Name: 21062-20-4|2,2-Oxydiacetylchloride|97%
Brand: Ambeed
SKU: A339483
Rating: 90 (22 reviews)

1
[ 110-99-6 ]
[ 21062-20-4 ]

Yield	Reaction Conditions	Operation in experiment
86.2%	With thionyl chloride; for 5h;Reflux;	A solution of diglycolic acid (100 grams, 745.76 mmol) and thionyl chloride (125 ml, 1.713 mol) was refluxed for 5 hours. Excess thionyl chloride was distilled off and the acid chloride was purified by high vacuum distillation to get pure product 25 (110 grams, 86.2%) as a light yellow liquid. bp: 84-87 C./2 mm Hg.
78.6%	With thionyl chloride; for 5h;Reflux;	Diglycolyl Chloride A solution of diglycolic acid (25 grams, 186.44 mmol) and Thionyl chloride (30 mL, 411.17) was refluxed for 5 hours. Excess thionyl chloride was distilled off and the acid chloride was purified by high vacuum distillation to get pure product (25 grams, 78.6%) as a light yellow liquid. bp: 84-87 C./2 mm Hg.
	With thionyl chloride;	Diglycolyl Chloride A solution of diglycolic acid (25 grams, 186.44 mmol) and Thionyl chloride (30 mL, 411.17) was refluxed for 5 hours. Excess thionyl chloride was distilled off and the acid chloride was purified by high vacuum distillation to get pure product (25 grams, 78.6%) as a light yellow liquid. bp: 84-87 C./2 mm Hg.

	With thionyl chloride; at 20 - 85℃; for 5h;Reflux;	Compound 104Diglycolic acid (25 g) was added to a dry flask. To this was added thionyl chloride (85 mL) and the reaction was immediately heated to reflux and stirred at this temperature for 5 hours. At this time, the excess thionyl chloride was distilled at 85C and reduced pressure, followed by high vacuum at room temperature until mixture precipitated. Then the crude sludge was distilled at 40C under high vacuum and increasing temperature until all liquid was collected.
	With thionyl chloride; In ethyl acetate; at 0℃; for 7.5h;Inert atmosphere; Reflux;	General procedure: Thionyl chloride (6.52 mL, 90 mmol) was added slowly toa solution of 2, 20-<strong>[110-99-6]oxydiacetic acid</strong> (2.01 g, 15 mmol) inethyl acetate (30 mL) at 0-5 C under nitrogen atmosphere. The reaction mixture was stirred for 30 min at0-5 C and at room temperature for the same durationfollowed by refluxing along with stirring at 70 C over aperiod of 7 h. The highly hygroscopic and reactive compound(2, 20-oxydiacetyl chloride) yielded by concentratingthe solution under reduced pressure (Scheme 1). Both 2, 20-oxydiacetyl chloride (2 g, 11.6 mmol) and 1,5-diamino-3-aza-pentane (1.29 mL, 12 mmol) were diluted by addingdry THF (120 mL) separately and added drop wisesimultaneously by dropping funnels to ice cooled dry THF(350 mL) under nitrogen-atmosphere. During drop wiseaddition of these reactants, triethylamine (5.02 mL,36 mmol) was added to catalyze the reaction. The reactionmixture was stirred at 0-5 C followed by overnight stirringat room temperature. Progress of reaction was monitoredby TLC. Solvent was removed under reducedpressure to yield the macrocyclic product OTDD, whichwas purified by washing with chloroform (5 mL) 8-10times followed by etheration and vacuum drying to yieldthe pure compound (Fig. 1).
	With thionyl chloride; In dichloromethane; at 20 - 70℃;	Di-, tri- or tetra-carboxylic acids (1 eq.) and CH2CI2(0.114 M concentration) were added to a two-dram vial. SOCl2(15 eq. per carboxylic acid) was then added and the reaction mixture was left to stir for four hours at room temperature (some substrates required heating at 70 C overnight for full solution and/or conversion). The solvent was removed via N2flow. The residue was dissolved in 3 mL of dry CH2CI2which was then removed under N2flow. This process was performed two additional times in an attempt to remove any free HCl from the sample. The resulting residue was then used without purification in the dimerization reaction.
	With thionyl chloride; for 3h;Reflux;	(1) 134 g of diglycolic acid and476 g of thionyl chloride was added to the round bottom flask.Reflux for 3 hours. After the reaction, the excess thionyl chloride was removed by distillation under reduced pressure.A diglycolyl chloride is obtained.

Reference： [1]Tetrahedron Letters,1989,vol. 30,p. 1369 - 1372
[2]RSC Advances,2015,vol. 5,p. 103782 - 103789
[3]Patent: US2012/197037,2012,A1 .Location in patent: Page/Page column 37
[4]Patent: US8053591,2011,B2 .Location in patent: Page/Page column 62
[5]Liebigs Annalen der Chemie,1991,p. 1083 - 1084
[6]Journal of the American Chemical Society,1986,vol. 108,p. 2989 - 2998
[7]Justus Liebigs Annalen der Chemie,1893,vol. 273,p. 66
[8]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 297 - 302
[9]Journal of the American Chemical Society,1990,vol. 112,p. 9586 - 9590
[10]Tetrahedron,1982,vol. 38,p. 2055 - 2060
[11]Journal of the American Chemical Society,1985,vol. 107,p. 3981
[12]Helvetica Chimica Acta,1980,vol. 63,p. 191 - 196
[13]Journal of the Chemical Society. Perkin transactions II,1991,p. 1261 - 1266
[14]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 5316 - 5321
[15]Patent: US2009/105352,2009,A1
[16]Journal of Chemical and Engineering Data,2009,vol. 54,p. 102 - 107
[17]Journal of Chemical and Engineering Data,2008,vol. 53,p. 2189 - 2192
[18]Patent: WO2012/40204,2012,A2 .Location in patent: Page/Page column 27
[19]Journal of Inclusion Phenomena and Macrocyclic Chemistry,2015,vol. 83,p. 299 - 307
[20]Chemical Biology and Drug Design,2016,vol. 87,p. 730 - 736
[21]Patent: WO2018/85921,2018,A1 .Location in patent: Page/Page column 29; 30
[22]Patent: CN109824532,2019,A .Location in patent: Paragraph 0026; 0027; 0030; 0031; 0034; 0035

2
[ 100-02-7 ]
[ 21062-20-4 ]
[ 56173-23-0 ]

Yield	Reaction Conditions	Operation in experiment
55.9%	With triethylamine In acetone at 4 - 20℃;	1.B.2 Synthesis of di~p-nitrophenyl ester of diglycolic acid; The following exemplary procedure illustrates synthesis of di-p-nitrophenyl ester of diglycolic acid. Triethylamine (61.6 mL, 0.442 mol) was added to a stirring solution of p-nitrophenol (61.5 g, 0.442 mol) in dry acetone (350 mL). The solution was cooled down to 4°C and digJycolyl chloride (25 mL, 0.21 mol) was added drop-wise to the solution over 30 min under argon. Then the cooling bath was removed and stirring was continued overnight at room temperature. The reaction mixture was diluted with water (450 mL) and stirred for 10 min. The resultant solid was collected by filtration and washed, first with 0.1 N HCl water solution (500 mL) and then with water (500 mL). The resulting di-ester was recrystallized in acetone and then dried at 60 0C under vacuum for 20 h to obtain 32.8 g of product. The filtrate was kept at 4 0C for three days to obtain an additional 11.4 g of product. The combined total yield was 44.2 g (55.9%) with mp 166.8 0C, lit. 166-167 0C (Zimmer, H et al., /. Org. Chem. (1975) 40:2901-06). 1H NMR (DMSO-c?6): δ = 4.68 (s, 4H), 7.52 (d, J= 7.2 Hz, 4H), 8.34 (d, J= 7.2 Hz, 4H).
	With pyridine In hexane; chloroform; water; ethyl acetate	26 Example-26 Example-26 (4-Nitro-phenoxycarbonylmethoxy)-acetic acid 4-nitro-phenyl ester To a solution of 4-nitrophenol (81.35 grams, 584.78 mmol) and pyridine (47.3 ml, 584.82 mmol) in chloroform at 0° C. under N2 atmosphere was added diglycolyl chloride 25 (50 grams, 292.43 mmol) drop wise. Further stirred at 0° C. for 8 hours, filtered the separated solid, and discarded the chloroform layer which continued unreacted 4-Nitrophenol along with some product. The filtered solid was taken into water (2000 ml), extracted with ethyl acetate (3300 ml), the combined ethyl acetate layer washed with 5% sodium bicarbonate (3300 ml), water (1*300 ml), dried over sodium sulphate, distilled off 80% ethyl acetate and to the residue added hexane (250 ml), filtered the precipitated product to get dinitro compound 26 (60 grams) as white powder. mp: 161.8-163.6° C., Mass: M+Na=399. The pure product 26 was also characterized using 1H NMR spectroscopy in DMSO-d6: δ 4.64(s, 2H, CH2), 7.42 (d, 2H, Ar), 8.36 (d, 4H, Ar).
	With pyridine In chloroform at 0℃; for 8h; Inert atmosphere;	26 To a solution of 4-nitrophenol (81.35 grams, 584.78 mmol) and pyridine (47.3 ml, 584.82 mmol) in chloroform at 0° C. under N2 atmosphere was added diglycolyl chloride 25 (50 grams, 292.43 mmol) drop wise. Further stirred at 0° C. for 8 hours, filtered the separated solid, and discarded the chloroform layer which continued unreacted 4-Nitrophenol along with some product. The filtered solid was taken into water (2000 ml), extracted with ethyl acetate (3×300 ml), the combined ethyl acetate layer washed with 5% sodium bicarbonate (3×300 ml), water (1×300 ml), dried over sodium sulphate, distilled off 80% ethyl acetate and to the residue added hexane (250 ml), filtered the precipitated product to get dinitro compound 26 (60 grams) as white powder. mp: 161.8-163.6° C., Mass: M+Na=399. The pure product 26 was also characterized using 1H NMR spectroscopy in DMSO-d6: δ 4.64 (s, 2H, CH2), 7.42 (d, 2H, Ar), 8.36 (d, 4H, Ar).

With alkaline solution

Reference： [1]Current Patent Assignee: MEDIVAS - WO2007/133616, 2007, A2 Location in patent: Page/Page column 45
[2]Current Patent Assignee: BEZWADA BIOMEDICAL; BEZWADA BIOMEDICAL LLC - US2009/82540, 2009, A1
[3]Current Patent Assignee: BEZWADA BIOMEDICAL; BEZWADA BIOMEDICAL LLC - US2012/197037, 2012, A1 Location in patent: Page/Page column 37
[4]Current Patent Assignee: Boehringer & Soehne - DE223305, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1086,1087][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1086,1087]

3
[ 21062-20-4 ]
[ 3119-15-1 ]
[ 2618-25-9 ]

Reference： [1]Chemische Berichte,1954,vol. 87,p. 651,652

4
[ 21062-20-4 ]
[ 69-72-7 ]
[ 846589-01-3 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran at 20℃; for 0.5h;	1 To a stirred solution of 40.80 g of salicylic acid (0.296 mol) and 24 mL of anhydrous pyridine in 300 mL of anhydrous THF was added 24.8g of diglycolyl chloride (0.145 mol) dissolved in 50 mL of anhydrous THF in a slow, drop-wise fashion. A white precipitate was formed during the addition. The reaction mixture was stirred at ambient temperature for an additional 30 minutes. The reaction mixture was poured into 2 L of ice-water containing 25 mL of cone. HCl. After stirring for 15 minutes, the white solid was filtered, and washed with water until the washings were neutral to pH paper. The product was dried overnight in a vacuum oven at 400C. After drying, the crude product was twice suspended in 300 mL of hexane/ethyl acetate (75:25 v/v), stirred for 30 minutes and filtered. The product was dried overnight in a vacuum oven at 40 0C. Isolated yield was 5 Ig. 1H NMR (CDCl3) δ: 8.05 (dd, 2H, J = 1.8 and 7.5 Hz), 7.53 (m, 2H), 7.32 (m, 2H), 7.15 (dd, 2H, H = 1.8, 7.5 Hz), 6.84 (bs, 2H, exchanged with D2O), 4.63 (s, 4H). 13C NMR (DMSO-J6) δ: 169.2, 166.2, 150.3, 134.7, 132.3, 127.2, 124.4, 68.4.
	With 2,3-Dimethylaniline; benzene

Reference： [1]Current Patent Assignee: POLYMERIX - WO2008/34019, 2008, A2 Location in patent: Page/Page column 28-29
[2]Current Patent Assignee: Boehringer & Soehne - DE223305, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1086,1087][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1086,1087]

5
[ 67-56-1 ]
[ 21062-20-4 ]
[ 7040-23-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine at 0 - 20℃;
80%	With pyridine In benzene for 6h; Reflux; Inert atmosphere;
80%	With pyridine In benzene at 20℃; for 30h; Inert atmosphere; Reflux;	3.4. Synthesis of dimethyloxalate and dimethyldiglycolate General procedure: The synthetic procedures described in the literature33 were applied for the preparation of these esters. To amixture of methanol and pyridine in 500 mL with ux under dry nitrogen, a solution of oxalylchloride (38.0g, 300 mmol) or diglycolic acid dichloride (17.1 g, 100 mmol) in benzene (250 mL) was added drop-wise via apressure-controlled dropping funnel for a period of 3 h. The solution was reuxed for 3 h and then kept stirringfor 24 h at room temperature. The precipitated salt was removed by ltration and the solvent was removedby evaporation in vacuum. The remaining residue was extracted with ice-cold ether (3 50 mL), producing awhite solid after evaporation. The products were recrystallized from diethyl ether-petroleum ether (2:1). Mp:54{54.5 C, yield: 92% for oxalate ester; mp: 36{37.5 C, yield: 80% for diglycolate ester.

	With pyridine
	Multistep reaction;

Reference： [1]Alfonso, Ignacio; Rebolledo, Francisca; Gotor, Vicente [Chemistry - A European Journal, 2000, vol. 6, # 18, p. 3331 - 3338]
[2]Location in patent: experimental part Baris, Deniz; Seker, Sevil; Hosgoeren, Halil; Togrul, Mahmut [Tetrahedron Asymmetry, 2010, vol. 21, # 15, p. 1893 - 1899]
[3]Çolak, Mehmet; Bariş, Deniz; Pirinççioǧlu, Necmettin; Hoşgören, Halil [Turkish Journal of Chemistry, 2017, vol. 41, # 5, p. 658 - 671]
[4]Rasshofer,W. et al. [Chemische Berichte, 1979, vol. 112, p. 2095 - 2119]
[5]Roelens, Stefano [Journal of the Chemical Society. Perkin transactions II, 1988, p. 1617 - 1626]

6
[ 2752-17-2 ]
[ 21062-20-4 ]
[ 31249-98-6 ]

Yield	Reaction Conditions	Operation in experiment
60%	In benzene at 25℃; for 0.333333h;
15.5 g (58%)	In benzene	1 EXAMPLE 1 EXAMPLE 1 Following the reaction scheme STR17 a solution (500 ml) of 2,2-oxybis(acetyl chloride) (2) (24.5 g, 0.14 mole) in anhydrous benzene and a solution (500 ml) of 1,5-diamino-3-oxapentane (3) (30.0 g, 0.28 mole) in anhydrous benzene were added simultaneously to 1 liter of violently stirred anhydrous benzene at a rate of 2.5 ml per minute at room temperature. The precipitate was filtered and washed with hot CHCl3, and the filtrates were evaporated to give a residue which was recrystallized from chloroform-heptane to afford 15.5 g (58%) of 5,9-dioxo-1,7-dioxa-4,10-diazacyclododecane, mp 169°-171° C.

Reference： [1]Cram, Donald J.; Ho, Siew Peng; Knobler, Carolyn B.; Maverick, Emily; Trueblood, Kenneth N. [Journal of the American Chemical Society, 1986, vol. 108, # 11, p. 2989 - 2998]
[2]Dietrich,B. et al. [Tetrahedron, 1973, vol. 29, p. 1629 - 1645]
[3]Current Patent Assignee: BAYER AG - US4900818, 1990, A

7
[ 6850-57-3 ]
[ 21062-20-4 ]
[ 105399-90-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine In benzene for 1h; Ambient temperature;
	With triethylamine In benzene at 0 - 8℃;

Reference： [1]Gatto, Vincent J.; Arnold, Kristin A.; Viscariello, Anthony M.; Miller, Steven R.; Morgan, Charles R.; Gokel, George W. [Journal of Organic Chemistry, 1986, vol. 51, # 26, p. 5373 - 5384]
[2]Gatto, Vincent J.; Arnold, Kristin A.; Viscariello, Anthony M.; Miller, Steven R.; Gokel, George W. [Tetrahedron Letters, 1986, vol. 27, # 3, p. 327 - 330]

8
[ 617-89-0 ]
[ 21062-20-4 ]
[ 105399-93-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine In benzene for 1h; Ambient temperature;
	With triethylamine In benzene at 0 - 8℃;

Reference： [1]Gatto, Vincent J.; Arnold, Kristin A.; Viscariello, Anthony M.; Miller, Steven R.; Morgan, Charles R.; Gokel, George W. [Journal of Organic Chemistry, 1986, vol. 51, # 26, p. 5373 - 5384]
[2]Gatto, Vincent J.; Arnold, Kristin A.; Viscariello, Anthony M.; Miller, Steven R.; Gokel, George W. [Tetrahedron Letters, 1986, vol. 27, # 3, p. 327 - 330]

9
[ 17431-03-7 ]
[ 21062-20-4 ]
[ 96746-89-3 ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine In diethyl ether

Reference： [1]Talma,A.G.; Jouin,P.; De Vries,J.G. [Journal of the American Chemical Society, 1985, vol. 107, p. 3981]

10
[ 7249-78-7 ]
[ 21062-20-4 ]
[ 73776-07-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	With pyridine In 1,4-dioxane; benzene at 75℃; for 6h;
40%	With pyridine In benzene at 20℃; for 24h;

Reference： [1]Formanovskii, A. A.; Mikhura, I. V.; Sokolovskii, S. A.; Murakhovskaya, A. S.; Terent'ev, P. B.; Sharbatyan, P. A. [Chemistry of Heterocyclic Compounds, 1988, vol. 24, # 8, p. 930 - 936][Khimiya Geterotsiklicheskikh Soedinenii, 1988, # 8, p. 1128 - 1135]
[2]Markovich, I. S.; Filyagina, N. A.; Dziomko, V. M.; Ryabokobylko, Yu. S.; Adamova, G. M.; Zelichenok, S. L. [Chemistry of Heterocyclic Compounds, 1983, p. 150 - 153][Khimiya Geterotsiklicheskikh Soedinenii, 1983, vol. 19, # 2, p. 185 - 188]

11
[ 21062-20-4 ]
[ 2627-86-3 ]
[ 150723-37-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium hydroxide In tetrahydrofuran for 0.5h; Ambient temperature;

Reference： [1]Jursic, Branko S.; Goldberg, Stanley I. [Journal of Organic Chemistry, 1992, vol. 57, # 28, p. 7370 - 7372]

12
[ 21062-20-4 ]
[ 2577-90-4 ]
[ 105229-64-9 ]

Yield	Reaction Conditions	Operation in experiment
68%	With triethylamine In dichloromethane
	With triethylamine In dichloromethane

Reference： [1]Vriesema, Bindert K.; Lemaire, Marc; Buter, Jan; Kellogg, Richard M. [Journal of Organic Chemistry, 1986, vol. 51, # 26, p. 5169 - 5177]
[2]Lemaire, Marc; Vrisema, Bindert K.; Kellogg, Richard M. [Tetrahedron Letters, 1985, vol. 26, # 29, p. 3499 - 3502]

13
[ 21062-20-4 ]
[ 52411-34-4 ]
[ 96656-69-8 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1985,vol. 21,p. 225 - 229
Khimiya Geterotsiklicheskikh Soedinenii,1985,vol. 21,p. 267 - 271

14
[ 21062-20-4 ]
[ 52411-33-3 ]
[ 96656-72-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine In benzene at 75℃; for 3h; simultaneous addition during 6 h;

Reference： [1]Formanovski, A. A.; Murakhovskaya, A. S. [Chemistry of Heterocyclic Compounds, 1985, vol. 21, # 2, p. 225 - 229][Khimiya Geterotsiklicheskikh Soedinenii, 1985, vol. 21, # 2, p. 267 - 271]

15
[ 21062-20-4 ]
[ 54533-68-5 ]
[ 120340-68-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With pyridine In 1,4-dioxane; benzene at 75℃; for 6h;

Reference： [1]Formanovskii, A. A.; Mikhura, I. V.; Sokolovskii, S. A.; Murakhovskaya, A. S.; Terent'ev, P. B.; Sharbatyan, P. A. [Chemistry of Heterocyclic Compounds, 1988, vol. 24, # 8, p. 930 - 936][Khimiya Geterotsiklicheskikh Soedinenii, 1988, # 8, p. 1128 - 1135]

16
[ 21062-20-4 ]
[ 109093-57-4 ]
[ 120340-64-9 ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine In 1,4-dioxane; benzene at 75℃; for 6h;

Reference： [1]Formanovskii, A. A.; Mikhura, I. V.; Sokolovskii, S. A.; Murakhovskaya, A. S.; Terent'ev, P. B.; Sharbatyan, P. A. [Chemistry of Heterocyclic Compounds, 1988, vol. 24, # 8, p. 930 - 936][Khimiya Geterotsiklicheskikh Soedinenii, 1988, # 8, p. 1128 - 1135]

17
[ 21062-20-4 ]
[ 147688-25-3 ]
[ 147688-26-4 ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethylamine In toluene at 60℃; for 15h;

Reference： [1]Zinic, Mladen; Alihodzic, Sulejman; Skaric, Vinko [Journal of the Chemical Society. Perkin transactions I, 1993, # 1, p. 21 - 26]

18
[ 21062-20-4 ]
[ 134918-24-4 ]
Acetic acid 14,18-dioxo-2,6,16-trioxa-13,19-diaza-tricyclo[18.4.0.0^7,12]tetracosa-1⁽²⁴⁾,7⁽¹²⁾,8,10,20,22-hexaen-4-yl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine In benzene at 75℃;

Reference： [1]Formanovskii, A. A.; Mikhura, I. V. [Chemistry of Heterocyclic Compounds, 1991, vol. 27, # 2, p. 227 - 231][Khimiya Geterotsiklicheskikh Soedinenii, 1991, # 2, p. 275 - 279]

19
[ 21062-20-4 ]
[ 111-92-2 ]
N,N,N,N-tetrabutyl-3-oxapentane-diamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In dichloromethane for 10h; Ambient temperature;
89%	With sodium hydroxide In diethyl ether; water monomer at 0 - 5℃; for 2.5h;	General Procedure 1: Synthesis of Diglycolamides by Schotten-Baumann Reaction General procedure: Diglycolyl chloride (0.85 g, 5 mmol) in Et2O (30 mL) was added dropwise to a solution of amine (30 mmol) and NaOH (1.2 g, 30mmol) in water (36 mL) at 0 °C over 30 min. The mixture was stirred at 0 °C for 2 h, and then the phases were separated. The aqueous layer was saturated with NaCl and extracted with Et2O (3 × 30 mL). An aqueous solution of 10 % HCl (20 mL) was added to the combined organic layers. The mixture was shaken vigorously to facilitate formation of clumps of ammonium salts, floating between the two phases. The organic layer was washed two more times with HCl solution (20 mL) and then filtered through a glass frit (G3). A poly(4-styrenesulfonic acid) solution (4 wt%, 25 mL) in water was added to the organic layer. The mixture was shaken vigorously to facilitate formation of polymeric salts as an amorphous material floating between the layers. The organic layer was washed with water and then separated from the polymeric salt. It was dried with MgSO4, where upon the solvent was removed by vacuum evaporation to afford the DGAs, which had a purity of ≥97 % according to the 1H NMR spectra.
	In dichloromethane at 20℃; Inert atmosphere;

With triethylamine In tetrahydrofuran

1. Synthesis of tetraalkyl diglycolamide General procedure: N,N,N,N-tetraalkyl diglycolamide (Fig. S1) was synthesized by reacting diglycolyl chloride with respective dialkyl amine as per the following reaction. The reaction was carried out in THF in the presence of triethylamine. The products were washed with distilled water and dilute HCl to remove un-reacted diglycolyl chloride and dialkyl amine, respectively. Final product was purified by column chromatography. The materials were characterized by 1H-NMR (Fig. S2) and FT-IR (Fig. S3).

Reference： [1]Skinner; Rosentreter; Elward [Journal of Pharmaceutical Sciences, 1982, vol. 71, # 7, p. 837 - 839]
[2]Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem [Synlett, 2016, vol. 27, # 17, p. 2463 - 2466]
[3]Location in patent: experimental part Liu, Jiang-Fan; Yang, Hai-Jian; Wang, Wei; Li, Zhongxiao [Journal of Chemical and Engineering Data, 2008, vol. 53, # 9, p. 2189 - 2192]
[4]Ansari, Seraj A.; Dumpala, Rama Mohana R.; Mohapatra, Prasanta K.; Verboom, Willem [Polyhedron, 2022, vol. 220]

20
[ 21062-20-4 ]
[ 109-89-7 ]
[ 77077-06-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	In dichloromethane for 10h; Ambient temperature;
90%	With sodium hydroxide In diethyl ether; water monomer at 0 - 5℃; for 2.5h;	General Procedure 1: Synthesis of Diglycolamides by Schotten-Baumann Reaction General procedure: Diglycolyl chloride (0.85 g, 5 mmol) in Et2O (30 mL) was added dropwise to a solution of amine (30 mmol) and NaOH (1.2 g, 30mmol) in water (36 mL) at 0 °C over 30 min. The mixture was stirred at 0 °C for 2 h, and then the phases were separated. The aqueous layer was saturated with NaCl and extracted with Et2O (3 × 30 mL). An aqueous solution of 10 % HCl (20 mL) was added to the combined organic layers. The mixture was shaken vigorously to facilitate formation of clumps of ammonium salts, floating between the two phases. The organic layer was washed two more times with HCl solution (20 mL) and then filtered through a glass frit (G3). A poly(4-styrenesulfonic acid) solution (4 wt%, 25 mL) in water was added to the organic layer. The mixture was shaken vigorously to facilitate formation of polymeric salts as an amorphous material floating between the layers. The organic layer was washed with water and then separated from the polymeric salt. It was dried with MgSO4, where upon the solvent was removed by vacuum evaporation to afford the DGAs, which had a purity of ≥97 % according to the 1H NMR spectra.
	In dichloromethane at 20℃; Inert atmosphere;

With triethylamine In tetrahydrofuran

1. Synthesis of tetraalkyl diglycolamide General procedure: N,N,N,N-tetraalkyl diglycolamide (Fig. S1) was synthesized by reacting diglycolyl chloride with respective dialkyl amine as per the following reaction. The reaction was carried out in THF in the presence of triethylamine. The products were washed with distilled water and dilute HCl to remove un-reacted diglycolyl chloride and dialkyl amine, respectively. Final product was purified by column chromatography. The materials were characterized by 1H-NMR (Fig. S2) and FT-IR (Fig. S3).

Reference： [1]Skinner; Rosentreter; Elward [Journal of Pharmaceutical Sciences, 1982, vol. 71, # 7, p. 837 - 839]
[2]Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem [Synlett, 2016, vol. 27, # 17, p. 2463 - 2466]
[3]Location in patent: experimental part Liu, Jiang-Fan; Yang, Hai-Jian; Wang, Wei; Li, Zhongxiao [Journal of Chemical and Engineering Data, 2008, vol. 53, # 9, p. 2189 - 2192]
[4]Ansari, Seraj A.; Dumpala, Rama Mohana R.; Mohapatra, Prasanta K.; Verboom, Willem [Polyhedron, 2022, vol. 220]

21
[ 21062-20-4 ]
[ 109-73-9 ]
[ 31353-28-3 ]

Yield	Reaction Conditions	Operation in experiment
65%	With triethylamine In benzene at 25℃; for 2h;
	With triethylamine In benzene at 0 - 8℃;

Reference： [1]Anelli, Pier Lucio; Lunazzi, Ludovico; Montanari, Fernando; Quici, Silvio [Journal of Organic Chemistry, 1984, vol. 49, # 22, p. 4197 - 4203]
[2]Gatto, Vincent J.; Arnold, Kristin A.; Viscariello, Anthony M.; Miller, Steven R.; Gokel, George W. [Tetrahedron Letters, 1986, vol. 27, # 3, p. 327 - 330]

22
[ 21062-20-4 ]
[ 108-18-9 ]
[ 74267-25-7 ]

Yield	Reaction Conditions	Operation in experiment
61%	With sodium hydroxide In diethyl ether; water at 0 - 5℃; for 2.5h;	General Procedure 1: Synthesis of Diglycolamides by Schotten-Baumann Reaction General procedure: Diglycolyl chloride (0.85 g, 5 mmol) in Et2O (30 mL) was added dropwise to a solution of amine (30 mmol) and NaOH (1.2 g, 30mmol) in water (36 mL) at 0 °C over 30 min. The mixture was stirred at 0 °C for 2 h, and then the phases were separated. The aqueous layer was saturated with NaCl and extracted with Et2O (3 × 30 mL). An aqueous solution of 10 % HCl (20 mL) was added to the combined organic layers. The mixture was shaken vigorously to facilitate formation of clumps of ammonium salts, floating between the two phases. The organic layer was washed two more times with HCl solution (20 mL) and then filtered through a glass frit (G3). A poly(4-styrenesulfonic acid) solution (4 wt%, 25 mL) in water was added to the organic layer. The mixture was shaken vigorously to facilitate formation of polymeric salts as an amorphous material floating between the layers. The organic layer was washed with water and then separated from the polymeric salt. It was dried with MgSO4, where upon the solvent was removed by vacuum evaporation to afford the DGAs, which had a purity of ≥97 % according to the 1H NMR spectra.
14%	In pyridine; benzene for 24h; Ambient temperature;

Reference： [1]Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem [Synlett, 2016, vol. 27, # 17, p. 2463 - 2466]
[2]Pretsch, Erno; Ammann, Daniel; Osswald, Hans F.; Guggi, Marc; Simon, Wilhelm [Helvetica Chimica Acta, 1980, vol. 63, # 1, p. 191 - 196]

23
[ 21062-20-4 ]
[ 111-42-2 ]
[ 144084-73-1 ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium carbonate In acetone at 0 - 20℃;
	With triethylamine In chloroform for 12h; Ambient temperature;

Reference： [1]Location in patent: experimental part Iqbal, Mudassir; Huskens, Jurriaan; Sypula, Michal; Modolo, Giuseppe; Verboom, Willem [New Journal of Chemistry, 2011, vol. 35, # 11, p. 2591 - 2600]
[2]Bradshaw, Jerald S.; An, Haoyun; Krakowiak, Krzysztof E.; Wang, Tingmin; Zhu, Chengyue; Izatt, Reed M. [Journal of Organic Chemistry, 1992, vol. 57, # 23, p. 6112 - 6118]

24
[ 21062-20-4 ]
[ 2835-06-5 ]
1,3-bis(((carboxyphenylmethyl)amino)carbonyl)-2-oxapropane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium hydroxide In dichloromethane at 5 - 20℃; for 0.833333h;

Reference： [1]Zinic, Mladen; Skaric, Vinko [Journal of Organic Chemistry, 1988, vol. 53, # 11, p. 2582 - 2588]

25
[ 21062-20-4 ]
[ 100-46-9 ]
[ 33051-25-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine In benzene at 0 - 8℃;
93%	With triethylamine In benzene for 1h; Ambient temperature;

Reference： [1]Gatto, Vincent J.; Arnold, Kristin A.; Viscariello, Anthony M.; Miller, Steven R.; Gokel, George W. [Tetrahedron Letters, 1986, vol. 27, # 3, p. 327 - 330]
[2]Gatto, Vincent J.; Arnold, Kristin A.; Viscariello, Anthony M.; Miller, Steven R.; Morgan, Charles R.; Gokel, George W. [Journal of Organic Chemistry, 1986, vol. 51, # 26, p. 5373 - 5384]

26
[ 21062-20-4 ]
[ 36343-05-2 ]
[ 74267-26-8 ]

Reference： [1]Helvetica Chimica Acta,1980,vol. 63,p. 191 - 196

27
[ 21062-20-4 ]
[ 66943-05-3 ]
2-[2-Oxo-2-(1,4,7,10-tetraoxa-13-aza-cyclopentadec-13-yl)-ethoxy]-1-(1,4,7,10-tetraoxa-13-aza-cyclopentadec-13-yl)-ethanone [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1988,p. 719 - 724

28
[ 21062-20-4 ]
[ 157947-74-5 ]
5,11,16,22-Tetrahydro-8,19-dioxa-5,11,16,22-tetraaza-dibenzo[a,j]cyclooctadecene-6,10,17,21-tetraone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With triethylamine In tetrahydrofuran at 60℃;

Reference： [1]Arnaud, Nathalie; Picard, Claude; Cazaux, Louis; Tisnes, Pierre [Tetrahedron Letters, 1995, vol. 36, # 31, p. 5531 - 5534]

29
[ 21062-20-4 ]
[ 157947-75-6 ]
5,18,21-Trioxa-2,8,15,24-tetraaza-tricyclo[23.4.0.0^9,14]nonacosa-1⁽²⁵⁾,9⁽¹⁴⁾,10,12,26,28-hexaene-3,7,16,23-tetraone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With triethylamine In tetrahydrofuran at 60℃;

Reference： [1]Arnaud, Nathalie; Picard, Claude; Cazaux, Louis; Tisnes, Pierre [Tetrahedron Letters, 1995, vol. 36, # 31, p. 5531 - 5534]

30
[ 21062-20-4 ]
[ 497968-92-0 ]
[ 497968-93-1 ]

Yield	Reaction Conditions	Operation in experiment
67%	With pyridine In benzene at 75℃; for 12h;
	With pyridine In benzene
	With pyridine In benzene at 75℃;	Compound 107Compounds 103 (17 mmol) and 104 (80 mol%, used 22 mmol) were dissolved separately in flasks with benzene ( 150 mL in each). These were concurrently added at equal rate, over several hours, to a flask containing benzene ( 150 mL) and pyridine (46 mmol). After addition was complete, placed flask in oil bath at 75°C to stir overnight. Then evaporated the benzene completely and dissolved residue in dichloromethane. Washed twice with 1 HCI mixed with some brine, then with sodium bicarbonate, and finally with brine, then dried over sodium sulfate. After evaporation under vacuum, purified by column chromatography, loading with chloroform and using 5% methanol in chloroform and increasing methanol content.

Reference： [1]Gunnlaugsson, Thorfinnur; Gunaratne, H. Q. Nimal; Nieuwenhuyzen, Mark; Leonard, Joseph P. [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2002, # 17, p. 1954 - 1962]
[2]De Silva, A. Prasanna; Gunaratne, H. Q. Nimal; Gunnlaugsson, Thorfinnur; Nieuwenhuizen, Mark [Chemical Communications, 1996, # 16, p. 1967 - 1968]
[3]Current Patent Assignee: ASANTE RES - WO2012/40204, 2012, A2 Location in patent: Page/Page column 27

31
[ 21062-20-4 ]
[ 75953-71-8 ]
[ 257890-39-4 ]

Yield	Reaction Conditions	Operation in experiment
58%	With pyridine In toluene at 20℃;

Reference： [1]Ghorbanian, Shohreh; Mehta, Lina K.; Parrick, John; Robson, Craig H. [Tetrahedron, 1999, vol. 55, # 50, p. 14467 - 14478]

32
[ 21062-20-4 ]
[ 257890-43-0 ]
4,10,16,22-tetrakis-(3-methoxy-phenyl)-1,7,13,19-tetraoxa-4,10,16,22-tetraaza-cyclotetracosane-3,11,15,23-tetraone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With pyridine In toluene at 20℃;

Reference： [1]Ghorbanian, Shohreh; Mehta, Lina K.; Parrick, John; Robson, Craig H. [Tetrahedron, 1999, vol. 55, # 50, p. 14467 - 14478]

33
[ 21062-20-4 ]
[ 536-90-3 ]
[ 257890-41-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With triethylamine In tetrahydrofuran at 0 - 20℃;

Reference： [1]Ghorbanian, Shohreh; Mehta, Lina K.; Parrick, John; Robson, Craig H. [Tetrahedron, 1999, vol. 55, # 50, p. 14467 - 14478]

34
[ 134469-06-0 ]
[ 21062-20-4 ]
[ 123845-13-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine In tetrahydrofuran at 50℃; for 2h;

Reference： [1]Picard; Arnaud; Tisnès [Synthesis, 2001, # 10, p. 1471 - 1478]

35
[ 21062-20-4 ]
[ 2491-20-5 ]
[ 599174-37-5 ]

Yield	Reaction Conditions	Operation in experiment
58%	With triethylamine In dichloromethane at 0 - 20℃;

Reference： [1]Szczepańska, Agnieszka; Sałański, Piotr; Jurczak, Janusz [Tetrahedron, 2003, vol. 59, # 26, p. 4775 - 4783]

36
[ 21062-20-4 ]
[ 115306-75-7 ]
N-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-[3-(tert-butyl-dimethyl-silanyloxy)-propylcarbamoyl]-methoxy}-acetamide [ No CAS ]

Reference： [1]Nucleosides, nucleotides and nucleic acids,2003,vol. 22,p. 1635 - 1637
[2]Bioconjugate Chemistry,2010,vol. 21,p. 1545 - 1553

37
[ 21062-20-4 ]
[ 96331-95-2 ]
[ 481666-68-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine In tetrahydrofuran for 18h;	5 Example 5. Preparation of Compound 10. To a stirred mixture of diamine Compound 9 (13.10 g, 50 MMOL) and Et3N (20.8 mL, 150 MMOL) in dry THF (2.5 L) was slowly added over 12 h a solution of diglycolyl dichloride (6.3 mL, 55 MMOL) in dry THF (0.5 L). The reaction mixture was stirred for 6 h, filtered from the precipitated hydrochloride, and washed with THF. The combined organic filtrate was evaporated. The residue was dissolved in CHCI3 (800 mL) and washed successively with 0.5 M HCI, H20, saturated NaHC03 then saturated NACI. The organic layer was dried over MGS04 AND evaporated. Ether (100 mL) was added and the precipitated product was filtered, washed with ether and dried to give Compound 10,16. 0 g (90%) as an off-white solid.
	With triethylamine In tetrahydrofuran

Reference： [1]Current Patent Assignee: THERMO FISHER SCIENTIFIC INC - WO2005/16874, 2005, A2 Location in patent: Page/Page column 56-57
[2]Martin, Vladimir V.; Rothe, Anca; Diwu, Zhenjun; Gee, Kyle R. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 21, p. 5313 - 5316]

38
[ 21062-20-4 ]
[ 83597-41-5 ]
(9S,17S)-9,17-dibenzyl-1,4,7,13-tetraoxa-10,16-diaza-cyclooctadecane-2,6,11,15-tetraone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With dmap; triethylamine In acetonitrile at 50 - 70℃; for 12h;
45%	In tetrahydrofuran; N,N-dimethyl-formamide; benzene for 120h; Reflux;

Reference： [1]Gao, Ming Zhang; Reibenspies, Joseph H.; Wang, Bo; Xu, Zun Le; Zingaro, Ralph A. [Journal of Heterocyclic Chemistry, 2004, vol. 41, # 6, p. 899 - 908]
[2]Location in patent: experimental part Baris, Deniz; Seker, Sevil; Hosgoeren, Halil; Togrul, Mahmut [Tetrahedron Asymmetry, 2010, vol. 21, # 15, p. 1893 - 1899]

39
α,α'-bis[8-(5-amino-1,3,4-thiadiazol-2-yl)-3,6-dioxapentylthio]-m-xylene [ No CAS ]
[ 21062-20-4 ]
14,15,17,23,25,26-hexaaza-6,9,20,31,34-pentaoxa-3,12,28,37,44,45-hexathiotetracyclo[37,3,1,1^13,14,1^24,27]pentatetraconta-1⁽⁴³⁾,13⁽¹⁴⁾,15⁽¹⁶⁾,24⁽²⁵⁾,26⁽²⁷⁾,39⁽⁴⁰⁾,41⁽⁴²⁾-heptaene-18,22-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.2%	With pyridine; cesium chloride In dichloromethane at 20℃; for 20h;

Reference： [1]Sook Cho, Nam; Sun Park, Mi; Hoon Kim, Young; Yu, Young-Ae; Jung Kwon, Hyun; Kim, Yeong-Joon [Heterocycles, 2006, vol. 68, # 4, p. 811 - 819]

40
[ 21062-20-4 ]
[ 22494-42-4 ]
6-bis[(2-carboxy-4(2',4'-difluorophenyl)phenyl)]glycolate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran at 20℃; for 0.5h;	5 To a solution of 10.50 g of diflunisal (0.042 mol.) and 3.7 mL of anhydrous pyridine (0.045 mol.) in 100 mL of anhydrous THF was added 3.42 g of diglycolyl chloride (0.02 mol.) in 25 mL of anhydrous THF 1 in a slow drop- wise fashion . A white precipitate was formed during the addition. The reaction mixture was stirred at ambient temperature for an additional 30 minutes. The reaction mixture was poured into 1 L of ice-water containing 5 mL of cone. HCl. After stirring for 15 minutes, the white precipitate was filtered and washed with water until the washings were neutral to pH paper. The product was dried overnight in a vacuum oven at 40 0C. After drying, the crude product was suspended in 100 mL of hexane/ethyl acetate (75:25, v/v) solvent mixture, stirred for 30 minutes, and filtered. The product was dried overnight in a vacuum oven at 40 0C. Isolated yield was H g. 1H NMR (CDCl3+DMSO-d6): 7.96 (d, 2H, J = 1.3 Hz), 7.48 (dd, 2H, J = 6.5 and 1.8 Hz), 7.26-7.02 (m, 2H), 7.0 (d, 2H, J = 8.2 Hz), 6.80-6.68 (m, 4H), 4.52 (bs, exchanged with D2O), 4.45 (s, 4H)

Reference： [1]Current Patent Assignee: POLYMERIX - WO2008/34019, 2008, A2 Location in patent: Page/Page column 32

41
[ 21062-20-4 ]
[ 846589-01-3 ]
None [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: diglycolyl chloride; 2,2'-(3-oxa-pentanedioyldioxy)-di-benzoic acid With triethylamine In dichloromethane at 0℃; for 1h; Stage #2: With bis(trichloromethyl) carbonate In dichloromethane at 0℃;	8 A solution of diglycolyl chloride (3.42 g, 0.02 mol) in anhydrous DCM (50 mL) is added to a solution of DGA bisSA diacid (7.49 g, 0.02 mol, prepared in example 1) and TEA (6.13 mL, 0.044 mol) in anhydrous DCM (30 mL) slowly at 0 0C. After the completion of the addition, the reaction solution is stirred for 1 h and diluted with DCM (100 mL). The solution is washed with IN HCl (2 x 150 mL) and distilled water (100 mL), and dried over anhydrous MgSO4. The solution is concentrated in vacuo to dryness to give the polymer. The polymer is dissolved in anhydrous DCM (100 mL) and TEA (4 equivalents ofMn of pre-polymer) is added at 0 0C. A solution of triphosgene in anhydrous DCM is added very slowly to the polymer solution at 0 0C. The addition of triphosgene is continued until the target Mw is reached by GPC (as monitored by running an aliquot through GPC). After the reaction is completed, the mixture is diluted with DCM, washed with IN HCl (2 x 150 mL) and distilled water (150 mL), and dried over anhydrous MgSO4. The solution is concentrated in vacuo till a thick oil is obtained and dropped into anhydrous diethyl ether (DCM solution-ether = 1:5, v/v) in a Teflon cylinder with stirring to precipitate the final polymer. The solid is washed further with diethyl ether and dried in the vacuum oven overnight at 40 0C to give the product.

Reference： [1]Current Patent Assignee: POLYMERIX - WO2008/34019, 2008, A2 Location in patent: Page/Page column 33

42
[ 21062-20-4 ]
[ 88-74-4 ]
[ 481666-54-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran	1 EXAMPLES Example 1. Preparation of a tetraaza-crown ether. 2-Nitroaniline is acylated with diglycolyl chloride in anhydrous THF, using 0.5 equivalents of diglycolyl chloride in dilute solution. A 0.1 M THF solution of diglycolyl chloride is slowly added to a 0.1 M THF solution of 2-nitroaniline, containing two equivalents of triethylamine. After TLC indicates consumption of all starting 2-nitroaniline, volatiles are removed in vacuo and the residue is partitioned between water and ethyl acetate. The ethyl acetate layer is concentrated to give Compound 1.

Reference： [1]Current Patent Assignee: THERMO FISHER SCIENTIFIC INC - WO2005/16874, 2005, A2 Location in patent: Page/Page column 53

43
[ 690994-04-8 ]
[ 21062-20-4 ]
C₂₅H₂₃NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 2h;	117 To a solution of 130 (0.05M) in dry THF with 2 eq DIEA is slowly added a 0. 1 M solution of diglycolyl chloride in dry THF with rapid stirring. After 2h, the reaction solution is concentrated in vacuo. The residue is partitioned between 0. 1 M HCI and ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate, and concentrated to give bisamide 131.

Reference： [1]Current Patent Assignee: THERMO FISHER SCIENTIFIC INC - WO2005/16874, 2005, A2 Location in patent: Page/Page column 115

44
[ 483989-10-2 ]
[ 21062-20-4 ]
[ 483989-20-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane; water	44 Bis[N-[2-(3,4,5-trimethoxyphenyl)-5-pyridyl]-2-aminoethyl]ether dimethanesulfonate EXAMPLE 44 Bis[N-[2-(3,4,5-trimethoxyphenyl)-5-pyridyl]-2-aminoethyl]ether dimethanesulfonate To an ice-cold solution of 5-amino-2-(3,4,5-trimethoxyphenyl)pyridine (203.6 mg, 0.783 mmol) synthesised as described in Reference Example 11 in methylene chloride (4 mL) were added N,N-diisopropylethylamine (0.20 mL, 1.1 mmol) and diglycolyl chloride (75.8 mg, 0.443 mmol). After being stirred in ice for 30 minutes, water was added to the reaction mixture. The mixture was extracted with methanol-chloroform (1:20), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to yield bis[N-[2-(3,4,5-trimethoxyphenyl)-5-pyridyl]carbamoylmethyl]ether as a colorless oil (224.3 mg, yield: 93%).

Reference： [1]Current Patent Assignee: KOWA COMPANY, LTD. - US2003/22886, 2003, A1

45
[ 21062-20-4 ]
[ 75-31-0 ]
[ 90716-92-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine In dichloromethane at 20℃; for 2h;

Reference： [1]Location in patent: scheme or table Kitsunai, Makoto; Miyajima, Kentaro; Mikami, Yuzuru; Kim, Shokaku; Hirasawa, Akira; Chiba, Kazuhiro [Bioscience, Biotechnology and Biochemistry, 2008, vol. 72, # 12, p. 3314 - 3317]

46
6-(3-(aminomethyl)phenyl)-N-cyclopropylquinazoline-4-amine dihydrochloride [ No CAS ]
[ 21062-20-4 ]
[ 950569-99-0 ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: 6-(3-(aminomethyl)phenyl)-N-cyclopropylquinazoline-4-amine dihydrochloride; diglycolyl chloride With triethylamine In chloroform at 20℃; for 18.5h; Heating / reflux; Stage #2: With sodium hydride In N,N-dimethyl-formamide at 0℃; for 5h; Heating / reflux;	212 4-(3-(4-(cyclopropylamino)quinazolin-6-yl)benzyl)morpholine-3,5-dione Example 212 4-(3-(4-(cyclopropylamino)quinazolin-6-yl)benzyl)morpholine-3,5-dione Triethylamine (0.363 mL, 4.59 mmol, 5 equiv.) was added to a suspension of (6-(3-(aminomethyl)phenyl)-N-cyclopropylquinazoline-4-amine dihydrochloride (Example 297) (0.300 g, 0.92 mmol, 1 equiv.) in chloroform (20 mL), followed by diglycolic acid dichloride (0.544 g, 4.59 mmol, 5 equiv.) and the mixture was then heated to reflux for 30 minutes, cooled to RT and subsequently stirred for 18 hours. The reaction mixture was evaporated to low bulk in a vacuum and the residue dissolved in DMF (5 mL). This solution was slowly added in drops at 0° C. to a suspension of sodium hydride (0.109 g, 4.59 mmol, 5 equiv.) in DMF (10 mL) and the mixture heated to reflux for 5 hours. The reaction mixture was diluted with EE (80 mL) and extracted with sat. aq. sodium hydrogencarbonate sol. (2*20 mL) and brine (20 mL), dried (MgSO4) and the solvent removed in a vacuum. After purification by column chromatography (EE/MeOH; 20:1) the desired product was obtained (212) (0.090 g, 25%).

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - US2009/69320, 2009, A1 Location in patent: Page/Page column 64

47
[ 21062-20-4 ]
[ 243989-52-8 ]
methyl 2,2'-(oxybis((1-oxo-2,1-ethanediyl)imino))bis(5-phenylbenzene-1-carboxylate) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: diglycolyl chloride; 4-amino-biphenyl-3-carboxylic acid methyl ester In ISOPROPYLAMIDE at 20℃; Stage #2: With water; sodium hydrogencarbonate In ISOPROPYLAMIDE	59.i (i) Methyl 2,2'-(oxybis((1-oxo-2,1-ethanediyl)imino))bis(5-phenylbenzene-1-carboxylate) 1.50 g (6.6 mmol) of methyl 4-aminobiphenyl-3-carboxylate, and 0.36 ml (3.0 mmol) of diglycolyl chloride were stirred in 22 ml of DMA at room temperature overnight. After completion of the reaction, an aqueous sodium hydrogen carbonate solution was added, and the precipitated solid was filtered off. The obtained residue was washed with IPE to give 1.59 g of methyl 2,2'-(oxybis((1-oxo-2,1-ethanediyl)imino))bis(5-phenylbenzene-1-carboxylate) (yield: 96%).1H-NMR (CDCl3) δ: 3.80 (6H, s), 4.40 (4H, s), 7.33-7.63 (10H, m), 7.82 (2H, dd, J=8.8, 2.2 Hz), 8.29 (2H, d, J=2.2 Hz), 8.85 (2H, d, J=8.8 Hz), 11.9 (2H, s).

Reference： [1]Current Patent Assignee: RENA SCIENCE - US2009/124620, 2009, A1 Location in patent: Page/Page column 58

48
[ 944578-53-4 ]
[ 21062-20-4 ]
[ 1103928-86-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: tert-butyl 2-amino-5-methyl-4-phenylthiophene-3-carboxylate; diglycolyl chloride In ISOPROPYLAMIDE at 20℃; for 12h; Stage #2: With water; sodium hydrogencarbonate In N,N-dimethyl-formamide	7.ii (ii) 2,2'-(Oxybis((1-oxo-2,1-ethanediyl)imino))bis(tert-butyl 5-methyl-4-phenylthiophene-3-carboxylate)A mixture of 295 mg (1.73 mmol) of diglycolyl chloride and 1.0 g (3.46 mmol) of tert-butyl 2-amino-5-methyl-4-phenylthiophene-3-carboxylate was stirred in 10 ml of DMA at room temperature for 12 hours. The reaction mixture was poured into ice water, and sodium hydrogen carbonate was then added to alkalize. The precipitate was filtered off. The filtrate was dried, and separated and purified by silica gel column chromatography to give 0.94 g of 2,2'-(oxybis((1-oxo-2,1-ethanediyl)imino))bis(tert-butyl 5-methyl-4-phenylthiophene-3-carboxylate) (yield 80%).1H-NMR (CDCl3) δ: 1.04 (18H, s), 2.12 (6H, s), 4.43 (4H, s), 7.06-7.40 (10H, m), 12.1 (2H, s).
80%	In N,N-dimethyl acetamide at 0 - 20℃;

Reference： [1]Current Patent Assignee: RENA SCIENCE - US2009/124620, 2009, A1 Location in patent: Page/Page column 39
[2]Location in patent: experimental part Yamaoka, Nagahisa; Kawano, Yasuhiko; Izuhara, Yuko; Miyata, Toshio; Meguro, Kanji [Chemical and Pharmaceutical Bulletin, 2010, vol. 58, # 5, p. 615 - 619]

49
[ 21062-20-4 ]
[ 124-40-3 ]
[ 34866-70-1 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane at 5℃;
	With triethylamine In tetrahydrofuran	1. Synthesis of tetraalkyl diglycolamide General procedure: N,N,N,N-tetraalkyl diglycolamide (Fig. S1) was synthesized by reacting diglycolyl chloride with respective dialkyl amine as per the following reaction. The reaction was carried out in THF in the presence of triethylamine. The products were washed with distilled water and dilute HCl to remove un-reacted diglycolyl chloride and dialkyl amine, respectively. Final product was purified by column chromatography. The materials were characterized by 1H-NMR (Fig. S2) and FT-IR (Fig. S3).

Reference： [1]Location in patent: experimental part Tian, Guoxin; Rao, Linfeng; Teat, Simon J.; Liu, Guokui [Chemistry - A European Journal, 2009, vol. 15, # 16, p. 4172 - 4181]
[2]Ansari, Seraj A.; Dumpala, Rama Mohana R.; Mohapatra, Prasanta K.; Verboom, Willem [Polyhedron, 2022, vol. 220]

50
[ 143-16-8 ]
[ 21062-20-4 ]
[ 342794-44-9 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃; Inert atmosphere;
	With triethylamine In tetrahydrofuran	1. Synthesis of tetraalkyl diglycolamide General procedure: N,N,N,N-tetraalkyl diglycolamide (Fig. S1) was synthesized by reacting diglycolyl chloride with respective dialkyl amine as per the following reaction. The reaction was carried out in THF in the presence of triethylamine. The products were washed with distilled water and dilute HCl to remove un-reacted diglycolyl chloride and dialkyl amine, respectively. Final product was purified by column chromatography. The materials were characterized by 1H-NMR (Fig. S2) and FT-IR (Fig. S3).

Reference： [1]Location in patent: experimental part Liu, Jiang-Fan; Yang, Hai-Jian; Wang, Wei; Li, Zhongxiao [Journal of Chemical and Engineering Data, 2008, vol. 53, # 9, p. 2189 - 2192]
[2]Ansari, Seraj A.; Dumpala, Rama Mohana R.; Mohapatra, Prasanta K.; Verboom, Willem [Polyhedron, 2022, vol. 220]

51
[ 21062-20-4 ]
[ 101711-55-1 ]
[ 1239890-83-5 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine In dichloromethane at 0℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Ng, Pei-Sze; Laing, Brian M.; Balasundarum, Ganesan; Pingle, Maneesh; Friedman, Alan; Bergstrom, Donald E. [Bioconjugate Chemistry, 2010, vol. 21, # 8, p. 1545 - 1553]

52
[ 21062-20-4 ]
[ 3380-34-5 ]
[ 1146530-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In chloroform; at 0℃; for 2.5h;Inert atmosphere;	Dimer (Batch-01)To a solution of <strong>[3380-34-5]triclosan</strong> (23 grams, 79.43 mmol) and pyridine (10.9 mL, 134.91 mmol) in chloroform (110 mL) at 0 C. under N2 atmosphere, was added a solution of diglycolyl chloride (11 grams, 64.33 mmol) in chloroform (15 mL) dropwise over a period of 30 minutes and stirred at the same temperature for 2 hours. It was then placed in a refrigerator over night. The reaction mixture was washed with water (2×100 mL), 5% Sodium bicarbonate (3×100 mL), 5% copper sulphate solution (3×100 mL) and water (2×100 mL). It was dried over sodium sulphate and the chloroform was distilled off under vacuum to get the dimer 20 (15 grams), as a yellow thick syrup. IH NMR (CDCl3) delta 4.44 (s, 2H, CH2), 6.80 (d, 1H, Ar), 6.89 (d, 2H, Ar), 7.20 (m, 3H, Ar), 7.43 (d, 1H, Ar).

Reference： [1]Patent: US8053591,2011,B2 .Location in patent: Page/Page column 62

53
[ 6096-81-7 ]
[ 21062-20-4 ]
[ 79709-71-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In tetrahydrofuran at 0 - 20℃;

Reference： [1]Location in patent: experimental part Iqbal, Mudassir; Huskens, Jurriaan; Sypula, Michal; Modolo, Giuseppe; Verboom, Willem [New Journal of Chemistry, 2011, vol. 35, # 11, p. 2591 - 2600]

54
[ 919-30-2 ]
[ 21062-20-4 ]
[ 1612772-94-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine In toluene at 0 - 20℃;
85%	With triethylamine In toluene at 0 - 20℃;
	With triethylamine In toluene at 120℃; for 24h; Inert atmosphere;

Reference： [1]Florek, Justyna; Mushtaq, Ambreen; Larivière, Dominic; Cantin, Gabrielle; Fontaine, Frédéric-Georges; Kleitz, Freddy [RSC Advances, 2015, vol. 5, # 126, p. 103782 - 103789]
[2]Hu, Yimu; Giret, Simon; Meinusch, Rafael; Han, Jongho; Fontaine, Frédéric-Georges; Kleitz, Fredd; Larivière, Dominic [Journal of Materials Chemistry A, 2019, vol. 7, # 1, p. 289 - 302]
[3]Florek, Justyna; Chalifour, Francois; Bilodeau, Francois; Lariviere, Dominic; Kleitz, Freddy [Advanced Functional Materials, 2014, vol. 24, # 18, p. 2668 - 2676]

55
[ 21062-20-4 ]
1-(2-methoxyphenyl)-10-(2,4-dimethoxyphenyl)-4,7-dioxa-1,10-diazadecane [ No CAS ]
7-(2-methoxyphenyl)-13-(2,4-dimethoxyphenyl)-1,4,10-trioxa-7,13-diazacyclopentadecane-8,12-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With pyridine In toluene at 100℃; for 72h; Inert atmosphere;
35%	With pyridine In toluene at 100℃; for 72h;	d (D) synthesis of 7- (2-methoxyphenyl) -13- (2,4-dimethoxyphenyl) -1,4,7-trioxa-7,13-diazacyclopentadecane-8,12-dione (compound 5) A flask containing anhydrous toluene (1 L) was charged with a solution of compound 4 (4.67 g, 12.0 mmol) in a mixture of anhydrous pyridine (20 mL) and anhydrous toluene (80 mL) and a solution of diglycolyl chloride (2.08 g, 12.0 mmol) was simultaneously added dropwise at 100 ° C. over 24 hours. The solution was further stirred at 100 ° C. for 2 days after which all volatiles were removed under reduced pressure. After adding water and CH 2 Cl 2, the organic layer was separated and the aqueous layer was extracted 3 times with CH 2 Cl 2. The combined organic layers were washed twice with water, dried over sodium sulfate and concentrated under reduced pressure. The crude mixture was subjected to silica gel column chromatography (PSQ 100 B, chloroform / methanol 19: 1, Rf = 0.34) and then subjected to GPC, 2.04 g (4.18 mmol, yield 35%) of Compound 5 as a colorless solid was obtained.

Reference： [1]Taki, Masayasu; Ogasawara, Hiroaki; Osaki, Hiroshi; Fukazawa, Aiko; Sato, Yoshikatsu; Ogasawara, Kimi; Higashiyama, Tetsuya; Yamaguchi, Shigehiro [Chemical Communications, 2015, vol. 51, # 59, p. 11880 - 11883]
[2]Current Patent Assignee: TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM - JP2017/52863, 2017, A Location in patent: Paragraph 0062

56
[ 21062-20-4 ]
[ 101487-61-0 ]
C₃₂H₃₈O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: tert-butyl 4-hydroxy-3-methoxy cinnamate With sodium hydride In N,N-dimethyl-formamide for 0.5h; Stage #2: diglycolyl chloride In N,N-dimethyl-formamide
72%	Stage #1: tert-butyl 4-hydroxy-3-methoxy cinnamate With sodium hydride In N,N-dimethyl-formamide for 0.5h; Stage #2: diglycolyl chloride In N,N-dimethyl-formamide	1 t-Butyl FA-Containing Diester Intermediate (3) Synthesis. t-Butyl FA (2) (2 eq) was dissolved in anhydrous dimethylformamide (DMF) to which sodium hydride (NaH, 2.2 eq) was added slowly. After 30 minutes, acyl chloride (1 eq) dissolved in 10 mL DMF was added drop-wise at 20 mL/hr. Reaction progress was monitored by thin layer chromatography (5:1 hexane:ethyl acetate as eluent). Once completed, the reaction mixture was diluted with ethyl acetate (250 mL) and washed with deionized water (2×100 mL). The organic layer was collected, dried over MgSO4, and the solvents removed in vacuo. This was purified on silica gel via flash chromatography using 5:1 hexane:ethyl acetate as eluent. (0141) t-Butyl FA-Containing (Diglycolic) Diester Intermediate (3b). (0142) Diglycolyl chloride (1 eq) was used as the acyl chloride. Yield: 72% (white powder). 1H-NMR (400 MHz, CDCl3): δ 7.56 (d, 2H, J=16.0 Hz, R-CH═CH-R), 7.10 (s, 2H, Ar-H), 7.09 (d, 2H, Ar-H), 7.08 (d, 2H, Ar-H), 6.34 (d, 2H, J=16.0 Hz, R-CH═CH-R), 4.62 (s, 4H, CH2), 3.86 (s, 6H, OCH3), 1.54 (s, 18H, 3CH3). 13C-NMR (CDCl3): δ 167.9, 166.3, 151.3, 142.8, 140.7, 134.3, 123.2, 121.4, 120.9, 111.3, 80.9, 68.1, 56.2, 28.4. Tm: 222-223° C.

Reference： [1]Ouimet, Michelle A.; Faig, Jonathan J.; Yu, Weiling; Uhrich, Kathryn E. [Biomacromolecules, 2015, vol. 16, # 9, p. 2911 - 2919]
[2]Current Patent Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY - US2016/130211, 2016, A1 Location in patent: Paragraph 0139-0142

57
[ 21062-20-4 ]
[ 950-59-4 ]
[ 74-31-7 ]
C₃₆H₄₀N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene at 90℃; for 4h; Inert atmosphere;	III-4 Example III-4 Example III-4 Under the protective atomosphere of nitrogen gas, to a 250ml four-necked flask equiped with a stirrer, a thermometer,a condensing tube and a dropping funnel, there were added 8.57g (36mmol) 2,6-di-tert-butyl-4-mercaptophenol,2.56g (15mmol) 2,2’-oxydiacetyl chloride, 10.14g (39mmol) N,N’-diphenyl-1,4-phenylene diamine and 100mL toluene,rapidly stirred, reacted at 90 degrees Celsius for 4h. Upon completion of the reaction, the solvent and water(generated during the reaction) were removed by vacuum distillation, the titled hindered phenol compound was obtainedby using column chromatography. The compound was characterized as follows : 1H NMR (300MHz, CDCl3) : δ 1.36 (18H), 4.11 (2H), 4.33 (2H), 5.32 (1H), 6.97-7.48 (16H), 7.55 (1 H); 13C NMR (75MHz, CDCl3) : δ 29.6, 34.6, 69.2, 71.9, 116.6, 119.3, 121.8, 126.2, 127.3, 127.7, 129.1, 129.5, 136.5,141.9, 142.8, 146.1, 153.5, 165.1, 189.9; C36H40N2O4S (calculated) : C 72.45, H 6.76, N 4.69, O 10.72, S 5.37; (measured) : C 72.40, H 6.71, N 4.72, O10.78, S 5.35.
	In toluene at 90℃; for 4h; Inert atmosphere;	III-4 Example III-4 Under nitrogen atmosphere, a 250ml four-necked flask equipped with a stirrer, a thermometer, a condenser and a dropping funnel was added 8.57 g (36mmol) 2,6-di-tert-butyl-4-mercaptophenol, 2.56 g (15mmol) 2,2'-oxodiacetyl chloride,10.14 g (39mmol) N,N'-diphenyl-1,4-phenylenediamine and 100mL of toluene, stirring rapidly, reaction at 90 deg. C for 4h. After completion of the reaction, the solvent was evaporated under reduced pressure and a small amount of water produced, purified by column chromatography to obtain the final product.
	In toluene at 90℃; for 4h; Inert atmosphere;	4 Embodiment 4 Under the protective atmosphere of nitrogen, adding 8.57 g (36mmol) 2,6-di-tert-butyl-4-mercapto-phenol, 2.56 g (15mmol) 2, the 2 [...] -oxide bis acetyl chloride, 10.14 g (39mmol) N, N '-diphenyl -1,4-phenylenediamine and 100 ml toluene, in the 250 ml flask which is provided with a stirrer, thermometer, condenser pipe and a dropping funnel, rapid stirring, 90 °C reaction 4h. After the end of reaction, the solvent is removed by reduced pressure distillation and generation of a small amount of water, and through the column chromatography separation to obtain the final shielding phenol product.

Reference： [1]Current Patent Assignee: CHINA PETROCHEMICAL CORPORATION - EP2952505, 2015, A1 Location in patent: Paragraph 0550; 0551; 0552
[2]Current Patent Assignee: CHINA PETROCHEMICAL CORPORATION - CN105315183, 2016, A Location in patent: Paragraph 0879; 0880; 0881; 0882; 0883; 0884; 0885
[3]Current Patent Assignee: CHINA PETROCHEMICAL CORPORATION - CN105272892, 2016, A Location in patent: Paragraph 0307; 0308; 0309; 0310; 0311; 0312; 0313

58
[ 21062-20-4 ]
[ 111-40-0 ]
1-oxa-4,7,10-triazacyclopentadecane-3,11-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.5 g	With triethylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	Synthesis of 1-oxa-4,7,10-triazacyclododecane-3,11-dione (OTDD) General procedure: Thionyl chloride (6.52 mL, 90 mmol) was added slowly toa solution of 2, 20-oxydiacetic acid (2.01 g, 15 mmol) inethyl acetate (30 mL) at 0-5 C under nitrogen atmosphere. The reaction mixture was stirred for 30 min at0-5 C and at room temperature for the same durationfollowed by refluxing along with stirring at 70 C over aperiod of 7 h. The highly hygroscopic and reactive compound(2, 20-oxydiacetyl chloride) yielded by concentratingthe solution under reduced pressure (Scheme 1). Both 2, 20-oxydiacetyl chloride (2 g, 11.6 mmol) and 1,5-diamino-3-aza-pentane (1.29 mL, 12 mmol) were diluted by addingdry THF (120 mL) separately and added drop wisesimultaneously by dropping funnels to ice cooled dry THF(350 mL) under nitrogen-atmosphere. During drop wiseaddition of these reactants, triethylamine (5.02 mL,36 mmol) was added to catalyze the reaction. The reactionmixture was stirred at 0-5 C followed by overnight stirringat room temperature. Progress of reaction was monitoredby TLC. Solvent was removed under reducedpressure to yield the macrocyclic product OTDD, whichwas purified by washing with chloroform (5 mL) 8-10times followed by etheration and vacuum drying to yieldthe pure compound (Fig. 1).

Reference： [1]Yadav, Neelam; Chuttani, Krishna; Mishra, Anil K.; Singh, Bachcha [Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015, vol. 83, # 3-4, p. 299 - 307]

59
[ 1120-48-5 ]
[ 21062-20-4 ]
[ 342794-43-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium hydroxide; In diethyl ether; water; at 20℃; for 2.5h;	General procedure: Diglycolyl chloride (0.85 g, 5 mmol) in Et2O (30 mL) was added dropwise to a solution of amine (30 mmol) and NaOH (1.2 g, 30mmol) in water (36 mL) at 0 C over 30 min. The mixture was stirred at 0 C for 2 h, and then the phases were separated. The aqueous layer was saturated with NaCl and extracted with Et2O (3 × 30 mL). An aqueous solution of 10 % HCl (20 mL) was added to the combined organic layers. The mixture was shaken vigorously to facilitate formation of clumps of ammonium salts, floating between the two phases. The organic layer was washed two more times with HCl solution (20 mL) and then filtered through a glass frit (G3). A poly(4-styrenesulfonic acid) solution (4 wt%, 25 mL) in water was added to the organic layer. The mixture was shaken vigorously to facilitate formation of polymeric salts as an amorphous material floating between the layers. The organic layer was washed with water and then separated from the polymeric salt. It was dried with MgSO4, where upon the solvent was removed by vacuum evaporation to afford the DGAs, which had a purity of ?97 % according to the 1H NMR spectra.

Reference： [1]Synlett,2016,vol. 27,p. 2463 - 2466

60
[ 626-23-3 ]
[ 21062-20-4 ]
C₂₀H₄₀N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydroxide In diethyl ether; water at 0 - 5℃; for 2.5h;	General Procedure 1: Synthesis of Diglycolamides by Schotten-Baumann Reaction General procedure: Diglycolyl chloride (0.85 g, 5 mmol) in Et2O (30 mL) was added dropwise to a solution of amine (30 mmol) and NaOH (1.2 g, 30mmol) in water (36 mL) at 0 °C over 30 min. The mixture was stirred at 0 °C for 2 h, and then the phases were separated. The aqueous layer was saturated with NaCl and extracted with Et2O (3 × 30 mL). An aqueous solution of 10 % HCl (20 mL) was added to the combined organic layers. The mixture was shaken vigorously to facilitate formation of clumps of ammonium salts, floating between the two phases. The organic layer was washed two more times with HCl solution (20 mL) and then filtered through a glass frit (G3). A poly(4-styrenesulfonic acid) solution (4 wt%, 25 mL) in water was added to the organic layer. The mixture was shaken vigorously to facilitate formation of polymeric salts as an amorphous material floating between the layers. The organic layer was washed with water and then separated from the polymeric salt. It was dried with MgSO4, where upon the solvent was removed by vacuum evaporation to afford the DGAs, which had a purity of ≥97 % according to the 1H NMR spectra.

Reference： [1]Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem [Synlett, 2016, vol. 27, # 17, p. 2463 - 2466]

61
[ 106-20-7 ]
[ 21062-20-4 ]
2,2’-oxybis(N-(2-ethylhexyl)acetamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydroxide In diethyl ether; water at 20℃; for 15h;	General Procedure 1: Synthesis of Diglycolamides by Schotten-Baumann Reaction General procedure: Diglycolyl chloride (0.85 g, 5 mmol) in Et2O (30 mL) was added dropwise to a solution of amine (30 mmol) and NaOH (1.2 g, 30mmol) in water (36 mL) at 0 °C over 30 min. The mixture was stirred at 0 °C for 2 h, and then the phases were separated. The aqueous layer was saturated with NaCl and extracted with Et2O (3 × 30 mL). An aqueous solution of 10 % HCl (20 mL) was added to the combined organic layers. The mixture was shaken vigorously to facilitate formation of clumps of ammonium salts, floating between the two phases. The organic layer was washed two more times with HCl solution (20 mL) and then filtered through a glass frit (G3). A poly(4-styrenesulfonic acid) solution (4 wt%, 25 mL) in water was added to the organic layer. The mixture was shaken vigorously to facilitate formation of polymeric salts as an amorphous material floating between the layers. The organic layer was washed with water and then separated from the polymeric salt. It was dried with MgSO4, where upon the solvent was removed by vacuum evaporation to afford the DGAs, which had a purity of ≥97 % according to the 1H NMR spectra.

Reference： [1]Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem [Synlett, 2016, vol. 27, # 17, p. 2463 - 2466]

62
[ 21062-20-4 ]
1-(3,3-dimethylbutyrylamino)-8-amino-3,6-dichlorocarbazole [ No CAS ]
2,2’-oxydiacetylbis(1-amino-8-(3,3-dimethylbutyrylamino)-3,6-dichlorocarbazole) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In tetrahydrofuran at 20℃;

Reference： [1]Bąk, Krzysztof M.; Masłowska, Krystyna; Chmielewski, Michał J. [Organic and Biomolecular Chemistry, 2017, vol. 15, # 28, p. 5968 - 5975]

63
[ 21062-20-4 ]
[ 10185-68-9 ]
2,2'-oxybis{N-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]acetamide} [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With 4-methyl-morpholine In dichloromethane at 0 - 20℃; for 12h;

Reference： [1]Maciejewska; Zabiński; Rezler; Kaźmierczak; Collins; Ficker; Cushion [MedChemComm, 2017, vol. 8, # 10, p. 2003 - 2011]

64
[ 21062-20-4 ]
C₄₅H₆₅N₉O₉ [ No CAS ]
C₉₄H₁₃₂N₁₈O₂₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.5h; Inert atmosphere;	a) Muitimerization of amine-containing monomeric macrocydes using bis- or tris-acyl chloride- activated linkers: The corresponding acyl chloride (0.35 mmol, 1.0 eq.), freshly prepared and under Argon atmosphere, was dissolved in anhydrous CH2Cl2(5 mL; note that iarger scale reactions required more-concentrated solution to produce higher-yielding dimerizations). Monomeric macrocycle (2, 3 or 4 eq. for bis-, tris-, or tefra-acyl chlorides), optimally supplied as the free-base / non-salted form of the reacting amine center, was added to the flask, followed by dropwise addition of DIPEA (3.5 mmol, 10.0 eq); NB - this order of addition proved to be very important. The reaction was monitored by LC-MS. After 30 min., the reaction was complete, and longer stirring times did not affect the product ratio. The solvents were removed in vacuo and the crude material was submitted to reverse-phase chromatography (Biotage) to obtain the purified product.

Reference： [1]Current Patent Assignee: ZEALAND PHARMA A/S - WO2018/85921, 2018, A1 Location in patent: Page/Page column 31; 32

65
[ 1120-48-5 ]
[ 21062-20-4 ]
[ 342794-43-8 ]
[ 135447-09-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 250 g 2: 200 g	Stage #1: n-dioctylamine; diglycolyl chloride With triethylamine In dichloromethane at 20℃; for 5h; Stage #2: With water	1-3 2) Adding 200 mL of dichloromethane to diglycoyl chloride.After dissolving 202 g of triethylamine and 482 g of di-n-octylamine in 200 mL of dichloromethane, it was slowly added to a diglycolyl chloride solution, and reacted at room temperature for 5 hours. After the reaction is over, dilute hydrochloric acid is added.After stirring for 1 hour, it was filtered. The filtrate was concentrated to give the crude TODGA product.The crude product was purified by column chromatography to yield purified TODGA 250 g.(3) The filter cake was washed with water to remove triethylamine hydrochloride. The filter cake was recrystallized from a petroleum ether/ethyl acetate mixed solvent having a volume ratio of 3/1 to obtain 200 g of monooxalyl carboxylic acid.The monooxalyl carboxylic acid according to the existing method (Solvent Extr. IonExch., 2007, 25, 205) The reaction was continued to obtain 105 g of TODGA, and the total yield of TODGA was 61%.

Reference： [1]Current Patent Assignee: ZHONGHONG PULIN BEIJING MEDICAL PRODUCTS HIGH NEW - CN109824532, 2019, A Location in patent: Paragraph 0026; 0028-0030; 0032-0034; 0036; 0037

66
[ 21062-20-4 ]
[ 90990-95-7 ]
2,2'-oxybis(N-(4-(4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazine-1-carbonyl)phenyl)acetamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate In N,N-dimethyl-formamide Inert atmosphere;	4.1.22 Compounds 7aa-7fc were prepared as the following procedure General procedure: The corresponding reduced benzamides 6a-6f were mixed with different dichloride linkers. They were dissolved in anhydrous DMF in a 2 to 1 ratio under argon protection. The dichloride linkers where diluted in anhydrous DMF and added slowly. It was stirred overnight and monitored by TLC after 24h. The reaction was stopped by reducing down the solvent and purified with PTLC in DCM/EtOH.