20 minutes at below -70° C. the cold reaction mixture was poured directly into a mixture of ethyl acetate and brine, then the layers were separated and the organic phase was dried over magnesium sulphate and then evaporated. The residue was subjected to flash chromatography on silica eluding with a mixture of ethyl acetate and cyclohexane mixture (3:7, v/v) to give the title compound (5.5 g) as a colourless oil.
YieldReaction ConditionsOperation in experiment
With cesium iodide;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In tetrahydrofuran; chloroform; at 40℃;Product distribution / selectivity; A solution of pentamethylcyclopentadienyliridiumON) chloride dimer was prepared by dissolving the dimer (16.Q mg 96%, 15.9 mg, 0.020 mmol) in chloroform (0.5 ml) resulting in a dark orange solution (Iridium Catalyst solution).A solution of iodine was prepared by dissolving the solid (17.1 mg 99%, 16.9mg, 0.067mmol) in tetrahydrofuran (0.5 ml) this resulted in a dark brown solution (Iodine solution) (75 mul of this solution corresponds to 0.01 mmol iodine).A small quantity of the potassium iodide used for these reactions was placed in the oven at 17O0C and dried to constant weight. A second sample of the potassium iodide was ground to a fine powder then placed in the oven and dried to constant weight (-1% weight loss).Seven G. C. vials were set up containing a magnetic flea and (R)-N-Methyl-alpha- methylbenzylamine (13.8 mg Theta8%, 13.5 mg, 0.10 mmol) the following material was added to each vial:-1. Caesium iodide (26.0 mg 99.9%, 26.0 mg, 0.10 mmol), tetrahydrofuran (75 mul) and the iridium catalyst solution (25 mul).2. Potassium iodide (15. 1 mg 99%, 14.9 mg, 0.10 mmol), iodine solution C75 mul) and the iridium catalyst solution (25 mul).3. Iodine solution (75 mul) and the iridium catalyst solution (25 mul).4. Potassium bromide (1 2.0 mg 99%, 11.9 mg, 0.09 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).5. Potassium iodide dried powder (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).6. Potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution <75 mul) and the iridium catalyst solution (25 mul).7. Dried potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine sol ution (75 mul) and the iridium catalyst solution (25 mul). EPO <DP n="15"/>Each vial was sealed and placed in a stem block at 4O0C, samples were taken after stirring overnight by quenching 20 mul of the reaction solution into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated, dried using sodium sulphate and analysed by chiral and achiral G. C.AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column ( 30m, 320mum, 0.25mum), 70 0C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylamine = 6.8 minsGas Chromatography (for ee)Varian Chirasil -Dex-CB column (25 m, 250 m, 0.25 m), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins EPO <DP n="16"/>
mu-diiodo-di((eta5-pentamethylcyclopentadienyl)(iodo)iridium); In toluene; at 80℃; for 13.3333 - 16h;Product distribution / selectivity; To a 5 ml single-neck round-bottom flask is added the chiral amine (2 mmol), pentamethylcyclopentadienyl iridium (111) iodide dimer* (0.02 mmol) and toluene (4 ml). A condenser is attached to the flask and it is placed into an oil bath at 8O0C and agitated using a magnetic stirrer.Samples are taken at regular intervals and analysed for conversion and enantiomeric excess.* An alternative procedure involves the addition of pentamethylcyclopentadienyl iridium (III) chloride dimer (0.02 mmol) and potassium iodide (2 mmol).
With potassium iodide;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 80℃; for 0 - 20.75h;Product distribution / selectivity; Air purgePentamethylcyclopentadienyliridiumOII) chloride dimer (16.6 mg 96%, 15.9 mg, 0.02 mmol), (R)-N-methyl-alpha-methylbenzylamine (275.9 mg 98%, 270.4- mg, 2.00 mmol) and potassium iodide (335.4 mg 99%, 332.0 mg, 2.00 mmol) were charged to a 5 ml round-bottom flask. Toluene (4 ml) was added and a water condenser was attached to the flask which was then placed in a oil bath at 8O0C. An air purge was passed through the reaction solution (10 ml/min) and a timer was started. The reaction solution immediately turned to a dark red/brown that faded over 60 mins to a dark orange solution. The colour of the solution gradually faded and was a clear orange solution after stirring overnight.In order to replace solvent lost due to the purge, toluene (2 ml) was added after five hours.Samples were taken at regular intervals by removing 100-200 mul and quenching into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated and dried using sodium sulphate. The resulting organic layer was analysed by chiral and achiral g.c.; AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column (30m, 320mum, O.25mum), 700C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylamine = 6.8 mins EPO <DP n="18"/>Gas Chromatography (for ee)N-methyl-alpha-methylbenzylamineVarian Chirasil -Dex-CB column (25 m, 250 mum, 0.25 mum), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins; Racemisation of (R)-N-Methyl-alpha-methylbenzylamine in toluene at 800C using [lrCp*CI?]? + Kl + Air purge.
With iodine; potassium iodide;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In tetrahydrofuran; chloroform; at 40℃;Product distribution / selectivity; A solution of pentamethylcyclopentadienyliridiumON) chloride dimer was prepared by dissolving the dimer (16.Q mg 96%, 15.9 mg, 0.020 mmol) in chloroform (0.5 ml) resulting in a dark orange solution (Iridium Catalyst solution).A solution of iodine was prepared by dissolving the solid (17.1 mg 99%, 16.9mg, 0.067mmol) in tetrahydrofuran (0.5 ml) this resulted in a dark brown solution (Iodine solution) (75 mul of this solution corresponds to 0.01 mmol iodine).A small quantity of the potassium iodide used for these reactions was placed in the oven at 17O0C and dried to constant weight. A second sample of the potassium iodide was ground to a fine powder then placed in the oven and dried to constant weight (-1% weight loss).Seven G. C. vials were set up containing a magnetic flea and (R)-N-Methyl-alpha- methylbenzylamine (13.8 mg Theta8%, 13.5 mg, 0.10 mmol) the following material was added to each vial:-1. Caesium iodide (26.0 mg 99.9%, 26.0 mg, 0.10 mmol), tetrahydrofuran (75 mul) and the iridium catalyst solution (25 mul).2. Potassium iodide (15. 1 mg 99%, 14.9 mg, 0.10 mmol), iodine solution C75 mul) and the iridium catalyst solution (25 mul).3. Iodine solution (75 mul) and the iridium catalyst solution (25 mul).4. Potassium bromide (1 2.0 mg 99%, 11.9 mg, 0.09 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).5. Potassium iodide dried powder (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).6. Potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution <75 mul) and the iridium catalyst solution (25 mul).7. Dried potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine sol ution (75 mul) and the iridium catalyst solution (25 mul). EPO <DP n="15"/>Each vial was sealed and placed in a stem block at 4O0C, samples were taken after stirring overnight by quenching 20 mul of the reaction solution into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated, dried using sodium sulphate and analysed by chiral and achiral G. C.AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column ( 30m, 320mum, 0.25mum), 70 0C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylamine = 6.8 minsGas Chromatography (for ee)Varian Chirasil -Dex-CB column (25 m, 250 m, 0.25 m), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins EPO <DP n="16"/>
With decane; potassium iodide;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 80℃; for 0 - 24h;Product distribution / selectivity; Pentarnethylcyclopentadienyliridium(lll) chloride dimer (16.6 mg 96%, 15.9 mg, 0.02 mmol), (R)-N-methyl-alpha-methylbenzylamine (275.9 mg 98%, 270.4 mg, 2.00 mmol), potassium iodide (335.4 mg 99%, 332.0 mg, 2.00 mmol) and n-decane (143.4 mg 99%, 142.0 mg, 1.00 mmol) were charged to a 5 ml round-bottom flask. Toluene was degassed by sparging through the solvent with nitrogen for 30 minutes then 4 ml was added and a water condenser was attached to the flask which was then placed in a oil bath at 800C and a timer was started. A nitrogen purge was passed through the reaction solution (10 ml/min). The reaction solution immediately turned to a dark red/brown that faded over 60 mins to a dark orange solution. The colour of the solution gradually faded and was a clear orange solution after stirring overnight. In order to replace solvent lost due to the purge toluene (2 ml) was added after 325 minutes.Samples were taken at regular intervals by removing 100-200 mul and quenching into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated and dried using sodium sulphate. The resulting organic layer was analysed by chiral and achiral g.c.AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column (30m, 320mum, O.25mum), 700C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylamine = 6.8 mins EPO <DP n="18"/>Gas Chromatography (for ee)N-methyl-alpha-methylbenzylamineVarian Chirasil -Dex-CB column (25 m, 250 mum, 0.25 mum), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins; EPO <DP n="19"/>Racemisation of (R)-N-Methyl-alpha-methylbenzylannine in toluene at 8O0C us ing [lrCp*CI?1, + Kl + Nitrogen purge.
With biphenyl; potassium iodide;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 80℃; for 0 - 22h;Product distribution / selectivity; Pentamethylcyclopentadienyliridium(lll) chloride dimer (16.6 mg 96%, 15.9 mg, 0.02 mmol), (R)-N-methyl-alpha-methylbenzylamine (275.9 mg 98%, 270.4- mg, 2.00 mmol), potassium iodide (335.4 mg 99%, 332.0 mg, 2.00 mmol) and biphenyl (155.0 mg 99.5%, 154.2 mg, 1.00 mmol) were charged to a 5 ml round-bottom flask. Toluene (4 ml) was EPO <DP n="17"/>added, a water condenser was attached to the flask, the flask was then placed in an oil bath at 8O0C and a timer was started. The reaction solution immediately turned to a dark red/brown that faded over 60 mins to a dark orange solution. The colour of the solution gradually faded and was a clear orange solution after stirring overnight.Samples were taken at regular intervals by removing 100-200 mul and quenching into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated and dried using sodium sulphate. The resulting organic layer was analysed by chiral and achiral g.c.; AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column (30m, 320mum, O.25mum), 700C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylamine = 6.8 mins EPO <DP n="18"/>Gas Chromatography (for ee)N-methyl-alpha-methylbenzylamineVarian Chirasil -Dex-CB column (25 m, 250 mum, 0.25 mum), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins; Racemisation of (R)-N-Methyl-alpha-methylbenzylamine in toluene at 8O0C using [lrCp*CI?]? + Kl (without a purge).
With Tridecane; potassium iodide;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 80℃; for 0 - 21h;Product distribution / selectivity; PentamethylcyclopentadienyliridiumOII) chloride dimer (16.6 mg 96%, 15.9 mg, 0.02 mmol), (R)-N-methyl-alpha-rnethylbenzylamine (275.9 mg 98%, 270.4 rng, 2.00 mmol), potassium iodide (335.4 mg 99%, 332.0 mg, 2.00 mmol) and tridecane (186.2 mg 99%, 184.4 mg, 1.00 mmol) were charged to a 5 ml round-bottom flask. Toluene (4 ml) was added, a water condenser was attached to the flask, the flask was then placed in an oil bath at 8O0C, and a timer was started. The reaction solution immediately turned to a dark red/brown that faded over 6O mins to a dark orange solution. The colou r of the solution gradually faded and was a clear orange solution after stirring overnight.Samples were taken at regular intervals by removing 100-200 mul and quenching into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated and dried using sodium sulphate. The resulting organic layer was analysed by chiral and achiral g.c.AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column (30m, 320mum, 0.25mum> , 70 0C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylam ne = 6.8 mins EPO <DP n="20"/>Gas Chromatography (for ee)N-methyl-alpha-methylbenzylamineVarian Chirasil -Dex-CB column (25 m, 250 mum, 0.25 mum), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 minsRacemisation of (S)-N-Methyl-alpha-methylbenzylamine in toluene at 80C using flrCp*CI?1? + Kl (No purge used)
With iodine;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In tetrahydrofuran; chloroform; at 40℃;Product distribution / selectivity; A solution of pentamethylcyclopentadienyliridiumON) chloride dimer was prepared by dissolving the dimer (16.Q mg 96%, 15.9 mg, 0.020 mmol) in chloroform (0.5 ml) resulting in a dark orange solution (Iridium Catalyst solution).A solution of iodine was prepared by dissolving the solid (17.1 mg 99%, 16.9mg, 0.067mmol) in tetrahydrofuran (0.5 ml) this resulted in a dark brown solution (Iodine solution) (75 mul of this solution corresponds to 0.01 mmol iodine).A small quantity of the potassium iodide used for these reactions was placed in the oven at 17O0C and dried to constant weight. A second sample of the potassium iodide was ground to a fine powder then placed in the oven and dried to constant weight (-1% weight loss).Seven G. C. vials were set up containing a magnetic flea and (R)-N-Methyl-alpha- methylbenzylamine (13.8 mg Theta8%, 13.5 mg, 0.10 mmol) the following material was added to each vial:-1. Caesium iodide (26.0 mg 99.9%, 26.0 mg, 0.10 mmol), tetrahydrofuran (75 mul) and the iridium catalyst solution (25 mul).2. Potassium iodide (15. 1 mg 99%, 14.9 mg, 0.10 mmol), iodine solution C75 mul) and the iridium catalyst solution (25 mul).3. Iodine solution (75 mul) and the iridium catalyst solution (25 mul).4. Potassium bromide (1 2.0 mg 99%, 11.9 mg, 0.09 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).5. Potassium iodide dried powder (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).6. Potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution <75 mul) and the iridium catalyst solution (25 mul).7. Dried potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine sol ution (75 mul) and the iridium catalyst solution (25 mul). EPO <DP n="15"/>Each vial was sealed and placed in a stem block at 4O0C, samples were taken after stirring overnight by quenching 20 mul of the reaction solution into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated, dried using sodium sulphate and analysed by chiral and achiral G. C.AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column ( 30m, 320mum, 0.25mum), 70 0C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylamine = 6.8 minsGas Chromatography (for ee)Varian Chirasil -Dex-CB column (25 m, 250 m, 0.25 m), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins EPO <DP n="16"/>
With iodine; potassium bromide;bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In tetrahydrofuran; chloroform; at 40℃;Product distribution / selectivity; A solution of pentamethylcyclopentadienyliridiumON) chloride dimer was prepared by dissolving the dimer (16.Q mg 96%, 15.9 mg, 0.020 mmol) in chloroform (0.5 ml) resulting in a dark orange solution (Iridium Catalyst solution).A solution of iodine was prepared by dissolving the solid (17.1 mg 99%, 16.9mg, 0.067mmol) in tetrahydrofuran (0.5 ml) this resulted in a dark brown solution (Iodine solution) (75 mul of this solution corresponds to 0.01 mmol iodine).A small quantity of the potassium iodide used for these reactions was placed in the oven at 17O0C and dried to constant weight. A second sample of the potassium iodide was ground to a fine powder then placed in the oven and dried to constant weight (-1% weight loss).Seven G. C. vials were set up containing a magnetic flea and (R)-N-Methyl-alpha- methylbenzylamine (13.8 mg Theta8%, 13.5 mg, 0.10 mmol) the following material was added to each vial:-1. Caesium iodide (26.0 mg 99.9%, 26.0 mg, 0.10 mmol), tetrahydrofuran (75 mul) and the iridium catalyst solution (25 mul).2. Potassium iodide (15. 1 mg 99%, 14.9 mg, 0.10 mmol), iodine solution C75 mul) and the iridium catalyst solution (25 mul).3. Iodine solution (75 mul) and the iridium catalyst solution (25 mul).4. Potassium bromide (1 2.0 mg 99%, 11.9 mg, 0.09 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).5. Potassium iodide dried powder (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution (75 mul) and the iridium catalyst solution (25 mul).6. Potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine solution <75 mul) and the iridium catalyst solution (25 mul).7. Dried potassium iodide (16.8 mg 99%, 16.6 mg, 0.10 mmol), iodine sol ution (75 mul) and the iridium catalyst solution (25 mul). EPO <DP n="15"/>Each vial was sealed and placed in a stem block at 4O0C, samples were taken after stirring overnight by quenching 20 mul of the reaction solution into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated, dried using sodium sulphate and analysed by chiral and achiral G. C.AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column ( 30m, 320mum, 0.25mum), 70 0C isothermal for 30mins, 15.0 psi.N-methyl-alpha-methylbenzylamine = 6.8 minsGas Chromatography (for ee)Varian Chirasil -Dex-CB column (25 m, 250 m, 0.25 m), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins EPO <DP n="16"/>
With Tridecane;mu-diiodo-di((eta5-pentamethylcyclopentadienyl)(iodo)iridium); In toluene; at 80℃; for 0 - 22.0333h;Product distribution / selectivity; Pentamethylcyclopentadienyliridium(lll) iodide dimer (24.2 mg 96%, 23.25 mg, 0.02 mmol), (S)-N-methyl-alpha-methylbenzylamine (275.9 mg 98%, 270.4 mg, 2.00 mmol) and tridecane (186.2 mg 99%, 184.4 mg, 1.00 mmol) were charged to a 5 ml round- bottom flask. Toluene (4 ml) was added and a water condenser was attached to the flask which was then placed in a oil bath at 8O0C and a timer was started. The reaction solution immediately turned. to a dark red/brown that faded over 60 mins to a dark orange solution. The colour of the solution gradually faded and was a clear orange solution after stirring overnight.Samples were taken at regular intervals by removing 100-200 mul and quenching into dichloromethane (2 ml) and 2.5 M sodium hydroxide (2 ml), the organic layer was separated and dried using sodium sulphate. The resulting organic layer was analysed by EPO <DP n="21"/>chiral and achiral g.c.AnalysisGas Chromatography (for conversion)HP-5 5% Methyl Phenyl Siloxane capillary column (30m, 320mum, 0.25mum), 70 0C isothermal for 30mins, 15.0 psi.N-methyl-alpha-rnethylbenzylamine = 6.8 minsGas Chromatography (for ee)N-methyl-alpha-rnethylbenzylamineVarian Chirasil -Dex-CB column (25 m, 250 mum, 0.25 mum), 1000C isothermal for 60 mins. N. B. One drop of trifluoroacetic anhydride was added to each sample vial prior to injection.R enantiomer N-methyl-alpha-methylbenzylamine = 58.4 mins S enantiomer N-methyl-alpha-methylbenzylamine = 54.8 mins

  • 43
  • [ 19131-99-8 ]
  • [ 73545-15-0 ]
  • 3-(N-methyl-N-(S)-1'-phenylethylamino)butyric acid, 2-methylpropyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
290 g (65%) With hydrogenchloride; sodium hydroxide In tetrahydrofuran; methanol; dichloromethane; water; ethyl acetate a.b.2 EXAMPLES OF COMPOUNDS FROM CHART E-CHART EX1 Step 2 of CHART EX1. Synthesis of 3-(N-Methyl-N-(S)-1'-phenylethylamino)butyric acid, 2-methylpropyl ester, EX12. Add N-methyl-N-(S)-1-phenylethylamine (EX11b, 390.0 g, 2.88 mol, 1.1 eq) and THF (14 L) to a 22 L flask. Cool this solution to -5° C. and add n-buLi (1.80 L, 2,88 mol,) over a period of 30 min. maintaining the internal reaction temperature below 0° C. The solution is stirred at 0° C. for 30 min. and then cooled to -78° C. A pre-cooled, to -40° C., solution of isobutyl crotonate (372 g) in THF (3.0 L) is added at a rate such that the internal reaction temperature does not exceed -70° C. After the addition is complete, the reaction is stirred at -75° C. for 30 min. The reaction is quenched with saturated NH4 Cl until the pH is between about 9 to 11. The organic phase is separated and the solvent is removed in vacuo. The product is redissolved in EtOAc (1.5 L) and the resulting solution is filtered. The EtOAc is distilled off and MeOH (1.0 L) and 37% HCl (210 mL) are added. MTBE (5 L) is added to crystallize the amine hydrochloride salt of the 2-methylpropyl ester of 3-(N-methyl-N-(S)-l'-phenylethylamino)butyric acid. The crystalline amine hydrochloride salt is dissolved in CH2 Cl2 (2.5 L) and water (1.0 L) is added. A 10% NaOH solution is used to adjust the pH to between about 9 to 11. The organic layer is separated and the solvent is removed in vacuo to yield 290 g (65%) of 3-(N-methyl-N-(S)-1'-phenylethylamino)butyric acid, 2-methylpropyl ester. 13 C-NMR (CDCl3, ppm δ) 14.70, 19.39, 21.97, 27.95, 32.31, 39.25, 51.43, 62.36, 70.70, 126.91, 127.40, 128.47, 146.45, 173.06.
  • 44
  • [ 19131-99-8 ]
  • [ 887703-77-7 ]
  • C23H24FN3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 1-(4-fluorophenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid With 1-hydroxybenzotriazol-hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 25℃; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In dichloromethane at 25℃; Further stages.;
  • 45
  • [ 19131-99-8 ]
  • [ 62965-35-9 ]
  • [ 23165-29-9 ]
  • [ 1032509-37-7 ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: N-methyl-N-[(S)-1-phenylethyl]amine; N-tert-butyloxycarbonyl-L-tert-leucine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Stage #2: With hydrogenchloride In 1,4-dioxane at 20℃; Stage #3: 3,5-bistrifluoromethylphenylisothiocyanate With triethylamine In dichloromethane at 20℃; Further stages.;
  • 46
  • [ 19131-99-8 ]
  • [(R)-1,1'-binaphthyl-2,2'-diyl]chlorophosphite [ No CAS ]
  • C29H24NO2P [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% Stage #1: N-methyl-N-[(S)-1-phenylethyl]amine With n-butyllithium In tetrahydrofuran; hexane at -78 - -30℃; Inert atmosphere; Stage #2: [(R)-1,1'-binaphthyl-2,2'-diyl]chlorophosphite In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;
  • 47
  • [ 19131-99-8 ]
  • [ 32315-10-9 ]
  • [ 74-89-5 ]
  • [ 1042947-18-1 ]
YieldReaction ConditionsOperation in experiment
67% Stage #1: N-methyl-N-[(S)-1-phenylethyl]amine; bis(trichloromethyl) carbonate With triethylamine In dichloromethane at 0℃; for 1h; Inert atmosphere; Stage #2: methylamine In tetrahydrofuran; dichloromethane at 0 - 20℃; Inert atmosphere;
  • 48
  • [ 19131-99-8 ]
  • [ 103-72-0 ]
  • [ 1162043-73-3 ]
YieldReaction ConditionsOperation in experiment
97% In acetonitrile at 20℃; Inert atmosphere;
  • 49
  • [ 19131-99-8 ]
  • [ 375-16-6 ]
  • [ 1206684-19-6 ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine In diethyl ether at -10 - 20℃; Inert atmosphere;
  • 50
  • [ 19131-99-8 ]
  • [ 1225280-50-1 ]
  • [ 1225278-97-6 ]
YieldReaction ConditionsOperation in experiment
69% Stage #1: N-methyl-N-[(S)-1-phenylethyl]amine; 3-(quinoxalin-6-yl)benzaldehyde With trimethyl orthoformate In dichloromethane at 20℃; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane for 0.5h; 3 EXAMPLE 3; N-Methyl-TV-f^-l-phenylethyll-TV-fS-fquinoxalin--vDbenzyllamine(S)-N-Methyl-N-(l-phenylethyl)amine (32 mg, 0.24 mmol) was added to a solution/suspension of Intermediate I (50 mg, 0.21 mmol) in DCM (3 mL) at r.t. Triniethyl orthoformate (0.2 mL) was added, and the mixture stirred for 30 minutes. Sodium triacetoxyborohydride (54 mg, 0.26 mmol) was added and the mixture stirred for 0.5 h. The mixture was quenched with saturated ammonium chloride solution (0.1 mL) and concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (45 mg, 69%) as a beige solid. δH (CDCl3) 8.88 (d, IH), 8.81 (d, IH), 8.33 (d, IH), 8.18 (d, IH), 8.07 (dd, IH), 7.73 (s, IH), 7.63 (d, IH), 7.32-7.50 (m, 6H), 7.22-7.30 (m, IH), 3.61-3.79 (m, 2H), 3.41 (d, IH), 2.20 (s, 3H), 1.46 (d, 3H). LCMS (ES+) 354 (M+H)+, RT 4.58 minutes.
  • 51
  • [ 19131-99-8 ]
  • [ 203869-80-1 ]
  • [ 1229277-61-5 ]
  • [ 1229277-63-7 ]
  • 52
  • [ 19131-99-8 ]
  • (cis)-2a,8b-bis(hydroxymethyl)-naphtho-9-oxa-bicyclo[2.2.1]hept-5-ene [ No CAS ]
  • [ 1333326-63-8 ]
YieldReaction ConditionsOperation in experiment
66% With bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran at 60℃; for 16h; Molecular sieve; Inert atmosphere; optical yield given as %de; enantioselective reaction;
  • 53
  • [ 19131-99-8 ]
  • (cis)-2a,6b-bis-hydroxymethyl-benzo-7-oxa-bicyclo[2.2.1]hept-5-ene [ No CAS ]
  • [ 1333326-61-6 ]
YieldReaction ConditionsOperation in experiment
48% With bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran at 60℃; for 16h; Molecular sieve; Inert atmosphere; optical yield given as %de; enantioselective reaction;
  • 54
  • [ 19131-99-8 ]
  • (cis)-2a,6b-bis-hydroxymethyl-benzo-7-oxa-bicyclo[2.2.1]hept-5-ene [ No CAS ]
  • [ 1333326-62-7 ]
YieldReaction ConditionsOperation in experiment
45% With bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran at 60℃; for 16h; Molecular sieve; Inert atmosphere; optical yield given as %de; enantioselective reaction;
  • 55
  • [ 75-44-5 ]
  • [ 19131-99-8 ]
  • [ 1392202-14-0 ]
YieldReaction ConditionsOperation in experiment
86% With triethylamine In dichloromethane; toluene at 20℃; Cooling with ice;
  • 56
  • [ 19131-99-8 ]
  • [ 1384850-39-8 ]
  • [ 1396753-54-0 ]
YieldReaction ConditionsOperation in experiment
76% With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 85℃; for 3h; 98.1 Step 1. (^-Methyl 3-(methyl(l-phenylethyl)amino)-2-oxo- l ,2-dihydroquinoxaline-6-To a solution of methyl 3-chloro-2-oxo- l ,2-dihydroquinoxaline-6-carboxylate (300 mg, 1.26 mmol) in DMSO (2 mL) was added DIEA (244 mg, 1.89 mmol), and (5)-N-methyl- l- phenylethanamine (204 mg, 1.51 mmol) with stirring for 3 h at 85°C in an oil bath. The reaction was then quenched by the addition of water (50 mL). The product was precipitated via the addition of water and collected by filtration to give (^-methyl 3-(methyl(l- phenylethyl)amino)-2-oxo-l ,2-dihydroquinoxaline-6-carboxylate as a gray solid (323 mg,76%).LC/MS (ES, m/z): [M+H]+ 338.1'H-NMR (300 MHz, CD3OD) δ 8.09 (d, / = 1.8 Hz, 1H), 7.79 - 7.82 (m, 1H), 7.33 - 7.43 (m, 5H), 7.19 - 7.29 (m, 1H), 6.66 - 6.73 (m, 1H), 3.92 (s, 3H), 2.94 (s, 3H), 1.66 (d, / = 6.9 Hz, 3H)
  • 57
  • [ 19131-99-8 ]
  • [ 1401298-94-9 ]
  • [ 1401298-98-3 ]
YieldReaction ConditionsOperation in experiment
In diethyl ether 2 General procedure for synthesis of salts 9 General procedure: To the solution of keto-acid 8 (100 mg, 0.36 mmol) in diethyl ether (5 mL) was added an equivalent of optically pure amine. Upon the addition, the precipitate formed immediately. The resulted suspension was filtered by suction to give the salt, which was then recrystallized from methanol. 3.2.2 (S)-(-)-N-Methyl-1-phenylethylamine salt of keto-acid 8 Mp 83-85 °C (Methanol). 1H NMR (400 MHz, CD3OD): δ 7.93 (d, J=8.5 Hz, 2H), 7.86 (d, J=8.5 Hz, 2H), 7.33 (m, 5H), 4.16 (q, J=6.9 Hz, 1H), 3.59 (m, 1H), 2.43 (s, 3H), 1.54 (d, J=6.9 Hz, 3H), 1.52 (m, 2H), 1.43 (m, 2H), 1.20 (m, 2H), 0.79 (d, J=6.6 Hz, 6H), 0.78 (d, J=6.5 Hz, 6H). 13C NMR (100 MHz, CD3OD): δ 206.8 (+), 173.9 (+), 143.3 (+), 140.0 (+), 138.1 (+), 130.6 (-), 130.5 (-), 130.4 (-), 128.8 (-), 128.6 (-), 60.5 (-), 43.5 (-), 43.3 (+), 31.6 (-), 27.4 (-), 23.3 (-), 23.1 (-), 19.4 (-). IR (KBr) νmax: 2954, 2777, 2378, 2129, 1672, 1552, 1382, 877, 795, 735, 700 cm-1. LRMS (ESI): 412 [M++1], 136, 105, 79. Anal. calcd for C26H37NO3: C, 75.87; H, 9.06; N, 3.40. Found: C, 76.00; H, 9.24; N, 3.50.
  • 58
  • [ 19131-99-8 ]
  • methyl 6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate [ No CAS ]
  • (S)-methyl 3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
15% In dimethyl sulfoxide at 130℃; for 0.5h; Microwave irradiation; 5; 6 (S)-methyl 3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate (S)-methyl 3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate A solution of methyl 6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate (2.0 g, 8.85 mmol) and (S)-N-methyl-1-phenylethanamine (2.39 g, 17.7 mmol; commercially available from Aldrich) in DMSO (20 mL) was heated at 130° C. in a microwave tube for 30 min. Water (100 mL) was added to the reaction mixture, and the product was extracted with EtOAc (3*100 mL). The combined EtOAc layers were concentrated and the residue was purified by flash chromatography (silica gel, 1% to 10% MeOH in CH2Cl2) to give the (S)-methyl 3-methyl-6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate (400 mg, 15% yield). LRMS [M+H]+: 325 m/z.
  • 59
  • [ 7197-01-5 ]
  • [ 19131-99-8 ]
  • (S)-N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% In 1-methyl-pyrrolidin-2-one at 200℃; for 1h; Sealed tube; Microwave irradiation; 4 Synthesis of (S)-N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (Compound 3) Example 4 Synthesis of (S)-N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (Compound 3) 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine (120 mg, 0.712 mmol; commercially available or prepared according to patent WO2006/039325A2), (S)-N-methyl-1-phenylethanamine (385 mg, 2.85 mmol) and anhydrous NMP (1 mL) were charged into a microwave tube equipped with a magnetic stirbar. After the vessel was sealed, the mixture was heated at 200° C. for 60 min using microwave irradiation. The reaction was purified by normal phase chromatography (10% CH2Cl2 in hexane then a gradient of 0% to 20% MeOH in CH2Cl2) and by reverse phase chromatography before being lyophilized to give the (S)-N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (Compound 3) as an off-white solid (69 mg; 36% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.01 (d, J=10.1 Hz, 1H), 7.25-7.39 (m, 6H), 5.71 (q, J=6.9 Hz, 1H), 2.84 (s, 3H), 2.54 (s, 3H), 1.58 (d, J=6.9 Hz, 3H). LRMS [M+H]+: 268 m/z.
  • 60
  • [ 19131-99-8 ]
  • [ 75680-93-2 ]
  • (S)-ethyl 6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% In acetonitrile for 36h; Reflux; 9 (S)-ethyl 6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate (S)-ethyl 6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate A solution of ethyl 6-chloro-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate (1.5 g, 6.6 mmol) and (S)-N-methyl-1-phenylethanamine (3.6 g, 26.4 mmol) in 20 mL of CH3CN was heated to reflux and stirred for 36 h. When cooled to room temperature, the reaction mixture was concentrated in vacuum, and the residue was purified by flash chromatography eluting with DCM/EA=5:1 to give product (S)-ethyl 6-(methyl(1-phenylethyl)amino)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate as a yellow oil (0.7 g, 32%). LRMS (M+H+) m/z: calcd 326.16; found 326. 1H NMR (300 MHz, CDCl3): 8.02-7.99 (d, J=9 Hz, 1H), 7.36-7.26 (m, 5H), 7.09-7.06 (d, J=9 Hz, 1H), 5.82-5.75 (q, 1H), 4.57-4.50 (q, 2H), 2.94 (s, 3H), 1.68-1.65 (d, 3H), 1.48-1.44 (t, 3H).
  • 61
  • [ 19131-99-8 ]
  • [ 6314-72-3 ]
  • (S)-N-methyl-N-(1-phenylethyl)-4-(N-phenylsulfamoyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: 4-(N-phenyl)sulfamoylbenzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 1h; Inert atmosphere; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In dichloromethane at 20℃; Inert atmosphere;
  • 62
  • [ 6907-71-7 ]
  • [ 19131-99-8 ]
  • [ 5933-40-4 ]
YieldReaction ConditionsOperation in experiment
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; (S)-4-tert-butyl-2-[2-(diphenylphosphino)phenyl]-4,5-dihydro-1,3-oxazol; In methanol; dichloromethane; under 775.743 Torr; for 18h; Bis(l,5-cyclooctadiene)diiridium(I) dichloride ([Ir(cod)Cl]2) (12.4 mg, 0.02 mmol) was added to the ligand (0.04 mmol) (49-53) in dichloromethane and stirred for 30 minutes. A-Methyl- 1 -phenyl ethan- 1 -imine (48) (100 mg, 0.75 mmol) and the preformed metal- ligand complex (0.04 mmol) were mixed in dichloromethane:methanol (8: 1) (9 mL) and stirred overnight under 15 bar H2 pressure.
  • 63
  • [ 19131-99-8 ]
  • [ 6907-71-7 ]
YieldReaction ConditionsOperation in experiment
With Streptomyces sp. GF3587 imine reductase; nicotinamide adenine dinucleotide phosphate In dimethyl sulfoxide at 20℃; Enzymatic reaction; 2.3 Determination of enzyme activity General procedure: The activities of the purified IREDs were determined from a liquid-phase spectrophotometric assay (Tecan infinite M200 pro, Männedorf, Swiss) monitoring the change of NADPH concentration at 340nm (=6.22mM-1cm-1). Reaction mixtures contained buffer (100mM, sodium phosphate pH 7.5 for the reduction or glycine-NaOH pH 10.5 for the oxidation), 0.2mM NADPH or 0.2mM NADP+ for the reduction or oxidation, respectively, in the presence of 5% (v/v) DMSO as cosolvent, and the substrate at the desired concentration. The reaction was started by adding the purified enzyme to the mixture. The reactions were performed at room temperature. One unit is defined as the amount of protein that oxidizes 1μmolNADPH/min. Controls were done using the same reaction composition but by substitution of enzyme or substrate with buffer. The reported activities are the mean of three purifications (from independent cultivations), each measured in triplicates.
  • 64
  • [ 19131-99-8 ]
  • (Sa)-1-[2-methoxycarbonyl-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid [ No CAS ]
  • (Sa)-methyl 2-[2-[methyl((S)-1-phenylethyl)carbamoyl]-1H-pyrrol-1-yl]-3-(trifluoromethyl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% Stage #1: (Sa)-1-[2-methoxycarbonyl-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid With thionyl chloride; N,N-dimethyl-formamide In toluene at 80℃; for 2h; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In toluene at 0℃; for 0.25h; 3 4.2 Typical procedure for the preparation of amido esters (Sa)-1a-g11 General procedure: (Sa)-1-[2-Methoxycarbonyl-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid 11 (8.00 mmol, 2.40 g, ee 99.8%) was dissolved in dry toluene (24 mL), and thionyl chloride (9.60 mmol, 0.70 mL) and one drop of dry DMF was added dropwise after which the reaction mixture was stirred at 80 °C for 2 h. The solvent was evaporated under reduced pressure. The residue was dissolved in dry toluene (25 mL) and a solution of amine (20.0 mmol) in 10 mL of dry toluene was added dropwise at 0 °C, after which the mixture was stirred for 15 min. A solution of hydrogen chloride (1 M, 25 mL) was then added, the phases were separated and the organic solution was washed with water (10 mL) then brine (10 mL) before drying over sodium sulfate and concentrated in vacuo.
  • 65
  • [ 19131-99-8 ]
  • [ 299917-90-1 ]
  • (3aR,8aR)-N,2,2-trimethyl-4,4,8,8-tetraphenyl-N-((S)-1-phenylethyl)tetrahydro-[1,3]-dioxolo[4,5-e][1,3,2]dioxaphosphepine-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With triethylamine In dichloromethane at 0 - 20℃; Molecular sieve; Inert atmosphere;
  • 66
  • [ 945668-51-9 ]
  • [ 19131-99-8 ]
  • (3aS,8aS)-N,2,2-trimethyl-4,4,8,8-tetraphenyl-N-((S)-1-phenylethyl)tetrahydro-[1,3]-dioxolo[4,5-e][1,3,2]dioxaphosphepine-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine In dichloromethane at 0 - 20℃; Molecular sieve; Inert atmosphere;
  • 67
  • [ 98-86-2 ]
  • [ 74-89-5 ]
  • [ 19131-99-8 ]
  • [ 5933-40-4 ]
  • 68
  • [ 19131-99-8 ]
  • [ 29892-37-3 ]
  • (Sp)-4-isocyano[2.2]paracyclophane [ No CAS ]
  • (Sp)-((methyl(1-phenylethyl)amino)((S)[2.2]paracyclophaneamino)methylene)gold(I) chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% Stage #1: chloro(dimethylsulfide) gold(I); (Sp)-4-isocyano[2.2]paracyclophane In dichloromethane at 20℃; for 0.25h; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In dichloromethane at 20℃; for 1h; Darkness; General procedure 1 (GP 1): synthesis of PCP-substituted NACgold(I) complexes General procedure: PCP-substituted NAC-gold(I) complexes were prepared according to a literature procedure [12]. One equivalent of (DMS)AuCl was dissolved in dry dichloromethane and one equivalent of PCP-isocyanide was added at room temperature. Then the mixture was stirred for 15 min. After that time 2 equivalents of the amine were added. The mixture was stirred at room temperature and protected from light for 1 h. The solution was filtered through celite and the solvent removed under reduced pressure. The solid was dissolved in DCM and pentane was added. The precipitate was collected on a frit, washed with pentane and dried in vacuum to afford the desired NAC gold complex as a colourless solid.
  • 69
  • [ 19131-99-8 ]
  • 7-[1-(tert-butoxycarbonyl)piperidin-4-yl]-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid [ No CAS ]
  • tert-butyl 4-(3-{methyl[(1S)-1-phenylethyl]carbamoyl}-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 18h; 440A Example 440A Tert-butyl 4-(3-{methyl[(lS)-l-phenylethyl]carbamoyl}-5-oxo-4,5-dihydropyrazolo[l,5-a]pyrimidin yl)piperidine- 1 -carboxylat To a solution of 7-[l-(tert-butoxycarbonyl)piperidin-4-yl]-5-oxo-4,5-dihydropyrazolo[l,5-a]pyrimidine- 3-carboxylic acid (150 mg, 414 μιηο) in dimethylformamide (1.5 ml, 19 mmol) were added HATU (205 mg, 538 μιηο) and N,N-Diisopropylethylamine (220 μ, 1.2 mmol). Then (lS)-N-methyl-l- phenylethanamine (112 mg, 828 μιηο) was added and the reaction mixture was stirred at RT for 16 h. More HATU (1.3 equivalents) was added and the reaction mixture was stirred at RT for 2 h. Water was added and the mixture was purified by preparative HPLC (Method: column: Reprosil C18; 10 μιη; 125x30 mm / flow: 50 ml/min / solvents: A = water (0,01% formic acid), B = acetonitrile / gradient: 0.00-2.00min = 20%B, 2.20min = 60%B, 8.00-12.00min = 90%B, 12.10-13.00min = 20%B). Evaporation of the combined product fractions yielded the title compound (88.3 mg, 96 % purity, 43 % of theory). LC-MS (Method IB): Rt = 1.14 min; MS (ESIpos): m z = 480 [M+H]+
  • 70
  • [ 19131-99-8 ]
  • 3-butoxy-4-methoxy-phenyl isocyanate [ No CAS ]
  • C21H28N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% In dichloromethane at 20℃; for 0.166667h; Example 16 Preparation Example 16 (S)-3-(3-butoxy-4-methoxy-phenyl)-1-methyl-1-(1-phenyl-ethyl)-urea Same manner as described in Preparative Example 3 (3), from 3-butoxy-4-methoxy-benzoic acid (50mg) The Preparation of 3-butoxy-4-methoxy-phenyl isocyanate, the isocyanate was dissolved in 5ml of dichloromethane. (S)-N-methyl-1-phenylethylamine (50mg), stirred for 10 minutes at room temperature, TLC the reaction was complete, the reaction solution was concentrated under reduced pressure. Silica gel column chromatography (petroleum ether / ethyl acetate = 5/1 elution) to give a white solid (S)-3-(3-butoxy-4-methoxy-phenyl)-1-methyl-1-(1-phenyl-ethyl)-urea, 41mg, 55% yield.
  • 71
  • [ 19131-99-8 ]
  • [ 381-97-5 ]
  • C4H5F3O2*C9H13N [ No CAS ]
  • C4H5F3O2*C9H13N [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 15% de 2: 4 % de In isopropyl alcohol at 20 - 70℃; 2 Screening of 80 chiral bases for the resolution of racemic α-CF3 propanoic acid to access (R)- and (S)-α-CF3 propanoic acid (1). General procedure: General procedure: To a solution of racemic acid 1 (5.68 mg, 0.04 mmol, 1 equiv) in IPA (0.2 mL, 0.2 M) was added the chiral base (0.04 mmol, 1 equiv as a 0.2 M stock solution in IPA). The resulting mixture was heated at 70 °C for 15 min to solubilize all the solids, and then allowed to cool naturally to ambient temperature with stirring overnight. Overall, 23 precipitates were obtained from the 80 combinations. The enantiomeric excess of the solid precipitate and the liquor for each reaction was analyzed by SFC.
  • 72
  • [ 19131-99-8 ]
  • [ 1187992-96-6 ]
  • (S)-4-hydroxy-N-methyl-N-(1-phenylethyl)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70.6% Stage #1: 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acid With triethylamine; 1,1'-carbonyldiimidazole In 1-methyl-pyrrolidin-2-one at 70℃; for 1h; Inert atmosphere; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In 1-methyl-pyrrolidin-2-one at 70℃; for 0.5h; Inert atmosphere;
  • 73
  • [ 19131-99-8 ]
  • [ 2616-50-4 ]
  • (-)-(S)-N-methyl-N-(1-phenylethyl)-3,4-dihydroquinoline-1(2H)-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With triethylamine In acetonitrile at 20℃; for 12h; Inert atmosphere;
  • 74
  • [ 19131-99-8 ]
  • (S)-5-biphenyl-4-yl-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid [ No CAS ]
  • C34H32N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h; 22 Example 22: (S)-5-Biphenyl-4-yl-4-(1 ,3-dihydro-isoindol-2-yl)-pentanoic acid methyl-(S-1 - phenyl-ethyl)-amide Example 22: (S)-5-Biphenyl-4-yl-4-(1 ,3-dihydro-isoindol-2-yl)-pentanoic acid methyl-(S-1 - phenyl-ethyl)-amide To a solution of (S)-5-biphenyl-4-yl-4-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2yl)-pentanoic acid (4.0 g 10 mmol) in 100 ml_ of CH2CI2 is added N-methyl-(S-1-phenyl-ethyl)amine (1.48 g, 11 mmol), EDC HCI ( 2.3g, 12mmol), HOBt (1.62 g, 12 mmol) and TEA (5 g, 50 mmol) sequentially and the mixture is stirred at room temperature for 12 h. After that the mixture is washed with water, dried and concentrated. The residue is purified by column chromatography (ethyl acetate/heptane = 1/2) to give (S)-5-biphenyl-4-yl-4-(1 ,3-dihydro-isoindol-2-yl)-pentanoic acid methyl-(S-1-phenyl-ethyl)-amide. 1 H NMR (CDCb): 1.39 ( 3H, d), 2.34 (3H, m), 2.51 (3H, s), 2.60 (1 H, m), 3.24 (1 H, m), 3.46 (1 H, m), 4.65 (1 H, m), 5.99 (1 H, m), 7.20-7.80 (18H, m, aromatic). HPLC method: Column: Eclipse XDB-C18; 150 χ 4.6 mm; 5 μηι. Mobile Phase A (0.1 % H3P04) in water; Mobile Phase B (Acetonitrile). Gradient: 0 min (30 % B); 8 min (95 % B); 15 min (95 % B). Flow rate: 1.0 ml min-1. Wavelength: 210 nm. Temperature: 30 °C. Retention time: 9.9 min
  • 75
  • [ 19131-99-8 ]
  • (S)-5-biphenyl-4-yl-4-dibenzylaminopentanoic acid hydrochloride [ No CAS ]
  • (S)-5-biphenyl-4-yl-4-dibenzylaminopentanoic acid methyl-((S)-1-phenylethyl)amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h; 18 Example 18: (S)- 5-Biphenyl-4-yl-4-dibenzylamino-pentanoic acid methyl-((S)-1-phenyl- ethyl)-amide Example 18: (S)- 5-Biphenyl-4-yl-4-dibenzylamino-pentanoic acid methyl-((S)-1-phenyl- ethyl)-amide The suspension of (S)-5-biphenyl-4-yl-4-dibenzylamino-pentanoic acid hydrochloride (4.86 g 10 mmol) in 10 ml_ of CH2CI2 is added (S)-methyl-(1-phenyl-ethyl)-amine (0.19 g, 1.36 mmol), EDC- HCI (0.29 g, 1.5 mmol), HOBt (0.21 g, 1.5 mmol) and TEA (0.63 g, 6.2 mmol) sequentially and the mixture is stirred at room temperature for 12 h. The reaction mixture is washed with water, dried and concentrated. The resulting residue is purified by column chromatography (ethyl acetate/heptane=1/5) to give (S)-5-biphenyl-4-yl-4-dibenzylamino-pentanoic acid methyl- ((S)-1-phenyl-ethyl)-amide. 1 H NMR (CDCI3): 1.40 (3H, d, CH3), 1.74 ( 1 H, m, 3-CHH), 1.90 (1 H, m, 3-CHH ), 2.50 (3H, s, CH3), 2.60 (2H, m, 2- CH2), 2.80 (2H, m, 5-CH2), 3.20 (1 H, dd, 4- CH), 3.57 (2H, d, CH2), 3.89 (2H, d, CH2), 6.02(1 H, q, CH), 7.10-7.50 (24H, m, aromatic). HPLC method: Column: Eclipse XDB-C18; 150 χ 4.6 mm; 5 μηι. Mobile Phase A (0.1 % H3P04) in water; Mobile Phase B (Acetonitrile). Gradient: 0 min (30 % B); 8 min (95 % B); 15 min (95 % B). Flow rate: 1.0 ml min-1. Wavelength: 210 nm. Temperature: 30 °C. Retention time: 1 1.1 min
  • 76
  • [ 4857-06-1 ]
  • [ 19131-99-8 ]
  • (S)-N-methyl-N-(1-phenylethyl)-1H-benzo[d]imidazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine at 200℃; for 24h; Sealed tube; 3.1. General Procedure for the Synthesis of Benzimidazole-Based Organocatalysts 1-10 General procedure: In a sealed pressure tube, a mixture of 2-chloro-1H-benzo[d]imidazole (0.5 mmol), the correspondingchiral amine 1 (2.5 equiv.), and Et3N (3 equiv.) was heated at 195-200 °C during 24 h. The reactionmixture was then allowed to reach room temperature. After the addition of H2O (5 mL), the mixturewas extracted with CH2Cl2 (3 x 5 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure to give the corresponding crude products, which were purifiedby flash chromatography (Hexane/EtOAc/MeOH). For the synthesis of benzimidazole 10, the sameprocedure was followed using 2-chloromethylbenzimidazole (0.5 mmol). The data shown belowcorrespond to the pure compounds:
  • 77
  • [ 19131-99-8 ]
  • 3-((2-((tert-butoxycarbonyl)imino)-4,4-diethyl-6-oxotetrahydropyrimidin-1(2H)-yl)methyl)-5-fluorobenzoic acid [ No CAS ]
  • (S)-tert-butyl (4,4-diethyl-1-(3-fluoro-5-(methyl(1-phenylethyl)carbamoyl)benzyl)-6-oxotetrahydropyrimidin-2(1H)-ylidene)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 15℃; for 16h; 9 Step 9: (S)-tert-butyl (4, 4-diethyl-l-(3-fluoro-5-(methyl(l-phenylethyl)carbamoyl)be) oxotetrahydropyrimidin-2(lH)-ylidene)carbamate DIEA (0.083 mL, 0.475 mmol) was added to a solution of EDCI (54.6 mg, 0.285 mmol), 3-((2-((tert-butoxycarbonyl)imino)-4,4-diethyl-6-oxotetrahydropyrimidin-l (2H)- yl)methyl)-5-fluorobenzoic acid (40 mg, 0.095 mmol), HOBT (25.6 mg, 0.190 mmol) and (S)-N- methyl-l-phenylethanamine (19.25 mg, 0.142 mmol) in THF (6 mL). The reaction was stirred at 15 °C for 16h. The mixture was quenched with water (10 mL), and extracted with ethyl acetate (10 mL x 3). The organic layers were washed with brine (20 mL), dried over Na2S04, filtered, and concentrated in vacuo to afford (S)-tert-butyl (4,4-diethyl-l -(3-fluoro-5-(methyl(l- phenylethyl)carbamoyl)benzyl)-6-oxotetrahydropyrirnidin-2(lH)-ylidene)carbamate. MS (ESI) m/z 539 [M+H]+.
  • 78
  • [ 19131-99-8 ]
  • 2,3-dihydro-4H-benzo[b]-[1,4]oxazine-4-carbonyl chloride [ No CAS ]
  • (-)-(S)-N-Methyl-N-(1-phenylethyl)-2,3-dihydro-4H-benzo[b]-[1,4]oxazine-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.07 g With triethylamine In acetonitrile at 20℃; Schlenk technique; Inert atmosphere; 4.3.1 (-)-(S)-N-Methyl-N-(1-phenylethyl)-2,3-dihydro-4H-benzo[b]-[1,4]oxazine-4-carboxamide (18) Synthesis of 2,3-dihydro-4H-benzo[b]-[1,4]oxazine-4-carbonyl chloride: to a solution of 44 triphosgene (3.4g, 12mmol, 0.46equiv) in anhydrous 45 CH2Cl2 (17mL, 0.7M) under a N2 atmosphere was added 46 pyridine (2.0mL, 25mmol, 1.0equiv) dropwise at -78°C. A solution of 29 3,4-dihydro-2H-benz-[b]-[1,4]oxazine (3.5g, 26mmol, 1.0equiv) in anhydrous CH2Cl2 (2mL) was added dropwise at -78°C before warming to room temperature. After completion, the reaction was quenched with 47 HCl (1.0M) and extracted three times with CH2Cl2. The combined organic layers were washed with saturated aqueous NaHCO3, dried over MgSO4, filtered and the resulting filtrate was concentrated under vacuum. The resulting residue was purified on a short pad of silica (eluting with 20% EtOAc/n-pentane) to give the 48 carbamoyl chloride. Preparation of 16 18: to a dried Schlenk flask under a N2 atmosphere was added a solution of 50 (S)-N-methyl-1-phenylethanamine (0.75mL, 3.9mmol, 1.3equiv) and 51 triethylamine (0.66mL, 4.8mmol, 1.6equiv) in anhydrous 52 acetonitrile (10mL, 0.4M). A solution of the 48 carbamoyl chloride (0.79g, 4.0mmol, 1.0equiv) in anhydrous acetonitrile (1mL) was added dropwise to the mixture and stirred at room temperature until completion (followed by TLC). The reaction was quenched with saturated 53 aqueous NaHCO3, extracted three times with CH2Cl2 and the combined organic layers were dried over MgSO4, filtered and the resulting filtrate was concentrated under vacuum. The crude urea was purified by flash column chromatography (eluting with 7-60% Et2O/petrol on a ZIP Sphere 30g column over 14 column volumes) to give the title compound 18; 1.07g, 90% yield; light yellow solid; Rf 0.18 (30% Et2O/n-pentane); mp 79-80°C (CH2Cl2/n-pentane); νmax (film)/cm-1 1642, 1601, 1584, 1496, 1431, 1391, 1338, 1306, 1282, 1217, 1178, 1061, 1050, 770; [α]21D [α]D21 =-43 (c 1.0, CHCl3); δH (400MHz, CDCl3) 7.37-7.28 (m, 5H, ArH), 6.96-6.93 (m, 1H, ArH), 6.87-6.86 (m, 1H, ArH), 6.81-6.77 (m, 1H, ArH), 5.59 (q, J=7.1Hz, 1H, NCHPh), 4.35-4.31 (m, 2H, CH2), 3.72-3.68 (m, 2H, CH2), 2.60 (s, 3H, NCH3), 1.61 (d, J=7.0Hz, 3H, CH3); δC (101MHz, CDCl3) 159.5 (C=O), 145.0 (C), 140.7 (C), 128.7 (CH), 128.4 (C), 127.6 (CH), 127.6 (CH), 123.1 (CH), 120.7 (CH), 119.5 (CH), 117.3 (CH), 66.4 (CH2), 54.4 (CH), 44.0 (CH2), 31.0 (CH3), 16.2 (CH3); HRMS (ESI+) [M+H]+ C18H21N2O2+ requires 297.1598; found 297.1607. Chiral supercritical fluid chromatography ((S,S)-Whelk-01, 5/100 Kromasil, 25cm×4.6mm ID), 125bar CO2, 40°C, 4mL/min, 20% co-solvent (MeOH); tR 3.8min (major), 5.2min (minor) 99:1 er. Racemic sample was prepared by making a 1:1 mixture of (-)-18 and (+)-18, which was prepared in an analogous manner.
  • 79
  • [ 19131-99-8 ]
  • [ 94-36-0 ]
  • (S)-O-benzoyl-N-methyl-N-(1-phenylethyl)hydroxylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With dipotassium hydrogenphosphate In N,N-dimethyl-formamide at 25℃; for 3h; Inert atmosphere;
  • 80
  • [ 19131-99-8 ]
  • (3R,5R,8R,9R,10S,13S,14S,17S)-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylic acid [ No CAS ]
  • C29H43NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% Stage #1: (3R,5R,8R,9R,10S,13S,14S,17S)-3-hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylic acid With triethylamine; HATU In N,N-dimethyl-formamide at 30℃; for 0.5h; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In N,N-dimethyl-formamide at 30℃; for 16h; 21 Example 21. Synthesis of compound 21 Step 1 (Compound 21). To a solution of A2 (100 mg, 0.3 12 mmol) in DMF (4 mL) was added TEA (156 mg, 1.55 mmol) and HATU (177 mg, 0.468 mmol) at 25 °C. After stirring at 30 °C for 30 mins, (S))-N-methyl-1-phenylethanamine (63.2 mg, 0.468 mmol) was added. The mixture was stirred at 30 °C for 16 h then treated with water (8 mL). The precipitate was collected by filtration and purified by HPLC (Waters Xbridge 150*25 5u, water (10mM NH4HCO3)-ACN, gradient: 55-85% B, flow rate: 25mL/min) to give Compound 21 (40 mg, 30%) as a solid.1H NMR (400 MHz, DMSO-d6) δ 7.40-7.32 (m, 2H), 7.21-7.29 (m, 3H), 6.02-5.72 (m, 1H), 3.94-3.81(m, 1H), 3.15-2.98 (m, 3H), 2.90-2.81 (m, 1H), 2.71-2.62 (m, 3H), 2.38-2.11 (m, 1H), 1.82-1.57 (m,8H), 1.57-1.20 (m, 1OH), 1.19-1.01 (s, 7H),0.74 (s, 3H). LCMS Rt = 1.174 min in 2 mm chromatography, 30-9OAB, purity 100%, MS ESI calcd. for C29H44N02 [M+H] 438, found 438.
  • 81
  • [ 19131-99-8 ]
  • [ 24424-99-5 ]
  • [ 173278-25-6 ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine In dichloromethane at 20℃; Inert atmosphere;
  • 82
  • [ 19131-99-8 ]
  • N-methyl-4,6-bis(perfluorophenoxy)-1,3,5-triazin-2-amine [ No CAS ]
  • (S)-N2,N4-dimethyl-6-(perfluorophenoxy)-N2-(1-phenylethyl)-1,3,5-triazine-2,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: N-methyl-4,6-bis(perfluorophenoxy)-1,3,5-triazin-2-amine With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.0833333h; Cooling with ice; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In dichloromethane at 0 - 40℃; for 24.0833h; Mel51: (S)-N2,N4-dimethyl-6-(perfluorophenoxy)-N2-(1-phenylethyl)-1,3,5-triazine-2,4-diamine DIPEA (30 mg, 0.22 mmol, 1.1 eq) was added to a solution of triazine 4b (94 mg, 0.2 mmol, 1 eq) in CH2Cl2 (3 mL) cooled in an ice water bath. After 5 min, a solution of (S)-N-methyl-1-phenylethylamine (30 mg, 0.22 mmol, 1.1 eq) in CH2Cl2 (1 ml) was added dropwise for 5 min at 0°C. The mixture was then stirred and heated to 40°C for 24 h, concentrated under reduced pressure and purified by column chromatography on silica gel, (CH2Cl2/Pentane: 80/20) to afford 68mg (81 %) of Mel51. 1H NMR: (400 MHz, CDCl3) δ 7.39-7.27(3H, m, CHar), 7.25-7.12 (2H, m, CHar), 6.06 (1H, br s, NH), 5.14 (1H, m, CH), 3.06-2.50 (6H, m, CH3, CH3), 1.62-1.43 (3H, m, CH3). LC-MS: m/z calcd. for C19 H16 F5 N5 O (M+H)+: 426.1267; found: 426.1340.
  • 83
  • [ 19131-99-8 ]
  • N-(2-(dimethylamino)ethyl)-4,6-bis(perfluorophenoxy)-1,3,5-triazin-2-amine [ No CAS ]
  • (S)-N2-(2-(dimethylamino)ethyl)-N4-methyl-6-(perfluorophenoxy)-N4-(1-phenylethyl)-1,3,5-triazine-2,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% Stage #1: N-(2-(dimethylamino)ethyl)-4,6-bis(perfluorophenoxy)-1,3,5-triazin-2-amine With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.0833333h; Cooling with ice; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In dichloromethane at 0 - 40℃; for 72.0833h; Mel43: (S)-N2-(2-(dimethylamino)ethyl)-N4-methyl-6-(perfluorophenoxy)-N4-(1-phenylethyl)-1,3,5-triazine-2,4-diamine DIPEA (30 mg, 0.22 mmol, 1.1 eq) was added to a solution of triazine 4c (113.68mg, 0.2 mmol, 1 eq) in CH2Cl2 (3 mL) cooled in an ice water bath. After 5 min, a solution of (S)-N-methyl-1-phenylethylamine (30 mg, 0.22 mmol, 1.1 eq) in CH2Cl2 (1 ml) was added dropwise for 5 min at 0°C. The mixture was then stirred and heated to 40°C for 72 h, concentrated under reduced pressure and purified by column chromatography on silica gel, (CH2Cl2/EtOH: 95/5), to afford 80 mg (83 %) of Mel43. 1H NMR: (400 MHz, CDCl3) δ 7.38-7.27 (4H, m, CHar), 7.23-7.10 (1H, br s, CHar), 6.02 (1H, br s, NH), 5.82-5.62 (1H, m, CH), 3.58-3.37 (2H, m, CH2), 2.90-2.63 (3H, m, CH3), 2.61-2.47 (2H, m, CH2), 2.40-2.21 (6H, m, CH3-N-CH3), 1.61-1.44 (3H, m, CH3). LC-MS: m/z calcd. for C22 H23 F5 N6 O (M+H)+: 483.1836; found: 483.1935.
  • 84
  • [ 19131-99-8 ]
  • (R)-2-(4,6-Bis(perfluorophenoxy)-1,3,5-triazin-2-ylamino)butan-1-ol [ No CAS ]
  • (R)-2-((4-(methyl((S)-1-phenylethyl)amino)-6-(perfluorophenoxy)-1,3,5-triazin-2-yl)amino)butan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% Stage #1: (R)-2-(4,6-Bis(perfluorophenoxy)-1,3,5-triazin-2-ylamino)butan-1-ol With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.0833333h; Cooling with ice; Stage #2: N-methyl-N-[(S)-1-phenylethyl]amine In dichloromethane at 0 - 40℃; for 24.0833h; Mel48: (R)-2-((4-(methyl((S)-1-phenylethyl)amino)-6-(perfluorophenoxy)-1,3,5-triazin-2-yl)amino)butan-1-ol DIPEA (30 mg, 0.22 mmol, 1.1 eq) was added to a solution of triazine 4d (106.45 mg, 0.2 mmol, 1 eq) in CH2Cl2 (3 mL) cooled in an ice water bath. After 5 min, a solution of (R)-1-phenylethylamine (30 mg, 0.22 mmol, 1.1 eq) in CH2Cl2 (1 ml) was added dropwise for 5 min at 0°C. The mixture was then stirred and heated to 40°C for 24 h, concentrated under reduced pressure and purified by column chromatography on silica gel, (CH2Cl2/AcOEt: 80/20), to afford 86 mg (89 %) of Mel48. 1H NMR: (400 MHz, CDCl3) δ 7.36-7.26 (4H, m, CHar),7.20 (1H, br s, CHar), 5.99 (1H, br s NH), 5.34-5.06 (1H, m, CH), 4.05-3.82 (1H, m, CH), 3.82-3.54 (2H, m, CH2), 2.90-2.59 (3H, m, CH3), 2.34 (H, br s, OH), 1.69-1.56 (2H, m,CH2),1.56-1.41(3H, m, CH3), 1.04-0.91 (3H, m, CH3). LC-MS: m/z calcd. for C22 H22 F5 N5 O2 (M+H)+: 484.1705; found: 484.1777.
  • 85
  • [ 19131-99-8 ]
  • [ 107-18-6 ]
  • (S)-N-methyl-N-(1-phenylethyl)prop-2-en-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With 1,1'-bis-(diphenylphosphino)ferrocene; nickel(II) bromide trihydrate; tetrabutylammonium acetate; zinc In N,N-dimethyl acetamide at 25℃; for 66h; Inert atmosphere;
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