2577-48-2|(S)-Methyl pyrrolidine-2-carboxylate| Ambeed

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine In dichloromethane for 10 h; Reflux	Thionyl chloride (20 ml, 0.275 mol) was added dropwise to a stirred suspension of (R)-proline (35a) (26.20 g, 0.228 mol) in MeOH (900 ml) at 0 °C. After the consumption of the starting material, methanol was evaporated under reduced pressure. The resulting solid was suspended in DCM (500 ml), and Et₃N (127 ml, 0.915 mol) and BnBr (33 ml, 0.275 mol) were added. The mixture was refluxed for 10 h. The solvent was evaporated and the product purified by flash chromatography on a silica gel using a linear gradient of EtOH in CHCl₃. The product was obtained as a light yellow oil in a 75percent yield (34.00 g, 0.159 mol). All spectral data recorded were in accordance with the literature data.

Yield	Reaction Conditions	Operation in experiment
80%	With formaldehyd; sodium acetate trihydrate In hydrogenchloride	42 b. N-Methyl proline methyl ester To a methanolic (250 mL) solution of L-proline methyl ester 10.42 g (62.92 mmol), sodium acetate trihydrate (8.6 g, 63.2 mmoL) and 37 wt percent aqueous formaldehyde (20 mL) was added 10percent Pd/C (1.05 g) and the reaction mixture placed under 4 atmosphere H2 pressure. Upon completion of the reaction the catalyst was removed by filtration, the methanolic solution concentrated and the residue dissolved in 10percent aq. HCl (~60 mL) and washed with ether (3100 mL), then the aqueous layer basified with K₂ CO₃ (solid) to pH~12 and extracted with CH₂ Cl₂ (375 mL), then the combined CH₂ Cl₂ layers dried (MgSO4) and concentrated to afford the crude product as a clear oil (7.19 g, 80percent). MS (DCl/NH₃) m/e (M+H)⁺, 1H-NMR (CDCl₃) δ: 1.78-2.03 (m, 3 H); 2.13-2.21 (m, 1H); 2.29-2.38 (m, 1 H); 2.42 (s, 3 H); 2.97-3.02 (3.13-3.19 (m, 1 H); 3.75 (s, 3 H).

1
[ 3257-18-9 ]
[ 2577-48-2 ]
[ 51220-78-1 ]

Reference： [1]Journal of the American Chemical Society,1956,vol. 78,p. 5883,5886
[2]Festschrift A. Stoll <Basel 1957> S. 468, 471,

2
[ 2577-48-2 ]
[ 7531-52-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With ammonia In methanol at 65℃; for 15h;
	With methanol; ammonia
	With ammonium hydroxide

With ammonium hydroxide In butan-1-ol at 5 - 30℃;

I Example ItPreparation of 2(S)-l-(chloro acetyl) pyrroHdine-2-carbonitriIe (formula- Ill) Example ItPreparation of 2(S)-l-(chloro acetyl) pyrroHdine-2-carbonitriIe (formula- Ill) To the 550 cc methanol charged 0.87 mole of formula-IV and stirred for 10-30 min at room temperature below 10°C preferably at 0±5°C. Added 1.45 mole thionylchloride at 40-70°C. After completion of reaction methanol was distilled out toobtain formula-V. Added 500cc 1-butanol and 60 cc aq. ammonia at 5-30°C and stirred for 30-60 mins. Filtered solid ammonium chloride and charged excess 600cc 1-butanol and 590cc aqueous ammonia at 5-30°C. After stirring for 10-14 hrs at ambient temperature separated butanol layer and solvent was distilled out to obtain formula- VI. To the degassed mass charged 375cc N, N-dimethylformamide and 0.82 mole chloro acetyl chloride and stirred at -5 to 25°C to produce formula- VII. Charged 0.47 mole phosphorous oxy chloride in the temperature range of -5 to 20 °C and stirred for l-2hrs.Then charged saturated sodium bi carbonate solution and extracted in lOOOcc ethyl acetate. Collected ethyl acetate layer and washed with 500cc saturated sodium chloride solution and distilled out ethyl acetate and crystallized with 2-isopropanol to afford nitrile compound of formula III with an yield of 40%. HPLC PURITY: 96-99%

Reference： [1]Nakamura, Akira; Mori, Yoshihiko; Oguni, Nobuki [Journal of the Chemical Society, Dalton Transactions, 1982, p. 2359 - 2362]
[2]Schnell; Karrer [Helvetica Chimica Acta, 1955, vol. 38, p. 2036]
[3]Peng, Jun; Feng, Yue; Tao, Zhu; Chen, Yingjie; Hu, Xiangnan [Letters in Organic Chemistry, 2013, vol. 10, # 3, p. 159 - 163]
[4]Current Patent Assignee: HARMAN FINOCHEM LTD - WO2015/92806, 2015, A1 Location in patent: Sheet 11

3
[ 67-56-1 ]
[ 147-85-3 ]
[ 2577-48-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride for 2h; Heating;
100%	With thionyl chloride Heating;
100%	With sulfuryl dichloride

98%	With thionyl chloride In methanol at 0 - 70℃; Inert atmosphere;	4.C.1 Synthesis of methyl L-prolinate (1) To a stirred solution of 4 L-proline (SM) (25 g, 217.3 mmol) in methanol (10 mL) was added 7 thionyl chloride (19 mL, 260.8 mmol) drop wise at 0°C. under argon atmosphere. The reaction mixture was allowed to stir at 70°C. for 16 h. After consumption of the starting material (by TLC), reaction mixture was brought to RT and volatiles were evaporated under reduced pressure to afford 5 compound 1 (35 g, 98%) as yellow color syrup. 1H-NMR: (500 MHz, DMSO-d6): δ 9.09 (s, 1H), 4.35-4.24 (m, 1H), 3.75 (s, 3H), 3.21-3.16 (m, 2H), 2.28-2.21 (m, 2H), 2.01-1.88 (m, 2H). LCMS (m/z): 130.1 [M++1]
96%	With Amberlyst 15 at 20℃;
96%	With dodeca-tungstophosphoric acid for 5h; Reflux;
95%	With thionyl chloride
95%	With thionyl chloride
95%	With thionyl chloride at 20℃;	1.1.1 The structural formula of L-valine methyl ester is as follows: The synthesis process is: with a thermometer,Mechanically stirred 500ml three-necked flask,Dissolve L-valine (1 eq) in anhydrous methanol at room temperature,Thionyl chloride (1.1 eq) was added dropwise,Stir at room temperature for 10-12h, after the reaction is completed,Directly unscrew the excess solvent from the system andChlorosulfoxide, adding a certain amount of dichloromethane,Wash the organic phase with a saturated aqueous solution of sodium carbonate.SeparatedMachine phase, steamed to get the product,Yield: 95%,
95%	With thionyl chloride at 20℃;	1 The synthesis process is: with a thermometer,Mechanically stirred 500ml three-necked flask,Dissolve L-proline (1 eq) in anhydrous methanol at room temperature,Thionyl chloride (1.1 eq) was added dropwise, and stirred at room temperature for 10-12 h.After the reaction is completed, directly remove the excess solvent of the system and the thionyl chloride.Add a certain amount of dichloromethane and wash the organic phase with a saturated aqueous solution of sodium carbonate.The organic phase is separated and evaporated to give the product.Yield: 95%
95%	With thionyl chloride at -15 - 60℃; Inert atmosphere;
95%	With thionyl chloride at 0℃; for 12h; Reflux;	1.2 Synthesis of L-proline methyl ester: Dissolve L-proline (1 equivalent) in anhydrous methanol in a 500mL round-bottom flask at 0°C, add thionyl chloride (1.2 equivalent) dropwise, after half an hour, slowly heat to 60°C and reflux Reaction for 12h. After TLC detects that the reaction of the raw materials is complete, stop the reaction, directly spin off the system excess solvent and thionyl chloride, extract 3 times with dichloromethane and water, and extract once with saturated brine. Collect the lower organic phase and dry with anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain the product, yield: 95%;
94%	With thionyl chloride Heating;
92%	With thionyl chloride at 20℃; for 12h;
91%	With thionyl chloride at 60℃; for 12h;	Methyl L-prolinate (13) To a solution of L-proline 12 (1.0 g, 8.69 mmol) in MeOH (10 mL), a freshly distilled thionyl chloride (940 µL, 3.04 mmol) was added slowly and stirred at room for 12 h at 60 °C. Upon the completion of reaction (as monitored by TLC), it was cooled to room temperature and methanol was removed under vacuum. The resulting material was dried under high vacuum affording the methyl ester of L-proline 13 (1.02 g, 91 %). 1H-NMR (300 MHz, CDCl3): δ = 3.76 (s, 3 H), 3.17 (m, 1 H), 3.10 (m, 2 H), 2.39 (m, 1 H), 2.14 (m, 1 H), 1.92 (m, 1 H), 1.80 (m, 1 H) ppm. FT-IR (neat): ν= 3450, 2920, 1640, 1745, 1260, 725 cm-1. HRMS (ESI); calcd. For C6H11NO2 [M+H] + =129.0789; Found 129.0790.
90%	Stage #1: <i>L</i>-proline With thionyl chloride In methanol at 0℃; Reflux; Stage #2: methanol With zinc at 20℃; for 3h;	(S)-methyl pyrrolidine-2-carboxylate (19) A mixture of 6.0 g (52 mmol) of L-proline and 150 mL of MeOH was cooled down to 0 °C in a water-ice bath and 5.7 mL (78 mmol,1.5 eq) of SOCl2 was added dropwise. The ice bath was replaced with an oil bath, and the flask was equipped with a reflux condenser protected from moist with a CaCl2 tube. The temperature of the oil bath was set to 90 °C. The reaction mixture was refluxed for 2 h and then cooled down to room temperature. The solvent was evaporated and 8.6 g of orange oil was obtained. This oil was dissolved in 500 mL of MeOH and to this mixture activated zinc dust (5.0 g) was added in one portion. The mixture was stirred for 3 h at room temperature and then was filtered and concentrated in vacuo. The amino ester was obtained as a yellow oil (6.06 g, 47 mmol, 90 %). Rf (10% CHCl3/MeOH) 0.14. [a]D 25 51.8 (c 1.0, CHCl3). 1H NMR (CDCl3, 300 MHz): d 6.21 (s, 1H), 4.36 (dd, J 8.7, 5.4 Hz, 1H), 3.80 (s, 3H), 3.36 (t, J 6.9 Hz, 2H), 2.45e2.21 (m,1H), 2.10e1.78 (m, 3H). 13C NMR (DMSO-d6, 75 MHz): d 172.4, 59.0, 52.3, 46.4, 28.8, 24.2. HRMS (ESI) m/z: calcd for C6H12NO2 [M+H]+, 130.0863; found, 130.0869.
89%	With thionyl chloride at 80℃;
80%	With amberlyst-15 Ambient temperature;
80%	With silica gel-immobilized perchloric acid at 80℃; for 5h; Inert atmosphere; Neat (no solvent); chemoselective reaction;
68%	With chloro-trimethyl-silane Heating;
68%	Stage #1: methanol; <i>L</i>-proline With chloro-trimethyl-silane at 50℃; Inert atmosphere; Stage #2: With potassium carbonate; sodium hydroxide In lithium hydroxide monohydrate Inert atmosphere;
68%	With chloro-trimethyl-silane at 50℃; Inert atmosphere;	Methyl prolinate (2). Chlorotrimethylsilane (95 g, 0.88 mol)was added to a solution of proline (25 g, 0.22 mol) in methanol(150 mL) with stirring, then the mixture was refluxed until evolution of hydrogen chloride stopped. The solvent was evaporated, water (10 mL) and diethyl ether (100 mL) were added to theresidue, followed by a dropwise addition of a solution of sodiumhydroxide (8.6 g) in water (26 mL). Then, potassium carbonate(30 g) was added to the mixture with stirring, the aqueous layerwas thrice extracted with diethyl ether (100 mL). The organiclayers were dried with potassium carbonate, the solvent was evaporated, the residue was distilled to obtain ester 2, the yield was 19 g(68%), b.p. 65 °C (6 Torr). Found (%): C, 55.57; H, 8.68.C6H11NO2. Calculated ( %): C, 55.79; H, 8.59. 1H NMR(CDCl3), δ: 2.34-2.40 (m, 1 H, NH); 3.65 (dd, 1 H, C(2)H,3JH,H = 5.7 Hz, 3JH,H = 8.6 Hz); 3.48 (s, 3 H, CH3O). 13C{1H}NMR (CDCl3), δ: 59.93 (s, C(2)); 47.14 (s, C(3)); 25.80 (s, C(4));30.33 (s, C(5)); 51.41 (s, CH3O); 175.80 (s, C(6)).
47%	With thionyl chloride
	With hydrogenchloride
	With hydrogenchloride
	With thionyl chloride for 16h; Heating;
	With thionyl chloride
	With thionyl chloride In methanol for 1h; Heating;
	With hydrogenchloride for 0.25h;
	With thionyl chloride at -20℃; for 6h;
	With thionyl chloride
	With thionyl chloride for 1h; Heating;
	With thionyl chloride Heating;
	With thionyl chloride
	With thionyl chloride Heating;
	With thionyl chloride for 36h;
	With thionyl chloride for 1h; Heating;
	With thionyl chloride at 20℃; for 12h;
	With thionyl chloride at 20℃; for 3.5h;
	Stage #1: methanol; <i>L</i>-proline With thionyl chloride Stage #2: With triethylamine In tetrahydrofuran
	With thionyl chloride
	Stage #1: methanol; <i>L</i>-proline With thionyl chloride at 0℃; Stage #2: With ammonium hydroxide In lithium hydroxide monohydrate
	With thionyl chloride Inert atmosphere; Reflux;
	With thionyl chloride	4.2. Starting materials General procedure: All solvents and reagents are commercially available and used as received. Ethyl (S)-N-benzylprolinate 4 and methyl (S)-prolinate 1b were prepared following a known protocol based on the treatment of the corresponding amino acid, dissolved in ethanol or methanol, with thionyl chloride.
	With chloro-trimethyl-silane at 80℃; for 8h;
	With thionyl chloride
	With thionyl chloride at 0℃;
	With thionyl chloride at 20℃; for 12h; Inert atmosphere;
	With thionyl chloride for 1h; Reflux;	4.2. Synthesis of (S)-N-[(tetrahydro-2H-thiopyran-4-yl)carbonyl]proline methyl ester (8) To cooled MeOH (8 ml) was slowly added SOCl2 (1.73 ml) keeping the temperature below0C. Then, (S)-proline (2.53 g, 21.97 mmol) was added, and the mixture was heated at refluxfor 1 h. Excess MeOH was evaporated, the sticky pale-yellow crude methyl (S)-prolinate (7)was dissolved in AcOEt (8 ml), Et3N (6.12 ml) and tetrahydro-2H-thiopyran-4-carbonyl chloride(6, 3.62 g, 21.97 mmol) (12) were added at 0C, and the mixture was stirred at r.t. overnight. Afterevaporation of AcOEt, the residue was dissolved in CH2Cl2, the solution was washed with sat.aqueous NaCl solution, dried over MgSO4, CH2Cl2 was evaporated, and the residue was distilled(bulb-to-bulb, 190C/5.10-2 mbar): 4.81 g (85%) of 8. Pale yellow oil: IR (film): 2951s, 1744s,1643s, 1434s, 1357m, 1303w, 1271m, 1239w, 1197s, 1175s, 1116w, 1096w, 1029w, 1012w,934m, 733m. 1H-NMR: 4.49-4.45 (m, CH(α)(Pro)); 3.72 (s, MeO); 3.68-3.65, 3.58-3.53 (2m,CH2(δ)(Pro)); 2.73-2.71 (m, CH2(2), CH2(6)(Tht)); 2.46-2.42 (m, CH(4)(Tht)); 2.20-2.06 (m, 3H); 2.02-1.89 (m, 5 H). 13C-NMR: 173.5, 172.7 (2s, 2C=O); 58.5 (d, CH(α)(Pro)); 52.0 (q, MeO);46.7 (t, CH2(δ)(Pro)); 42.5 (d, C(4)(Tht)); 30.1, 29.8 (2t, C(2), C(6)(Tht)); 29.5 (t, CH2(β)(Pro));27.7, 27.6 (2t, C(3), C(5)(Tht)); 24.7 (t, CH2(γ )(Pro)). CI-MS: 275 (30, [M + NH4]+), 258 (100,[M + H]+).
	With hydrogenchloride at 95℃; for 6h;	Acid hydrolysis of psychrophilin E General procedure: The compound (0.5 mg) was refluxed at 95°C for 6 h with 6N methanolic HCl. After cooling, the sample was evaporated under reduced pressure to dryness. Then, the remaining residue was dissolved in 1.0 mL of methylene chloride and 100 mL of TFAA and then it was refluxed at 60°C for 20 min. The sample was then cooled and the remaining liquid was evaporated at room temperature. The residue obtained was dissolved in methylene chloride for chiral gas GC analysis. The same procedure was conducted for an unequal known mixture of D- and L-proline standards. The configuration of proline was determined by an isothermic GC analysis using CP chirasil Dex CB column at 120°C over 15 min. Retention times (in min) for the standards were proline, R, 7.12 min, and S, 7.24 min. Analysis of the derivative gave a retention time of 7.24 min, determining an S configuration for the proline residue.
19.43 g	With thionyl chloride for 2.33333h; Cooling with ice;	Synthesis of (S)-1-( 4-sulfamoylbenzoyl)pyrrolidine-2-carboxylic acid 37 L-Proline (12.4 g,0.108 mol) was suspended in 50 mL of methanol, and the mixture was cooled in an ice bath.Thionyl chloride (8.1 mL, 0.11 mol) was added dropwise over twenty minutes. At the end of theaddition, the now homogenous mixture was removed from the ice bath, and allowed to stir for15 two hours before removal of all volatiles under vacuum, affording 19.43 grams of L-prolinemethyl ester which was used without any further purification.
	With thionyl chloride for 12h; Reflux; Inert atmosphere; Schlenk technique;
	With thionyl chloride at 0℃; for 4h; Reflux;
	With thionyl chloride at -5 - 70℃;	I Example ItPreparation of 2(S)-l-(chloro acetyl) pyrroHdine-2-carbonitriIe (formula- Ill) Example ItPreparation of 2(S)-l-(chloro acetyl) pyrroHdine-2-carbonitriIe (formula- Ill) To the 550 cc methanol charged 0.87 mole of formula-IV and stirred for 10-30 min at room temperature below 10°C preferably at 0±5°C. Added 1.45 mole thionylchloride at 40-70°C. After completion of reaction methanol was distilled out toobtain formula-V. Added 500cc 1-butanol and 60 cc aq. ammonia at 5-30°C and stirred for 30-60 mins. Filtered solid ammonium chloride and charged excess 600cc 1-butanol and 590cc aqueous ammonia at 5-30°C. After stirring for 10-14 hrs at ambient temperature separated butanol layer and solvent was distilled out to obtain formula- VI. To the degassed mass charged 375cc N, N-dimethylformamide and 0.82 mole chloro acetyl chloride and stirred at -5 to 25°C to produce formula- VII. Charged 0.47 mole phosphorous oxy chloride in the temperature range of -5 to 20 °C and stirred for l-2hrs.Then charged saturated sodium bi carbonate solution and extracted in lOOOcc ethyl acetate. Collected ethyl acetate layer and washed with 500cc saturated sodium chloride solution and distilled out ethyl acetate and crystallized with 2-isopropanol to afford nitrile compound of formula III with an yield of 40%. HPLC PURITY: 96-99%
	With thionyl chloride at 20℃; for 24h; Inert atmosphere;
	With thionyl chloride at 0℃; for 2h; Inert atmosphere;
	With thionyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h;
	With thionyl chloride at 0 - 20℃; for 18h;	390.1 Step-1: Preparation of methyl pyrrolidine-2-carboxylate Step-1: Preparation of methyl pyrrolidine-2-carboxylate: (0845) [00323] To a solution of L-proline (6 g, 52.11 mmol) in methanol (50 mL) cooled to 0 °C , was added thionyl chloride (4.92 mL, 67.74 mmol) drop-wise and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated to afford the title compound methyl pyrrolidine-2-carboxylate (9.6 g, crude) as a colourless liquid. Calculated (M+H): 130.08; Found (M+H): 130.2.
	With thionyl chloride In methanol at 0 - 25℃;
	With thionyl chloride at 0 - 20℃;	1 Example 1 Take L-proline (2g, 0.017mol) in a single-necked flask,Add 20mL of methanol,Temperature below 0 ,SOCl2 (2.48 g, 0.021 mol) was slowly added,Gradually returned to room temperature overnight, TLC detection reaction was complete.Concentrated under reduced pressure to give an oil, to give compound D1, which was directly cast in one step.
	With thionyl chloride at 0 - 20℃;	1 Example 1 Take L-proline (2g, 0.017mol) in a single-necked flask was added 20mL of methanol,Temperature below 0 , slowly add SOCl2 (2.48g, 0.021mol),Gradually returned to room temperature overnight, TLC detection reaction was complete.Concentrated under reduced pressure to give an oil, to give compound D1, which was directly cast in one step.
	With thionyl chloride at 0 - 20℃; for 3h; Inert atmosphere; Schlenk technique;
	With thionyl chloride
	Reflux; Acidic conditions;
	With thionyl chloride at 0℃; for 1h; Reflux;
	With thionyl chloride at 0 - 20℃; for 24h; Inert atmosphere; Schlenk technique;
	With thionyl chloride at 0 - 20℃; for 12h;
	With thionyl chloride at 0 - 20℃; for 20h; Inert atmosphere;
	With sulfuric acid at 70℃; for 24h;	1 EXAMPLE 1 Synthesis of amino acid methyl ester hydrochloride 3 g of L- proline was transferred into 100 mL RBF, 30 mL of methanol was added into the flask and placed on a magnetic stirrer at room temperature till proline was dissolved. 1.5 equiv (2.08 ml) of sulfuric acid was added into the reaction mixture dropwise with shaking and then refluxed at 70 °C for about 24 hours, the product was concentrated on a rotary evaporator and weight of the product was calculated for the next step. The reaction completion was checked in TLC using methanol: distilled water in a ratio of 1: 1 and then dipped in Ninhydrin solution then heated to observe the spots. (0046) [0034] (S)-methyl pyrrolidine-2 -carboxylate hydrochloride: White crystalline solid; 64% yield; M.P= 73 °C, IR (cm 1) = 1087.89 (C-O), 1745.64 (C=0), 3001 (C-H), 3328.28 (N-H); Mass (m/z) = 165.06.
	With thionyl chloride at 20℃; for 2h;	1.9 The ninth step: methyl L-prolinate (1L) L-proline (2g, 17.4mmol) was dissolved in 15mL methanol, thionyl chloride (2mL) was added at room temperature and the reaction was stirred for 2h. The reaction solution was adjusted to pH about 9 with saturated aqueous sodium bicarbonate solution, the aqueous phase was extracted with dichloromethane (30 mL×3), the organic phases were combined, and the organic phases were washed with water (20 mL×2), dried with anhydrous sodium sulfate, and concentrated. The obtained L-proline methyl ester (1L) was used directly in the next step.
	With thionyl chloride at 0 - 20℃; for 16h; Inert atmosphere;
	With thionyl chloride at 0 - 40℃; for 2h; Inert atmosphere;
	With thionyl chloride at 0 - 20℃;	Synthesis of L-Proline methyl ester In this method, L-proline (8.7 mmol, 1 g) was added to dry methanol(10 mL) and was kept untouched until the reaction mixture becameclear. The reaction mixture was then cooled up to 0 to 5 C, followed bya dropwise addition of thionyl chloride (SOCl2) (9.5 mmol, 1.136 g) intoit. The mixture was stirred at room temperature overnight, the solventwas removed, and the product so obtained was washed with ether anddried in a vacuum to get L-proline methyl ester having amine in theZwitterionic form. The aim is to require a free amine form; therefore, abasic condition was provided via the addition of a saturated solution ofsodium bicarbonate (NaHCO3) in it and extracted the organic aliquots inthe ethyl acetate solution. The excess solvent was removed throughevaporation to get a pure product. The completion of the reaction wasmonitored by TLC: Methanol/water (7:3).FTIR (KBr): 3314, 2104, 1633 and 1016 cm-1; 1H NMR (400 MHz,CDCl3): δ (ppm) = 4.6 (s, 3H, -OCH3), 4.03 (t, 1H -CH-NH), 3.33 (t, 1H-CH2-CH), 3.24 (t, 1H -CH2-CH), 2.273 (t, 1H -CH2-CH2), 2.242 (t,1H-CH2-CH2), 1.995 (s, 1H -NH-), 1.924 (q, 1H -CH2-NH), 1.907 (q,1H -CH2-NH). 13C NMR (400 MHz, CDCl3): δ (ppm) = 174.66 (-CO-),61.22 (-C-CO-), 48.87 (-OCH3), 46.07(-CH2-NH), 28.96(-CH2-CH2-CH) and 23.73(-CH2-CH2-CH2-).
	With thionyl chloride at -10℃; for 12h;	4.2.6 General procedure for the synthesis of compounds 17 and 18 [54] General procedure: l-Phenylalanine/l-Proline (1 equiv, 20mmol) was dissolved in methanol (20mL) at -10°C under stirring. SOCl2 (6mL) was added under nitrogen protection, and the reaction was stirred for 12h. Methanol (3×15mL) was then added. The resulting solution was concentrated to produce the corresponding ester in quantitative yield. Compound 17: 3.40g, 94.97% yield, white solid. Compound 18: 2.45g, 94.96% yield, transparent oil. The crude products were used for the next step directly without further purification.

Reference： [1]McNulty; Still [Tetrahedron Letters, 1991, vol. 32, # 37, p. 4875 - 4878]
[2]Sato, Tatsunori; Mori, Tomiyo; Sugiyama, Tadakatsu; Ishibashi, Hiroyuki; Ikeda, Masazumi [Heterocycles, 1994, vol. 37, # 1, p. 245 - 248]
[3]Tanzer, Eva-Maria; Zimmer, Lucie E.; Schweizer, W. Bernd; Gilmour, Ryan [Chemistry - A European Journal, 2012, vol. 18, # 36, p. 11334 - 11342,9]
[4]Current Patent Assignee: ABBVIE INC - US9994614, 2018, B2 Location in patent: Page/Page column 79; 80
[5]Kamal, Ahmed; Reddy, K. Laxma; Devaiah; Shankaraiah [Synlett, 2004, # 14, p. 2533 - 2536]
[6]Location in patent: experimental part Li, Jian-Guo; Peng, Yan-Qing [Journal of the Chinese Chemical Society, 2010, vol. 57, # 3 A, p. 305 - 308]
[7]Ding, Xiaobin; Vera, Matthew D.; Liang, Bo; Zhao, Yuming; Leonard, Michael S.; Joullie, Madeleine M. [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 2, p. 231 - 234]
[8]Kukula, Pavel; Prins, Roel [Journal of Catalysis, 2003, vol. 217, # 1, p. 240 - 244]
[9]Current Patent Assignee: SICHUAN ZHONGKE MICRO NANO TECH; NANKAI UNIVERSITY - CN109705014, 2019, A Location in patent: Paragraph 0086; 0090; 0091; 0092; 0093; 0094
[10]Current Patent Assignee: NANKAI UNIVERSITY; SICHUAN ZHONGKE MICRO NANO TECH - CN109851541, 2019, A Location in patent: Paragraph 0074; 0075; 0076; 0077
[11]Dong, Mengxian; Wang, Jie; Wu, Shijie; Zhao, Yang; Ma, Yangyang; Xing, Yongfei; Cao, Fei; Li, Longfei; Li, Zhenqiu; Zhu, Huajie [Advanced Synthesis and Catalysis, 2019, vol. 361, # 19, p. 4602 - 4610]
[12]Current Patent Assignee: NANKAI UNIVERSITY - CN112142638, 2020, A Location in patent: Paragraph 0108; 0135-0138
[13]Kelleher, Fintan; Kelly, Sinead [Tetrahedron Letters, 2006, vol. 47, # 18, p. 3005 - 3008] Kelleher, Fintan; Kelly, Sinead; McKee, Vickie [Tetrahedron, 2007, vol. 63, # 37, p. 9235 - 9242]
[14]Gao, Hong-Shuai; Hu, Zhi-Guo; Wang, Jian-Ji; Qiu, Zhao-Fa; Fan, Feng-Qiu [Australian Journal of Chemistry, 2008, vol. 61, # 7, p. 521 - 525]
[15]Kumar, Praveen; Rahman, Md. Ataur; Haque, Ashanul; Singh Yadav, Jhillu [Tetrahedron Letters, 2021, vol. 68]
[16]Lisiecki, Kamil; Krawczyk, Krzysztof K.; Roszkowski, Piotr; Maurin, Jan K.; Budzianowski, Armand; Czarnocki, Zbigniew [Tetrahedron, 2017, vol. 73, # 44, p. 6316 - 6328]
[17]Chu, Qian; Diedrich, Jolene K.; Vaughan, Joan M.; Donaldson, Cynthia J.; Nunn, Michael F.; Lee, Kuo-Fen; Saghatelian, Alan [Journal of the American Chemical Society, 2016, vol. 138, # 30, p. 9473 - 9478]
[18]Anand, Ramesh C.; Vimal [Synthetic Communications, 1998, vol. 28, # 11, p. 1963 - 1965]
[19]Chakraborti, Asit K.; Singh, Bavneet; Chankeshwara, Sunay V.; Patel, Alpesh R. [Journal of Organic Chemistry, 2009, vol. 74, # 16, p. 5967 - 5974]
[20]Prishchenko, A. A.; Livantsov, M. V.; Pisarnitskii, D. A.; Petrosyan, V. S. [Russian Journal of General Chemistry, 1993, vol. 63, # 9.1, p. 1410 - 1413][Zhurnal Obshchei Khimii, 1993, vol. 63, # 9, p. 2020 - 2025]
[21]Prishchenko, Andrey A.; Livantsov, Mikhail V.; Novikova, Olga P.; Livantsova, Ludmila I.; Petrosyan, Valery S. [Heteroatom Chemistry, 2017, vol. 28, # 1]
[22]Prishchenko; Livantsov; Novikova; Livantsova; Petrosyan [Russian Chemical Bulletin, 2016, vol. 65, # 7, p. 1846 - 1854][Izv. Akad. Nauk, Ser. Khim., 2016, vol. 65, # 7, p. 1846 - 1854,9]
[23]Current Patent Assignee: SANOFI; Translate Bio (in: Sanofi) - WO2018/13525, 2018, A1 Location in patent: Paragraph 00386
[24]Poroschin et al. [Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1959, p. 1851; engl. Ausg. S. 1768, 1769] Erlanger et al. [Journal of the American Chemical Society, 1954, vol. 76, p. 1806,1809] Schumann; Boissonnas [Helvetica Chimica Acta, 1952, vol. 35, p. 2237,2240]
[25]Shono, Tatsuya; Matsumura, Yoshihiro; Tsubata, Kenji; Uchida, Kenshi; Kanazawa, Takenobu; Tsuda, Kunio [Journal of Organic Chemistry, 1984, vol. 49, # 20, p. 3711 - 3716]
[26]Miles, Nicholas J.; Sammes, Peter G.; Kennewell, Peter D.; Westwood, Robert [Journal of the Chemical Society. Perkin transactions I, 1985, p. 2299 - 2306]
[27]Cran; Gibson; Handa [Tetrahedron Asymmetry, 1995, vol. 6, # 7, p. 1553 - 1556] Arakawa, Yasushi; Ohnishi, Masafumi; Yoshimura, Norikazu; Yoshifuji, Shigeyuki [Chemical and Pharmaceutical Bulletin, 2003, vol. 51, # 8, p. 1015 - 1020]
[28]Sato, Tatsunori; Kugo, Yasuhiro; Nakaumi, Erina; Ishibashi, Hiroyuki; ikeda, Masazumi [Journal of the Chemical Society. Perkin transactions I, 1995, # 14, p. 1801 - 1810]
[29]Baures, Paul W.; Ojalar, William H.; Costain, Willard J.; Ott, Michael C.; Pradhan, Ashish; Gleason, William B.; Mishra, Ram K.; Johnson, Rodney L. [Journal of Medicinal Chemistry, 1997, vol. 40, # 22, p. 3594 - 3600]
[30]Williamson, David A.; Bowler, Bruce E. [Journal of the American Chemical Society, 1998, vol. 120, # 42, p. 10902 - 10911]
[31]Montgomery, John; Chevliakov, Maxim V.; Brielmann, Harry L. [Tetrahedron, 1997, vol. 53, # 48, p. 16449 - 16462]
[32]Suter, Giovanni; Stojkova, Svetlana A.; Linden, Anthony; Heimgartner, Heinz [Helvetica Chimica Acta, 2000, vol. 83, # 11, p. 2961 - 2974] Breitenmoser, Roland A.; Heimgartner, Heinz [Helvetica Chimica Acta, 2002, vol. 85, # 3, p. 885 - 912] Xin, Zhuo-qun; Da, Chao-shan; Dong, Shou-liang; Liu, Da-xue; Wei, Jie; Wang, Rui [Tetrahedron Asymmetry, 2002, vol. 13, # 17, p. 1937 - 1940] Wei, Linyi; Brossi, Arnold; Kendall, Ross; Bastow, Kenneth F.; Morris-Natschke, Susan L.; Shi, Qian; Lee, Kuo-Hsiung [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 19, p. 6560 - 6569]
[33]Tanimori, Shinji; Fukubayashi, Kouji; Kirihata, Mitsunori [Tetrahedron Letters, 2001, vol. 42, # 24, p. 4013 - 4016]
[34]Xu, Kuo-Xi; Wu, Xiao-Jun; He, Yong-Bing; Liu, Shun-Ying; Qing, Guang-Yan; Meng, Ling-Zhi [Tetrahedron Asymmetry, 2005, vol. 16, # 4, p. 833 - 839]
[35]Ni, Yike; Zhao, Gang; Ding, Yu [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2000, # 19, p. 3264 - 3266]
[36]Déchamps, Ingrid; Pardo, Domingo Gomez; Cossy, Janine [Tetrahedron, 2007, vol. 63, # 37, p. 9082 - 9091]
[37]De La Fuente, M. Carmen; Dominguez, Domingo [Journal of Organic Chemistry, 2007, vol. 72, # 23, p. 8804 - 8810]
[38]Schmitkamp, Mike; Chen, Dianjun; Leitner, Walter; Klankermayer, Juergen; Francio, Giancarlo [Chemical Communications, 2007, # 39, p. 4012 - 4014]
[39]Gautier, Franois-Moana; Jones, Simon; Martin, Stephen J. [Organic and Biomolecular Chemistry, 2009, vol. 7, # 2, p. 229 - 231]
[40]Location in patent: body text Cardoso, Ana Lúcia; Lopes, Susana M.M.; Matos Beja, Ana; Ramos Silva, Manuela; de los Santos, Jesús M.; Pinho e Melo, Teresa M.V.D.; Palacios, Francisco [Tetrahedron, 2009, vol. 65, # 45, p. 9116 - 9124]
[41]Location in patent: scheme or table Hasse, Katrin; Willis, Anthony C.; Banwell, Martin G. [Australian Journal of Chemistry, 2009, vol. 62, # 7, p. 683 - 691] Location in patent: scheme or table Yu, Chuanming; Zheng, Fei; Ye, Haiwei; Zhong, Weihui [Tetrahedron, 2009, vol. 65, # 48, p. 10016 - 10021]
[42]Location in patent: experimental part Xu, Xiao-Wei; Wang, Xin-Long; Wu, Ai-Ming; Zheng, Zhi-Ming; Yi, Mei-Gui; Xiao, Rong [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 6, p. 1137 - 1141]
[43]Location in patent: body text Elmarrouni, Abdelatif; Fukuda, Aya; Heras, Montserrat; Arseniyadis, Stellios; Cossy, Janine [Journal of Organic Chemistry, 2010, vol. 75, # 24, p. 8478 - 8486]
[44]Location in patent: experimental part Mloston, Grzegorz; Pieczonka, Adam M.; Wroblewska, Aneta; Linden, Anthony; Heimgartner, Heinz [Tetrahedron Asymmetry, 2012, vol. 23, # 10, p. 795 - 801]
[45]Jaeger, Robert J. R.; Lamshoeft, Marc; Gottfried, Sebastian; Spiteller, Michael; Spiteller, Peter [Journal of Natural Products, 2013, vol. 76, # 2, p. 127 - 134]
[46]Heescher, Carolin; Schollmeyer, Dieter; Nubbemeyer, Udo [European Journal of Organic Chemistry, 2013, # 20, p. 4399 - 4404]
[47]Karpoormath, Rajshekhar; Sayed, Yasien; Govender, Thavendran; Kruger, Hendrik G.; Soliman, Mahmoud E. S.; Maguire, Glenn E. M. [Medicinal Chemistry Research, 2013, vol. 22, # 8, p. 3918 - 3933]
[48]Feu, Karla Santos; Deobald, Anna Maria; Narayanaperumal, Senthil; Correa, Arlene G.; Weber Paixao, Marcio [European Journal of Organic Chemistry, 2013, # 26, p. 5917 - 5922]
[49]Stoykova, Svetlana A.; Linden, Anthony; Heimgartner, Heinz [Journal of Sulfur Chemistry, 2014, vol. 35, # 1, p. 14 - 23]
[50]Ebada, Sherif S.; Fischer, Thomas; Hamacher, Alexandra; Du, Feng-Yu; Roth, Yoen Ok; Kassack, Matthias U.; Wang, Bin-Gui; Roth, Eckhard H. [Natural Product Research, 2014, vol. 28, # 11, p. 776 - 781]
[51]Current Patent Assignee: EVESTRA; EVESTRA INK - WO2015/6691, 2015, A1 Location in patent: Page/Page column 45; 46
[52]Lee, Way-Zen; Chiang, Chien-Wei; Kulkarni, Girish M.; Kuo, Ting-Shen [Journal of the Chinese Chemical Society, 2013, vol. 60, # 3, p. 245 - 250]
[53]Paz, Nieves R.; Rodríguez-Sosa, Dionisio; Valdés, Haydee; Marticorena, Ricardo; Melián, Daniel; Copano, M. Belén; González, Concepción C.; Herrera, Antonio J. [Organic Letters, 2015, vol. 17, # 10, p. 2370 - 2373]
[54]Current Patent Assignee: HARMAN FINOCHEM LTD - WO2015/92806, 2015, A1 Location in patent: Sheet 11
[55]Rioton, Sarah; Orliac, Aurélie; Antoun, Zeina; Bidault, Roselyne; Gomez Pardo, Domingo; Cossy, Janine [Organic Letters, 2015, vol. 17, # 12, p. 2916 - 2919]
[56]Rayner, Peter J.; Smith, Joshua C.; Denneval, Charline; O'Brien, Peter; Clarke, Paul A.; Horan, Richard A. J. [Chemical Communications, 2016, vol. 52, # 7, p. 1354 - 1357]
[57]Heinrich, Timo; Buchstaller, Hans-Peter; Cezanne, Bertram; Rohdich, Felix; Bomke, Jörg; Friese-Hamim, Manja; Krier, Mireille; Knöchel, Thorsten; Musil, Djordje; Leuthner, Birgitta; Zenke, Frank [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 3, p. 551 - 556]
[58]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2017/100591, 2017, A1 Location in patent: Paragraph 00323
[59]Yang, Dezhi; Tong, Dongdong; Zhang, Qian; Wang, Yongtao; Sun, Jing; Zhang, Fenghe; Zhao, Guisen [Chemical Biology and Drug Design, 2017, vol. 90, # 5, p. 791 - 803]
[60]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN107235884, 2017, A Location in patent: Paragraph 0051; 0065; 0066; 0101; 0102; 0113; 0114
[61]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN107235965, 2017, A Location in patent: Paragraph 0076; 0077; 0112; 0113; 0124
[62]Poplata, Saner; Bach, Thorsten [Journal of the American Chemical Society, 2018, vol. 140, # 9, p. 3228 - 3231]
[63]Sweed, Ayman M. K.; Senge, Mathias O.; Atta, Sanaa M. Sh.; Farrag, Dalia S.; Abdel-Rahman, Abdel-Rahman H.; Shaker, Yasser M. [Journal of Porphyrins and Phthalocyanines, 2018, vol. 22, # 11, p. 997 - 1009]
[64]Katakam, Nanda Kumar; Seifert, Cole W.; D'Auria, John; Li, Guigen [Heterocycles, 2019, vol. 99, # 1, p. 604 - 613]
[65]Kilpeläinen, Tommi P.; Tyni, Jonna K.; Lahtela-Kakkonen, Maija K.; Eteläinen, Tony S.; Myöhänen, Timo T.; Wallén, Erik A. A. [ACS Medicinal Chemistry Letters, 2019, vol. 10, # 12, p. 1635 - 1640]
[66]Leverenz, Malte; Merten, Christian; Dreuw, Andreas; Bach, Thorsten [Journal of the American Chemical Society, 2019, vol. 141, # 51, p. 20053 - 20057]
[67]Debia, Natalí P.; Rodríguez, Juan J.P.; da Silveira, Carolina H.; Chaves, Otavio A.; Iglesias, Bernardo A.; Rodembusch, Fabiano S.; Lüdtke, Diogo S. [Journal of Molecular Liquids, 2020, vol. 309]
[68]Eschmann, Christian; Song, Lijuan; Schreiner, Peter R. [Angewandte Chemie - International Edition, 2021, vol. 60, # 9, p. 4823 - 4832][Angew. Chem., 2021, vol. 133, # 9, p. 4873 - 4882,10]
[69]Current Patent Assignee: LOVELY PROFESSIONAL UNIV - WO2021/9768, 2021, A1 Location in patent: Paragraph 0033-0034
[70]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112442029, 2021, A Location in patent: Paragraph 0273; 0277; 0314-0318
[71]Sousa E Silva, Felipe Cesar; Doktor, Katarzyna; Michaudel, Quentin [Organic Letters, 2021, vol. 23, # 13, p. 5271 - 5276]
[72]Ning, Xiang-Li; Li, Yu-Zhi; Huo, Cui; Deng, Ji; Gao, Cheng; Zhu, Kai-Rong; Wang, Miao; Wu, Yu-Xiang; Yu, Jun-Lin; Ren, Ya-Li; Luo, Zong-Yuan; Li, Gen; Chen, Yang; Wang, Si-Yao; Peng, Cheng; Yang, Ling-Ling; Wang, Zhou-Yu; Wu, Yong; Qian, Shan; Li, Guo-Bo [Journal of Medicinal Chemistry, 2021, vol. 64, # 12, p. 8303 - 8332]
[73]Lakhani, Pratikkumar; Modi, Chetan K. [Molecular catalysis, 2022, vol. 525]
[74]Cheng, Keguang; Liu, Jingjing; Liu, Yanghan; Sheng, Lixin; Si, Yang; Wen, Xiaoan; Yin, Yudong; Zhang, Juzheng; Zhang, Liqiong [Bioorganic Chemistry, 2022, vol. 126]

4
[ 2065-37-4 ]
[ 2577-48-2 ]
[ 64940-12-1 ]

Reference： [1]Journal of Organic Chemistry,1980,vol. 45,p. 1260 - 1270

5
[ 13734-41-3 ]
[ 2577-48-2 ]
[ 38017-75-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In dichloromethane
70%	With triethylamine; dicyclohexyl-carbodiimide In chloroform at 20℃; for 24h;
63.7%	Stage #1: t-Boc-L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.25h; Stage #2: methyl (2S)-pyrrolidine carboxylate With benzotriazol-1-ol In dichloromethane for 24h;	2.3.Synthesis of dipeptides (L₁, L₂) General procedure: Boc-amino acid (10mmol) was dissolved in dichloromethane (DCM, 20mL). To this solution, EDCI (4.77g, 25mmol) was added at 0°C and the reaction mixture was stirred for 15min amino acid methylester (10mmol) was added followed by HOBT (2.74g, 20mmol) to the above reaction mixture under stirring. After 24h, the reaction mixture was filtered; the residue was washed with DCM (30mL) and added to the filtrate. The filtrate was washed with 5% sodium bicarbonate and saturated sodium chloride solutions. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography.

58%	Stage #1: t-Boc-L-valine; methyl (2S)-pyrrolidine carboxylate With triethylamine In dichloromethane for 1h; Stage #2: With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h;
57%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 20h;
	With dicyclohexyl-carbodiimide In dichloromethane
	With 4-methyl-morpholine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane

Reference： [1]Sun, Haiying; Nikolovska-Coleska, Zaneta; Chen, Jianyong; Yang, Chao-Yie; Tomita, York; Pan, Hongguang; Yoshioka, Yoshiko; Krajewski, Krzysztof; Roller, Peter P.; Wang, Shaomeng [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 3, p. 793 - 797]
[2]Belagali; Himaja; Kumar; Thomas; Prakasini; Poojary [Bollettino Chimico Farmaceutico, 1999, vol. 138, # 4, p. 160 - 164]
[3]Arjmand, Farukh; Jamsheera; Mohapatra [Journal of Photochemistry and Photobiology B: Biology, 2013, vol. 121, p. 75 - 85]
[4]Sansinenea, Estibaliz; Salazar, Francisco; Jiménez, Jacqueline; Mendoza, Ángel; Ortiz, Aurelio [Tetrahedron Letters, 2016, vol. 57, # 24, p. 2604 - 2607]
[5]Agbowuro, Ayodeji A.; Hwang, Jimin; Peel, Emma; Mazraani, Rami; Springwald, Alexandra; Marsh, James W.; McCaughey, Laura; Gamble, Allan B.; Huston, Wilhelmina M.; Tyndall, Joel D.A. [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 18, p. 4185 - 4199]
[6]Smith, Grant Gill; Evans, Robert C.; Baum, Rocky [Journal of the American Chemical Society, 1986, vol. 108, # 23, p. 7327 - 7332]
[7]Domzalski, Alison; Margent, Liliana; Vigo, Valeria; Dewan, Faizunnahar; Pilarsetty, Naga Vara Kishore; Xu, Yujia; Kawamura, Akira [Molecules, 2021, vol. 26, # 19]

6
[ 15761-38-3 ]
[ 2577-48-2 ]
[ 33300-71-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	1 Step 1 - Methyl (2S)-1-[(2S)-2-[(tert-butoxycarbonyl)amino]propanoyl]pyrrolidine-2- carboxylate To a stirred solution of (2S)-2-[(tert-butoxycarbonyl)amino]propanoic acid (5.00 g, 26.43 mmol) and methyl (2S)-pyrrolidine-2-carboxylate hydrochloride (5.69 g, 34.35 mmol) in DMF (50.00 mL) were added DIEA (13.66 g, 105.7 mmol) and HBTU (13.03 g, 34.35 mmol) in turns at rt under nitrogen atmosphere. The resulting mixture was stirred for 2 h at rt under nitrogen atmosphere. On completion, the reaction mixture was diluted with water (400 mL) and the mixture was extracted with EtOAc (5 x100 mL). The combined organic layers were washed with brine (5 x 250mL), and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reverse phase flash chromatography (Column: WelFlash TM C18-I, 20-40 um, 330 g; Eluent A: Water (10 mmol/L NH4HCO3); Eluent B: ACN; Gradient: 20% - 40% B in 25 min; Flow rate: 80 mL/min; Detector: 220/254 nm; desired fractions were collected at 35% B) and concentrated under reduced pressure to afford the title compound (7.38 g, 93% yield) as a yellow oil.1H NMR (300 MHz, DMSO-d6) δ 6.95 (d, J=7.5 Hz, 1H), 4.36-4.32 (m, 1H), 4.29-4.25 (m, 1H), 3.68-3.64 (m, 1H), 3.62 (s, 3H), 3.58-3.52 (m, 1H), 2.28-2.11 (m, 1H), 1.97-1.93 (m, 2H), 1.85-1.81 (m, 1H), 1.38 (s, 9H), 1.19-1.13 (m, 3H); LC/MS (ESI, m/z): [(M + H)]+ = 301.1
67.2%	Stage #1: L-N-Boc-Ala With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.25h; Stage #2: methyl (2S)-pyrrolidine carboxylate With benzotriazol-1-ol In dichloromethane for 24h;	2.3.Synthesis of dipeptides (L₁, L₂) General procedure: Boc-amino acid (10mmol) was dissolved in dichloromethane (DCM, 20mL). To this solution, EDCI (4.77g, 25mmol) was added at 0°C and the reaction mixture was stirred for 15min amino acid methylester (10mmol) was added followed by HOBT (2.74g, 20mmol) to the above reaction mixture under stirring. After 24h, the reaction mixture was filtered; the residue was washed with DCM (30mL) and added to the filtrate. The filtrate was washed with 5% sodium bicarbonate and saturated sodium chloride solutions. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography.
	With dicyclohexyl-carbodiimide In dichloromethane

With dmap; dicyclohexyl-carbodiimide In dichloromethane for 1h; Inert atmosphere;

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - WO2021/188696, 2021, A1 Location in patent: Paragraph 00927; 00928
[2]Arjmand, Farukh; Jamsheera; Mohapatra [Journal of Photochemistry and Photobiology B: Biology, 2013, vol. 121, p. 75 - 85]
[3]Smith, Grant Gill; Evans, Robert C.; Baum, Rocky [Journal of the American Chemical Society, 1986, vol. 108, # 23, p. 7327 - 7332]
[4]Kang, Seock Yong; Park, Yong Sun [European Journal of Organic Chemistry, 2012, # 9, p. 1703 - 1706]

7
[ 1738-87-0 ]
[ 2577-48-2 ]
[ 49761-04-8 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1984,vol. 93,p. 73 - 82

8
[ 24424-99-5 ]
[ 2577-48-2 ]
[ 59936-29-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In N,N-dimethyl-formamide at 60℃; for 0.5h;
100%	With perchloric acid at 30 - 35℃; for 0.166667h;
96%	With 1-methylimidazolium tetrafluoroborate at 30 - 35℃; for 0.166667h;

94%	With dmap; triethylamine In dichloromethane for 18h; Ambient temperature;
93%	With triethylamine In dichloromethane at 0 - 20℃; for 16h;	1.1.2 (2) Synthesis of N-Boc-(L)-valine methyl ester The synthesis process is:L-valine methyl ester (1 eq) was dissolved in dichloromethane, triethylamine (2.2 eq) was added, di-tert-butyl dicarbonate (1.1 eq) was added dropwise at zero, and the system was reacted at room temperature. After 16 hours, after the reaction is completed, a certain amount of 0.5N hydrochloric acid solution is added to wash the organic phase, and the organic phase is separated, the organic phase is separated, and the organic phase is washed with a saturated aqueous solution of sodium hydrogencarbonate, and finally washed with saturated brine and dried. , steamed to get the product,Yield: 93%,
93%	With triethylamine In dichloromethane at 0 - 20℃;	1.2 Synthesis of N-Boc-L-proline methyl ester: Dissolve L-proline methyl ester (1 equivalent) in dry dichloromethane, add triethylamine (2.2 equivalent), add di-tert-butyl dicarbonate (1.1 equivalent) dropwise to it at 0°C, slowly increase To room temperature, react for 10-16 hours. After the reaction was detected by TLC, it was extracted three times with dichloromethane and 1N HCl solution, washed with saturated brine, and the lower organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain the product. Yield: 93%;
91%	In N,N-dimethyl-formamide for 4h;
90%	With indium(III) bromide at 30 - 35℃; for 0.25h;
85%	With triethylamine In dichloromethane
74%	With dmap; triethylamine In dichloromethane at 20℃;
	With triethylamine
		1 Proline methyl or ethyl ester 1 is protected with a suitable protecting group like tert-butyloxycarbonyl using a reagent like boc anhydride and reduced with a reducing agent like DIBAL in a noprotic solvent like THF to give the aldehyde 3. Addition of vinyl magnesium bromide gives the alcohol 4, which is protected with a suitable protecting group like benzoate 5 by treatment with benzoyl chloride in the presence of a base like pyridine. Deprotection of the amino group of 5 followed by allylation affords the intermediate 7. 7 is subjected to ring closing metathesis with a suitable catalyst like first or second generation Grubb's catalyst or a further modified version of the catalyst to give the indolizidine scaffold 8. Further functionalization of the olefin by treatment with an oxidizing agent like m-CPBA or urea-hydrogen peroxide complex affords the epoxide 9. Opening of the epoxide under acidic condition can afford products like the 6-deoxycastanospermine analogs 10.
	With triethylamine
	In dichloromethane at 20℃; for 12h; Inert atmosphere;
	With triethylamine In <i>tert</i>-butyl alcohol at 25℃; for 21h;
11 g	With triethylamine In dichloromethane at 0 - 20℃; for 18h;	390.2 Ste -2: (0846) Preparation of 1-tert-butyl 2-methyl pyrrolidine-1,2-dicarboxylate Ste -2: (0846) Preparation of 1-tert-butyl 2-methyl pyrrolidine-1,2-dicarboxylate: (0847) [00324] To a solution of methyl pyrrolidine-2-carboxylate (9.6 g, 74.41 mmol) and triethylamine (15.55 mL, 111.62 mmol) in dichloromethane (200 mL) cooled to 0 °C, was added Boc anhydride (20.5 mL, 89.30 mmol) drop-wise and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with dichloromethane (200 mL) and washed with water (2 x 200 mL). The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated. The crude product was purified by silica gel column chromatography using 20% ethyl acetate in hexane to afford the title compound 1-tert-butyl 2- methyl pyrrolidine-1,2-dicarboxylate (11 g, 93% yield) as a colourless liquid. Calculated (M+H): 230.13; Found (M+H): 130.2 [Boc deprotected mass observed].
	With triethylamine In dichloromethane at 0 - 25℃;
80.8 mg	With sodium hydroxide In water; acetonitrile for 0.5h; Inert atmosphere;
	With triethylamine In dichloromethane at 0 - 20℃; for 12h;
2.55 g	With sodium hydrogencarbonate In water at 20℃; for 5h;	1.10 The tenth step: 1-(tert-butyl)2-methyl(S)-pyrrolidine-1,2-dicarboxylate (1M) 1L (2g, 15.5mmol) was dissolved in 15mL of THF, 10mL of saturated aqueous sodium bicarbonate solution was added, di-tert-butyl dicarbonate (4.39g, 20mmol) was added at room temperature and the reaction was stirred for 5h. The aqueous phase was extracted with ethyl acetate (60 mL×3), the organic phases were combined, the organic phase was washed with water (40 mL×2), dried over anhydrous sodium sulfate, concentrated, and the crude product was separated and purified by silica gel column chromatography (ethyl acetate/petroleum ether ( v/v)=1:50-1:25) to obtain 1-(tert-butyl)-2-methyl(S)-pyrrolidine-1,2-dicarboxylate (1M) (2.55g, yield : 71%)
	With dmap; triethylamine In dichloromethane at 20℃; for 1.5h; Inert atmosphere;

Reference： [1]McNulty; Still [Tetrahedron Letters, 1991, vol. 32, # 37, p. 4875 - 4878]
[2]Chakraborti, Asit K.; Chankeshwara, Sunay V. [Organic and Biomolecular Chemistry, 2006, vol. 4, # 14, p. 2769 - 2771]
[3]Sunitha, Sadula; Kanjilal, Sanjit; Reddy, P. Srinivasa; Prasad, Rachapudi B.N. [Tetrahedron Letters, 2008, vol. 49, # 16, p. 2527 - 2532]
[4]Jones; Woo [Tetrahedron, 1991, vol. 47, # 34, p. 7179 - 7184]
[5]Current Patent Assignee: SICHUAN ZHONGKE MICRO NANO TECH; NANKAI UNIVERSITY - CN109705014, 2019, A Location in patent: Paragraph 0086; 0090; 0095; 0096; 0097; 0098
[6]Current Patent Assignee: NANKAI UNIVERSITY - CN112142638, 2020, A Location in patent: Paragraph 0108; 0135; 0139-0141
[7]Miles, Nicholas J.; Sammes, Peter G.; Kennewell, Peter D.; Westwood, Robert [Journal of the Chemical Society. Perkin transactions I, 1985, p. 2299 - 2306]
[8]Chankeshwara, Sunay V.; Chakraborti, Asit K. [Synthesis, 2006, # 16, p. 2784 - 2788]
[9]Ding, Xiaobin; Vera, Matthew D.; Liang, Bo; Zhao, Yuming; Leonard, Michael S.; Joullie, Madeleine M. [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 2, p. 231 - 234]
[10]Kelleher, Fintan; Kelly, Sinead [Tetrahedron Letters, 2006, vol. 47, # 18, p. 3005 - 3008] Kelleher, Fintan; Kelly, Sinead; McKee, Vickie [Tetrahedron, 2007, vol. 63, # 37, p. 9235 - 9242]
[11]Cran; Gibson; Handa [Tetrahedron Asymmetry, 1995, vol. 6, # 7, p. 1553 - 1556]
[12]Current Patent Assignee: PFIZER INC - US2006/241306, 2006, A1 Location in patent: Page/Page column 1-2
[13]Location in patent: scheme or table Yu, Chuanming; Zheng, Fei; Ye, Haiwei; Zhong, Weihui [Tetrahedron, 2009, vol. 65, # 48, p. 10016 - 10021]
[14]Feu, Karla Santos; Deobald, Anna Maria; Narayanaperumal, Senthil; Correa, Arlene G.; Weber Paixao, Marcio [European Journal of Organic Chemistry, 2013, # 26, p. 5917 - 5922]
[15]Heinrich, Timo; Buchstaller, Hans-Peter; Cezanne, Bertram; Rohdich, Felix; Bomke, Jörg; Friese-Hamim, Manja; Krier, Mireille; Knöchel, Thorsten; Musil, Djordje; Leuthner, Birgitta; Zenke, Frank [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 3, p. 551 - 556]
[16]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2017/100591, 2017, A1 Location in patent: Paragraph 00324
[17]Yang, Dezhi; Tong, Dongdong; Zhang, Qian; Wang, Yongtao; Sun, Jing; Zhang, Fenghe; Zhao, Guisen [Chemical Biology and Drug Design, 2017, vol. 90, # 5, p. 791 - 803]
[18]Speckmeier, Elisabeth; Klimkait, Michael; Zeitler, Kirsten [Journal of Organic Chemistry, 2018, vol. 83, # 7, p. 3738 - 3745]
[19]Debia, Natalí P.; Rodríguez, Juan J.P.; da Silveira, Carolina H.; Chaves, Otavio A.; Iglesias, Bernardo A.; Rodembusch, Fabiano S.; Lüdtke, Diogo S. [Journal of Molecular Liquids, 2020, vol. 309]
[20]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112442029, 2021, A Location in patent: Paragraph 0273; 0277; 0319-0323
[21]Ning, Xiang-Li; Li, Yu-Zhi; Huo, Cui; Deng, Ji; Gao, Cheng; Zhu, Kai-Rong; Wang, Miao; Wu, Yu-Xiang; Yu, Jun-Lin; Ren, Ya-Li; Luo, Zong-Yuan; Li, Gen; Chen, Yang; Wang, Si-Yao; Peng, Cheng; Yang, Ling-Ling; Wang, Zhou-Yu; Wu, Yong; Qian, Shan; Li, Guo-Bo [Journal of Medicinal Chemistry, 2021, vol. 64, # 12, p. 8303 - 8332]

9
[ 2577-48-2 ]
[ 16947-84-5 ]
(S)-1-((S)-2-Benzyloxycarbonylamino-3-tert-butoxycarbonylamino-propionyl)-pyrrolidine-2-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1992,vol. 114,p. 6570 - 6571
[2]Organic letters,1999,vol. 1,p. 1225 - 1228

10
[ 59936-29-7 ]
[ 2577-48-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogenchloride In 1,4-dioxane
95%	With aluminium chloride anhydrous In dichloromethane for 1.5h; Ambient temperature;
90%	With stannous trifluoromethanesulfonate In dichloromethane at 20℃; for 2h;

	With hydrogenchloride In 1,4-dioxane
	With trifluoroacetic acid In dichloromethane at 20℃; for 1h;
	With trifluoroacetic acid
	With trifluoroacetic acid In dichloromethane at 20℃; for 1.5h;
	With hydrogenchloride	Phenyl ester of L-proline (Ph-O-L-proline): General procedure: Phenol (200 mg, 2 mmol) and boc-L-proline (440 mg, 2 mmol) were dissolved in 8 mL dry dichloromethane under inert atmosphere conditions. The solution of EDC (360 mg, 2.1 mmol) in dry dichloromethane was then added dropwise in the above solution. The reaction was allowed to stir for 3 h. After the completion, 1 N HCl solution was added to the reaction and extracted with dichloromethane. The dichloromethane was removed under reduced pressure [28-31]. The obtained product was then treated with 1 N HCl solution in order to deprotect Boc-group and then extracted with dichloromethane [32,33]. The dried solid product was characterized with spectroscopic techniques as given below. A similar approach was used to prepare phenyl amide (Ph-N-L-proline) and methyl ester of L-proline (CH3-O-Lproline) by using aniline and methanol, respectively instead of phenol. The structures of the prepared L-proline derivatives are shown in Fig. 1.
	With trifluoroacetic acid In dichloromethane

Reference： [1]Paruszewski; Jaworski; Tautt; Dudkiewicz [Pharmazie, 1997, vol. 52, # 3, p. 206 - 209]
[2]Bose, D. Subhas; Lakshminarayana, V. [Synthesis, 1999, # 1, p. 66 - 68]
[3]Bose, D. Subhas; Kumar, K. Kiran; Reddy, A.V. Narsimha [Synthetic Communications, 2003, vol. 33, # 3, p. 445 - 450]
[4]Unkovskii, V. I.; Vasil'eva, G. A.; Evstigneeva, R. P. [Journal of general chemistry of the USSR, 1986, vol. 56, p. 1455 - 1460][Zhurnal Obshchei Khimii, 1986, vol. 56, # 7, p. 1641 - 1647]
[5]Vendeville, Sandrine; Goossens, Filip; Debreu-Fontaine, Marie-Ange; Landry, Valérie; Davioud-Charvet, Elisabeth; Grellier, Philippe; Scharpe, Simon; Sergheraert, Christian [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 6, p. 1719 - 1729]
[6]Varela, Michael C.; Dixon, Seth M.; Price, Michael D.; Merit, Jeffrey E.; Berget, Patrick E.; Shiraki, Saori; Kurth, Mark J.; Schore, Neil E. [Tetrahedron, 2007, vol. 63, # 16, p. 3334 - 3339]
[7]Shoji, Takao; Kim, Shokaku; Yamamoto, Keisuke; Kawai, Tomomitsu; Okada, Yohei; Chiba, Kazuhiro [Organic Letters, 2014, vol. 16, # 24, p. 6404 - 6407]
[8]Ahmed, T. I.; Alwera, S.; Alwera, V.; Jaishetty, N.; Sehlangia, S.; Talismanov, V. S. [Asian Journal of Chemistry, 2022, vol. 34, # 5, p. 1213 - 1319]
[9]Mishra, Ashutosh Kumar; Mouli, M S S Vinod [Journal of Chemical Sciences, 2022, vol. 134, # 2]

11
[ 43041-12-9 ]
[ 2577-48-2 ]

Reference： [1]Tetrahedron,2004,vol. 60,p. 671 - 677
[2]Chemistry Letters,1982,p. 745 - 748

12
[ 2577-48-2 ]
[ 501-53-1 ]
[ 5211-23-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; water;	STR18 180 g (1.01 mol) of benzyl chloroformate are added dropwise to a solution of 130 g (1 mol) of S-proline methyl ester and 155 ml (1.1 mol) of triethylamine in 600 ml of absolute tetrahydrofuran at a temperature between 0 C. and 10 C., while stirring, a colorless precipitate separating out. The reaction mixture is left to stand at room temperature for 16 hours and is then poured into 1.5 liters of water. The resulting mixture is extracted several times with ethyl acetate. The combined organic phases are washed first with dilute aqueous hydrochloric acid and then with water and are concentrated under reduced pressure. The residue which remains is distilled under a high vacuum. 188 g (72% of theory) of N-benzyloxycarbonyl-S-proline methyl ester of boiling point 160 C./0.1 mbar are obtained in this manner.

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2000,p. 3264 - 3266
[2]Chemistry of Heterocyclic Compounds,1993,vol. 29,p. 1347 - 1351
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 1561 - 1566
[3]Tetrahedron Letters,2001,vol. 42,p. 4013 - 4016
[4]Patent: US4808725,1989,A
[5]Heterocycles,2019,vol. 99,p. 604 - 613

13
[ 186581-53-3 ]
[ 147-85-3 ]
[ 2577-48-2 ]
[ 27957-91-1 ]

Reference： [1]Heteroatom Chemistry,2017,vol. 28
[2]Russian Journal of General Chemistry,1993,vol. 63,p. 1410 - 1413
Zhurnal Obshchei Khimii,1993,vol. 63,p. 2020 - 2025

14
[ 5424-01-1 ]
[ 2577-48-2 ]
[ 174198-30-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	With diethyl cyanophosphonate; triethylamine In 1,2-dimethoxyethane at 0 - 25℃;

Reference： [1]Okawa, Tomohiro; Eguchi, Shoji [Tetrahedron Letters, 1996, vol. 37, # 1, p. 81 - 84]

15
[ 2577-48-2 ]
[ 16947-80-1 ]
[ 207273-93-6 ]

Yield	Reaction Conditions	Operation in experiment
65%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane

Reference： [1]Burrage, Sarah A.; Raynham, Tony; Bradley, Mark [Tetrahedron Letters, 1998, vol. 39, # 18, p. 2831 - 2834]

16
[ 6608-47-5 ]
[ 2577-48-2 ]
[ 741239-73-6 ]

Reference： [1]Synthesis,2000,p. 365 - 374

17
[ 13734-34-4 ]
[ 2577-48-2 ]
[ 38017-89-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: <i>N</i>-<i>tert</i>-butoxycarbonyl-<i>L</i>-phenylalanine With 1-hydroxy-7-aza-benzotriazole; 1,2-dichloro-ethane; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.0833333h; Inert atmosphere; Glovebox; Sealed tube; Stage #2: methyl (2S)-pyrrolidine carboxylate In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere; Glovebox; Sealed tube;
79%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 24h;	N-(tert-Butoxycarbonyl)-L-phenylalanyl-L-pro-line methyl ester (5). A solution of 26.52 g (100 mmol) of N-(tert-butoxycarbonyl)-L-phenylala-nine in 150 mL of THF was cooled to 0°C, and a solution of 20.6 g (100 mmol) of N,N′-dicyclohexyl-carbodiimide in 200 mL of THF and a solution of 12.91 g (100 mmol) of L-proline methyl ester in 100 mL of THF were added in succession with vigor-ous stirring. The mixture was allowed to warm up to room temperature and stirred for 24 h. The precipitate was filtered off, the solvent was removed from the filtrate under reduced pressure, and the residue was extracted with acetone. The extract was filtered and evaporated under reduced pressure, the residue was washed with hexane and reprecipitated from methylene chloride with hexane, and the oily material was separated and dried under reduced pressure until constant weight. Yield 29.74 g (79%), [α] D20 = -48.6° (c = 2.2, MeOH). IR spectrum, ν, cm -1 : 1749, 1711, 1648 (C=O), 1521 (δ NH, amide). 1 H NMR spectrum (CD 3 OD), δ, ppm: 1.38 s (9H, t-Bu), 1.80-2.00 m (3H, CH, CH 2 ), 2.78-2.86 m (1H, CH), 3.01-3.08 m (1H, CH), 3.32-3.39 m (1H, CH), 3.67 s (3H, CH 3 ), 3.69-3.77 m (1H, CH), 4.40-4.47 m (1H, CH), 4.55 t (1H, CH, J = 7.0 Hz), 7.20 d (2H, H arom , J = 8.3 Hz), 7.25-7.33 m (3H, H arom ). 13 C NMR spectrum (CD 3 OD), δ C , ppm: 25.75, 28.69, 29.89, 38.71, 48.07, 52.62, 55.00, 60.37, 80.38, 127.65, 129.32, 130.54, 138.22, 157.35, 172.73, 173.73. Found, %: C 64.02; H 7.84; N 7.19. C 20 H 28 N 2 O 5 . Calculated, %: C 63.81; H 7.50; N 7.44.
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide

	With dmap; benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h; Cooling with ice;
	With dmap; dicyclohexyl-carbodiimide In dichloromethane for 1h; Inert atmosphere;
	With 4-methyl-morpholine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane

Reference： [1]Hopkins, Brett A.; Smith, Graham F.; Sciammetta, Nunzio [Organic Letters, 2016, vol. 18, # 16, p. 4072 - 4075]
[2]Gaidukevich; Rudenkova; Popova; Nikolaevich; Knizhnikov [Russian Journal of Organic Chemistry, 2018, vol. 54, # 10, p. 1562 - 1564][Zh. Org. Khim., 2018, vol. 54, # 10, p. 1549 - 1551,3]
[3]Sugawara, Masae; Tonan, Kenji; Ikawa, Shun-Ichi [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2001, vol. 57, # 6, p. 1305 - 1316]
[4]Cain, James P.; Mayorov, Alexander V.; Cai, Minying; Wang, Hui; Tan, Bahar; Chandler, Kevin; Lee, YeonSun; Petrov, Ravil R.; Trivedi, Dev; Hruby, Victor J. [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 20, p. 5462 - 5467]
[5]Location in patent: experimental part Mitra, Rajendra Narayan; Shome, Anshupriya; Paul, Pritha; Das, Prasanta Kumar [Organic and Biomolecular Chemistry, 2009, vol. 7, # 1, p. 94 - 102]
[6]Kang, Seock Yong; Park, Yong Sun [European Journal of Organic Chemistry, 2012, # 9, p. 1703 - 1706]
[7]Domzalski, Alison; Margent, Liliana; Vigo, Valeria; Dewan, Faizunnahar; Pilarsetty, Naga Vara Kishore; Xu, Yujia; Kawamura, Akira [Molecules, 2021, vol. 26, # 19]

18
[ 89942-77-8 ]
[ 2577-48-2 ]
9-hydroxy-1,2,3,11a-tetrahydro-10H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11-dione [ No CAS ]