Name: 955094-26-5|2,5-Dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate|95%
Brand: Ambeed
SKU: A100037
Rating: 96 (25 reviews)

1
[ 1174157-65-3 ]
[ 1610762-73-6 ]
[ 955094-26-5 ]
[ 1610762-75-8 ]

Yield	Reaction Conditions	Operation in experiment
35%	With triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Liu, Fang; Mu, Jing; Wu, Xiangyang; Bhattacharjya, Surajit; Yeow, Edwin Kok Lee; Xing, Bengang [Chemical Communications, 2014, vol. 50, # 47, p. 6200 - 6203]

2
[ 955094-26-5 ]
O-[N-(3-maleimidopropionyl)aminoethyl]-O’-[3-(N-(2-aminoethyl)amino)-3-oxopropyl]ethylene glycol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 20 °C / Cooling with ice 2: trifluoroacetic acid / dichloromethane / 2 h / 0 - 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 20 °C / Cooling with ice 2: trifluoroacetic acid / dichloromethane / 2 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2015/104407, 2015, A1
[2]Current Patent Assignee: ASANA BIOSCIENCES LLC; MERSANA THERAPEUTICS, INC. - WO2015/54669, 2015, A1

3
[ 955094-26-5 ]
N-(tert-butyloxycarbonyl)-1,2-ethanediamine hydrochloride [ No CAS ]
tert-butyl (16-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4,14-dioxo-7,10-dioxa-3,13-diazahexadecyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine In acetonitrile at 20℃; Cooling with ice;	1 To an ice-cold suspension of maleimido-EG2-NHS ester (O-[N-(3-maleimidopropionyl)aminoethyl]-O'-[3-(N-succinimidyloxy)-3-oxopropyl]ethylene glycol, 1.2 g, 2.82 mmol) and Boc-diaminoethane hydrochloride (560 mg, 2.82 mmol) in ACN (15 mL) was added TEA (0.571 g, 5.64 mmol) drop-wise while stirring. The resulting mixture was brought to room temperature and the stirring continued overnight at room temperature. Additional BOC-diaminoethane hydrochloride was added (110 mg) to drive the reaction to completion. The reaction mixture was concentrated under vacuum and the residue purified on RP-HPLC (0-100% ACN in water) to give Boc-diaminoethane-EG2-maleimide as a colorless solid (1.18 g, 89% yield). ESI MS: calculated C21H35N4O8 [M+H+] 471.3. found 471.2.
89%	With triethylamine In acetonitrile at 20℃; Cooling with ice;	1 To an ice-cold suspension of maleimido-EG2-NHS ester (O-[N-(3-maleimidopropionyl)aminoethyl]-O'-[3-(N-succinimidyloxy)-3-oxopropyl]ethylene glycol, 1.2 g, 2.82 mmol) and Boc-diaminoethane hydrochloride (560 mg, 2.82 mmol) in ACN (15 mL) was added TEA (0.571 g, 5.64 mmol) drop-wise while stirring. The resulting mixture was brought to room temperature and the stirring continued overnight at room temperature. Additional BOC-diaminoethane hydrochloride was added (110 mg) to drive the reaction to completion. The reaction mixture was concentrated under vacuum and the residue purified on RP-HPLC (0-100% ACN in water) to give Boc-diaminoethane-EG2-maleimide as a colorless solid (1.18 g, 89% yield). ESI MS: calculated C21H35N4O8 [M+H+] 471.3. found 471.2.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2015/104407, 2015, A1 Location in patent: Paragraph 0860; 0861
[2]Current Patent Assignee: ASANA BIOSCIENCES LLC; MERSANA THERAPEUTICS, INC. - WO2015/54669, 2015, A1 Location in patent: Paragraph 00467

4
[ 955094-26-5 ]
tert-butyl (2-aminoethyl)carbamate hydrochloride [ No CAS ]
tert-butyl (16-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4,14-dioxo-7,10-dioxa-3,13-diazahexadecyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine In acetonitrile at 20℃; Cooling with ice;	1 Synthesis of EG2-maleimide: (O-[N-(3-maleimidopropionyl)aminoethyl]-O'-[3-(N-(2-aminoethyl)amino)-3-oxopropyl]ethylene glycol) Example 1 Synthesis of EG2-maleimide: (O-[N-(3-maleimidopropionyl)aminoethyl]-O'-[3-(N-(2-aminoethyl)amino)-3-oxopropyl]ethylene glycol) To an ice-cold suspension of maleimido-EG2-NHS ester (O-[N-(3-maleimidopropionyl)aminoethyl]-O'-[3-(N-succinimidyloxy)-3-oxopropyl]ethylene glycol, 1.2 g, 2.82 mmol) and Boc-diaminoethane hydrochloride (560 mg, 2.82 mmol) in ACN (15 mL) was added TEA (0.571 g, 5.64 mmol) dropwise while stirring. The resulting mixture was brought to room temperature and the stirring continued overnight at room temperature. Additional BOC-diaminoethane hydrochloride was added (110 mg) to drive the reaction to completion. The reaction mixture was concentrated under vacuum and the residue purified on reverse phase HPLC (0-100% ACN in water) to give Boc-diaminoethane-EG2-maleimide as a colorless solid (1.18 g, 89% yield). ESI MS: calculated C21H35N4O8 [M+H]+ 471.3. found 471.2.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2015/366982, 2015, A1 Location in patent: Paragraph 0898; 0899

5
[ 955094-26-5 ]
thiopropionic acid-Asn-Leu-His-Lys-Cys-Gln-Leu-Arg-Cys-Ser-Ser-Leu-Gly-Leu-Leu-Gly-Arg-Cys-Ala-Gly-Ser-Bip-Cys-Ala-Cys-Val-CONH₂ [ No CAS ]
C₁₃₆H₂₁₈N₄₀O₃₈S₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In aq. phosphate buffer	IV Example IV Chemical Synthesis of Maleimide Activated mini-CD4 via a PEO₂Linker (miniCD4-PEO₂-mal) (see FIG. 3) Example IV Chemical Synthesis of Maleimide Activated mini-CD4 via a PEO2 Linker (miniCD4-PEO2-mal) (see FIG. 3) (0264) mCD4-PEO2-maleimide differs from the compound mCD4-SMPH in terms of the type of linker. For reasons of solubility, a polyethylene oxide (PEO2) linker which is more hydrophilic was incorporated between miniCD4 and the maleimide group. Synthesis: (0265) A solution of 10 mg of mCD4 (MW: 2897; 3.4 mmoles) in 1 ml of H2O was diluted in 1 ml of phosphate buffer 0.1 M pH 8. 4.5 mg of NHS-PEO2-Maleimide (MW: 325; 13.8 mmoles; 4 equiv) were added to this cloudy solution in 20 μl of DMSO with stirring. After 10 minutes, 85% (HPLC) of the starting materials was converted into maleimide derivative. Because of the low stability of the maleimide group at pH 8, the coupling reaction was directly loaded onto a SepaK C18 column calibrated with 10% CH3CN in aqueous TFA 0.08%. The maleimide derivative was eluted with 50% CH3CN. After freeze drying, the compound was then purified on a semi preparative column. Yield: 5.2 mg (48%), final purity: 77%. (0266) ES+: 3205.3938 (expected monoisotopic M: 3205.4211), QTOF Micro Waters MaxEnt1. (0267) HPLC conditions: (0268) Analytic: Nucleosil 5 C18 300 (4.6×150 mm); linear gradient 25 to 45% CH3CN in 0.08% aqueous TFA in 20 minutes at a flow rate of 1 ml/min. Detection: 230 nm. mCD4 Rt=10.7 minutes; mCD4-PEO2-Mal Rt=12.8 minutes. (0269) Semi preparative: Nucleosil 5 C18 300 (10×250 mm); linear gradient 25 to 45% CH3CN in 0.08% aqueous TFA for 20 minutes at a flow rate of 6 ml/min. (0270) Detection: 230 nm. mCD4-PEO2-Mal Rt=11.4.

Reference： [1]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; INSTITUT PASTEUR; COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES; UNIVERSITY OF PARIS SUD - US9295730, 2016, B2 Location in patent: Page/Page column 38

6
[ 1069-79-0 ]
[ 955094-26-5 ]
C₅₅H₁₀₀N₃O₁₄P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trimethylamine In N,N-dimethyl-formamide at 20℃; for 2h;

Reference： [1]Hu, Junjie; Liu, Fei; Ju, Huangxian [Angewandte Chemie - International Edition, 2016, vol. 55, # 23, p. 6667 - 6670][Angew. Chem., 2016, vol. 128, # 23, p. 6779 - 6782,4]

7
[ 955094-26-5 ]
Tpa-NLHK₅CQLRCSSLGLLGRCAGS-Bip-CACV-amide [ No CAS ]
mCD_4.1Mal [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In aq. phosphate buffer; dimethyl sulfoxide for 0.166667h;	General protocol for activated miniCD4 peptides synthesis (Lys5/1 1 (Νε- maleimide) miniCD4 peptides) General procedure: General protocol for activated miniCD4 peptides synthesis (Lys5/1 1 (Νε- maleimide) miniCD4 peptides) To 51 mg of miniCD4 peptide in 26 ml of water was slowly added 3 ml of 0.1 M sodium phosphate buffer pH7.2 under mild agitation to avoid foaming. NHS-PEG2- Maleimide (75 mgs, 10 molar equivalents) in 750 μ of DMSO was dropwise added to the peptide solution. After 10 minutes, the reaction mixture was acidified by 1.2 ml of pure AcOH and purified by C18 RP-MPLC using the same conditions as for miniCD4 peptide. Activated miniCD4 peptides were controlled by MS using positive mode.

Reference： [1]Current Patent Assignee: UNIVERSITY OF PARIS SACLAY - WO2016/62854, 2016, A1 Location in patent: Page/Page column 27

8
[ 955094-26-5 ]
N₂'-deacetyl-N₂'-(3-mercapto-1-oxopropyl)maytansine [ No CAS ]
C₅₃H₇₁ClN₆O₁₉S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With potassium phosphate In tetrahydrofuran; water at 20℃; for 1h;	3 Synthesis of DM1-Mal-PEG2-NHS [137] A solution of N 2'-deacetyl-N 2 '- (3-mercapto-1-oxopropyl) - maytansine (DM 1, 13.4 mg, 0.0182 mmol) was prepared in 0.70 mL of THF and succinimidyl- [ (N-maleimidopropionamido) -diethyleneglycol] ester (NHS-PEG2-maleimide, Quanta Biodesign, 11.6 mg, 0.0273 mmol) was dissolved in aqueous potassium phosphate buffer (50 mM, pH 6) and THF 2: 1 / V) mixture. The reaction was allowed to proceed for 1 hour with stirring at room temperature and TLC analysis indicated the reaction was complete. The crude reaction mixture was purified by chromatography on silica, eluting with 8% ethanol in methylene chloride; the solvent was removed in vacuo to give 6.0 mg (28% yield) of the desired product

Reference： [1]Current Patent Assignee: IMMUNOGEN INC - JP2015/163622, 2015, A Location in patent: Paragraph 0091

9
[ 955094-26-5 ]
4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl(11S,11aS)-11-hydroxy-7-methoxy-8-(4-((2-((5-((5-(5-methoxy-1H-indole-1-carbonyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-imidazol-4-yl)amino)-4-oxobutoxy)-2-methylene-5-oxo-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate [ No CAS ]
(11S,11aS)-4-((2S,5S)-19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,17-trioxo-10,13-dioxa-3,6,16-triazanonadecanamido)benzyl-11-hydroxy-7-methoxy-8-(4-(2-(5-(5-(5-methoxy-1H-indole-1-carbonyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-imidazol-4-ylamino)-4-oxobutoxy)-2-methylene-5-oxo-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With benzotriazol-1-ol; triethylamine at 20℃; for 1.5h;	14.I Part I To a solution of compound 37 (-16 mg, 14 jimol) in dry (i mL) was added HOBt (3.7 mg, 27 imoi), 2,5-dioxopyrrolidin--1 -yl 3-(2-(2-(3-(2,5-dioxo-25-dihydro- 1 El-pyrrol -I yi)propanamido)ethoxy)ethoxy)propanoate (11.6 mg, 27 .imol) and triethylamine (2.1 .tL, 15l.trnol). The mixture was stirred for -i.5 h at room temperature at which point LCMS indicated that the reaction was complete. The reaction mixture was then purified by preparative HPLC (water:ACN both containing 0.1% formic acid; gradient: 10-90% over 25 mm) to give (11. 11 aS)-4-((2S,5 S)- 1 9-(2,5-dioxo-2,5--dihydro- 1H-pyrrol-1 -yl)-5-isopropyl--2--methyl-4,7, I 7- trioxo- 10,1 3-dioxa-3,6, I 6-triazanonadecanamido)benzyi 11 -hydroxy--7-methoxy-8-(4-(2--(5-(5- (5-methoxy- i[I-indoie-i -carbonyi)-1 -methyl -1 El-pyrrol -3-ylcarbamoyl)- I -methyl- IH-pyrroi-3- ylcarbamoyl)- i-methyl- IH-imidazol-4-ylamino)-4-oxobutoxy)-2-methyiene-5-oxo-2,3, 11, 11 a- tetrahydro- 1H-henzo[e]pyrroio[i ,2-aj [1,4 jdiazepine- I 0(5H)-carboxyiate (38) as a colorless solid (3.2 mg, 15% yield for two steps starting from compound 37). ESI-MS Caicd for C74T:186N15019 1488.6 (M-f-Fi); found 1487.8.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2017/201132, 2017, A2 Location in patent: Paragraph 0416; 0434; 0435

10
[ 955094-26-5 ]
N-(5-((5-(5-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)-1H-indole-1-carbonyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrole-3-yl)-4-(4-(((S)-7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrolo[1,2-a][1,4]diazepin-8-yl)oxy)butanamido)-1-methyl-1H-imidazole-2-carboxamide [ No CAS ]
N-(5-((5-(5-((2S,5S)-19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,17-trioxo-10,13-dioxa-3,6,16-triazanonadecanamido)-1H-indole-1-carbonyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-4-(4-(((S)-7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)butanamido)-1-methyl-1H-imidazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38.1%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h;	20.C Part C To a solution of compound 45 (6 mg, 6.02 limo1) inDMF (0.5 ml) was added HOBt (0298 mg, 2.209 llmol), 2,5-dioxopyrrolidin-1 -yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro- I H-pyrrolI -yl)propanamido)ethoxy)ethoxy)propanoate (0.940 mg, 2209 iimol) and triethylamine (0.308 ul, 2209 urnol). The mixture was stirred 16 hr at room temp. [C-MS showed the completion of the reaction. The solvent was removed and the crude product purified by HPLC (0.1 N formic Acid 10-90% ACN/Water) to give N-(5-( 5-(5-((2S,5 5)-i 9-(2,5-dioxo-2,5-dihydro- 1H-pyrrol- I - yl)-5-isopropyl-2-methyl-4,7. I 7-trioxo-i 0,1 3-dioxa-3,6, I 6-triazanonadecanamido)- 1 H-indole-l - carbonyl)- 1 -methyl-i H-pyrrol-3 -yl)carbamoyi)- i-methyl-i H-pyrroi-3 -yi)-4-(4-(((S)-7-methoxy- 2-methylene-5-oxo-2,3, 5,1 1 a-tetrahydro-IH-benzo[e]pyrrolo[1 ,2-a][ I ,4]diazepin-8- yi)oxy)butanamido)-i-methyl-1H-imidazole-2-carboxamide (46) (1 mg, 0.765 jimol, 38.1 % yield) ESI MS: C65H75N15015 (M+H) 13066; found 1306.6.
38.1%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h;	To a solution of compound 85 (6 mg, 6.02 µmol) in DMF (0.5 ml) was added HOBt (0.298 mg, 2.209 µmol), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (0.940 mg, 2.209 µmol) and triethylamine (0.308 µl, 2.209 µmol). The mixture was stirred 16 h at room temp. LC-MS showed the completion of the reaction. The solvent was removed and the crude product purified by RP HPLC (0.1 N formic Acid 10-90% MeCN/Water) to give 86 (1.0 mg, 0.765 µmol, 38.1 % yield). ESI MS: C65H75N15O15 (M+H) 1306.6; found 1306.6.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2017/201132, 2017, A2 Location in patent: Paragraph 0446; 0451; 0452
[2]Thomas, Joshua D.; Yurkovetskiy, Aleksandr V.; Yin, Mao; Bodyak, Natalya D.; Gumerov, Dmitry R.; Tang, Shuyi; Kelleher, Eoin; Jones, Brian D.; Protopopova, Marina; Qin, LiuLiang; Uttard, Alex; Demady, Damon R.; Lowinger, Timothy B. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 72]

11
[ 955094-26-5 ]
(S)-3-aminopropyl 4-(4-(4-(4-(7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate [ No CAS ]
(S)-1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,13-dioxo-7,10-dioxa-4,14-diazaheptadecan-17-yl 4-(4-(4-(4-(7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 2h;	21 Synthesis of (S,Z)-1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,13-dioxo-7,10-dioxa-4,14-diazaheptadecan-17-yl 4-(4-(4-(4-(7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (54) Example 21 Synthesis of (S,Z)-1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,13-dioxo-7,10-dioxa-4,14-diazaheptadecan-17-yl 4-(4-(4-(4-(7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (54) To a solution of compound 41 (10 mg, 0.014 mmol) in dry DMF (˜1 mL) was added HOBt (2.331 mg, 0.015 mmol), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (47 mg, 0.015 mmol) and triethylamine (5.79 μl, 0.042 mmol). The mixture was stirred for ˜2 h at room temperature at which point LCMS indicated that the reaction was complete. The reaction mixture was then purified by preparative HPLC (water:ACN both containing 0.1% formic acid; gradient: 10-90% over 25 min) to give the title compound (54) (11 mg, 77% yield) an off white amorphous solid. ESI MS: C52H60N10O13 1033.1; found 1033.2.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2017/369453, 2017, A1 Location in patent: Paragraph 0740; 0741

12
[ 955094-26-5 ]
(S)-3-(4-(4-(4-(4-((S)-7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)propyl 2-aminopropanoate formate [ No CAS ]
(S)-3-(4-(4-(4-(4-((S)-7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)propyl 16-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-2-methyl-4,14-dioxo-7,10-dioxa-3,13-diazahexadecan-1-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃;	15.C Part C: Part C To compound 47 (22 mg, 0.026 mmol), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (3.85 mg, 9.04 μmol), HOBt (1.384 mg, 9.04 μmol) and DMF (0.5 ml) at room temperature was added triethylamine (1.890 μl, 0.014 mmol). The reaction was monitored by LC/MS. When complete the reaction mixture was purified by reversed phase chromatography using acetonitrile/water buffered with 0.1% formic acid to give the title compound (48) (16 mg, 55% yield). ESI MS: C56H66N10O14 (M+H) 1103.1; found 1103.1.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2017/369453, 2017, A1 Location in patent: Paragraph 0723; 0728; 0729

13
[ 955094-26-5 ]
(S)-3-(4-(4-(4-(4-(7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)propyl 3-aminopropylcarbamate [ No CAS ]
(S)-3-(4-(4-(4-(4-(7-methoxy-2-methylene-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)propyl 1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,13-dioxo-7,10-dioxa-4,14-diazaheptadecan-17-ylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide for 2h;	25.D Part D: To compound 61 (20.4 mg, 0.025 mmol), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (12.65 mg, 0.030 mmol) and HOBt (4.56 mg, 0.030 mmol) in DMF (1.5 mL) was added triethylamine (10.37 μl, 0.074 mmol) and the reaction was monitored by LC/MS. After 2 h the crude product was purified by preparative HPLC using a gradient from 10-90% acetonitrile/water buffered with 0.1% formic acid to the title compound 62 as an off white amorphous solid. (16 mg, 57% yield). ESI MS: C56H68N12O14 (M+H) 1133.2.1; found 1132.7.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2017/369453, 2017, A1 Location in patent: Paragraph 0748; 0755; 0756

14
[ 955094-26-5 ]
(11S,11aS)-4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl 11-hydroxy-8-(4-(5-(4-(5-(3-hydroxypropylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)phenylcarbamoyl)-1-methyl-1H-pyrrol-3-ylamino)-4-oxobutoxy)-7-methoxy-2-methylene-5-oxo-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate [ No CAS ]
(11S,11aS)-4-((2S,5S)-19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,17-trioxo-10,13-dioxa-3,6,16-triazanonadecanamido)benzyl 11-hydroxy-8-(4-(5-(4-(5-(3-hydroxypropylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)phenylcarbamoyl)-1-methyl-1H-pyrrol-3-ylamino)-4-oxobutoxy)-7-methoxy-2-methylene-5-oxo-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 1.5h;	38.C Part C: Part C Compound 76 (14 mg, 0.013 mmol) in dry DMF (0.5 mL) was added HOBt (3.6 mg, 0.026 mmol), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (purchased from Quanta Biodesign, 11.3 mg, 0.026 mmol), and triethylamine (2.0 μL, 0.015 mmol). The mixture was stirred ˜1.5 h at room temperature. The crude product was purified by reverse phase HPLC (water:ACN both containing 0.1% formic acid; gradient: 10-90% over 25 min) to give the title compound 77 as a pale yellow solid (12.3 mg, 68% yield). ESI-MS: C69H85N12O18 (M+H) 1369.6; found 1369.6.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2017/369453, 2017, A1 Location in patent: Paragraph 0781; 0786; 0787

15
[ 955094-26-5 ]
4-(4-(4-(4-(((S)-3-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)-8-methoxy-6-oxo-12a,13-dihydro-6H-benzo[5,6][1,4]diazepino[1,2-a]indol-9-yl)oxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid [ No CAS ]
4-(4-(4-(4-(((S)-3-((2S,5S)-19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,17-trioxo-10,13-dioxa-3,6,16-triazanonadecanamido)-8-methoxy-6-oxo-12a,13-dihydro-6H-benzo[5,6][1,4]diazepino[1,2-a]indol-9-yl)oxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 2h;	47.Q Part Q: Part Q Compound 101 (6 mg, 6.8 μmol), HOBt (2 eq, 1.8 mg), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (2 eq, 5.8 mg), TEA (1.1 eq, 1 μL) and anhydrous DMF (1 ml) was stirred at room temperature. After 2 h the crude product was purified by preparative HPLC (0.1% HCOOH) to give 4-(4-(4-(4-(((S)-3-((2S,5S)-19-(2,5-dioxo-2, 5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,17-trioxo-10,13-dioxa-3,6,16-triazanonadecanamido)-8-methoxy-6-oxo-12a,13-dihydro-6H-benzo[5,6][1,4]diazepino[1,2-a]indol-9-yl)oxy)butanamido)-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid (102) (3 mg, 37% yield). ESI MS: C60H68N12O15 (M+H) 1198.2; found 1197.5.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2017/369453, 2017, A1 Location in patent: Paragraph 0837; 0838

16
[ 955094-26-5 ]
S-{2-[(3-aminopropyl){(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-L-cysteine [ No CAS ]
S-{2-[(3-Aminopropyl) {(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; acetic acid; trifluoroacetic acid	S-{2-[(3-Aminopropyl) {(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine/trifluoroacetic Acid (1:1) S-{2-[(3-Aminopropyl) {(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine/trifluoroacetic Acid (1:1) 30 mg (36 μmol) of S-{2-[(3-aminopropyl){(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-L-cysteine/trifluoroacetic acid (1:1) (Intermediate C71) together with 16.9 mg (40 μmol) of 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-[2-(2-{3-[(2,5-dioxopyrrolidin-1-yl)oxy]-3-oxopropoxy}ethoxy)ethyl]propanamide were initially charged in 1.5 ml of DMF, and 10.9 mg (108 μmol) of 4-methylmorpholine were added. The reaction mixture was stirred at RT overnight, and 7.58 mg (0.13 mmol) of acetic acid were then added. The reaction mixture was purified directly by preparative RP-HPLC (column: Reprosil 250*30; 10μ, flow rate: 50 ml/min, MeCN/water, 0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 33.4 mg (80% of theory) of the compound S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl)-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine. LC-MS (Method 1): Rt=1.34 min; MS (ESIpos): m/z=1027 (M+H)+.

Reference： [1]Current Patent Assignee: BAYER AG - US2018/169256, 2018, A1

17
[ 955094-26-5 ]
C₃₂H₅₉N₇O₁₇*C₂HF₃O₂ [ No CAS ]
C₄₆H₇₇N₉O₂₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 1h;	1.F [00650] The TFA-salt of compound 6 ( 1 19 mg, 0.128 mmol) was dissolved in DMF ( 1.7 mL), then DIEA (5 equivalents) was added. The reaction mixture was cooled to 0 °C, then 2,5- di oxopyrrolidin- 1 ~yl3 ~(2-(2-(3 -(2, 5-dioxo-2, 5-dihydro- 1 H-pyrrol- 1 yl)propanamido)ethoxy) ethoxy)propanoate (109 mg, 0.256 mmol ) in DMF (0.5 mL) was added. Stirring was continued for 30 minutes at 0 °C and then at room temperature for 30 minutes, when LC-MS analysis indicated the reaction was complete. The reaction mixture was concentrated by rotary evaporation and purified by RP CI 8 column CombiFlash chromatography using ACN/water containing HO Ac (0.1%) gradient as eluant, to give compound 7 (86 nig, 60% yield). (1622) [00651] lH NMR (400 MHz, DM SO-ri*. + 20 μ. of D2O) δ 12.07-12.25 (bs, 1 H, CO2H), (1623) 7.9-8.37 (m, 71 1, NH), 7.11 (t, 1H, M i), 6.90-7.05 (s, 2H, CH=CH), 4.35-4.57 (m, 1 f, CH), 3.95-4.20 (m, 2H, CH2), 3.65-3.83 (m, 81 L CH2), 3 ,25-3 ,65 (m, 40H, CH2), 3.23 (s, 3H, OMe), 3.07-3.25 (m, 6H, CH2), 2.20-2.43 (m, 6H, CH2CO). (1624) [00652] ESI MS: C46H77N9Q23 [M+H]+ 1 124.52, found 1124.0,

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2018/98269, 2018, A2 Location in patent: Paragraph 00650-00652

18
[ 955094-26-5 ]
C₁₂₇H₁₉₃F₄N₂₉O₄₆S₂ [ No CAS ]
C₁₄₁H₂₁₁F₄N₃₁O₅₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.05 mg	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.75h;	6.C [00669] Scaffold 24 (3.05 mg) was prepared from compound 23 using the procedure described in Example 2, Part I. ESI MS: C141H211F4N31O52S2: [M+3H]3 3 1 105.17; found 1 105.15.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2018/98269, 2018, A2 Location in patent: Paragraph 00661; 00669

19
[ 57260-73-8 ]
[ 955094-26-5 ]
tert-butyl (16-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4,14-dioxo-7,10-dioxa-3,13-diazahexadecyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In dichloromethane at 10 - 20℃;	2 Example 2 Synthesis of tert-butyl(16-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4,14-dioxo-7,10-dioxa-3,13-diazahexadecyl) carbamate (Compound AA) To a cooled solution of 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate ("maleimide-PEG2-succinimidyl ester", 656 g, 1.54 moles, 1.0 eq) in anhydrous DCM (6.4 kg) is slowly added a solution of tert-butyl (2-aminoethyl)carbamate ("N-BOC-ethylenediamine", 272 g, 1.70 moles, 1.1 eq) in anhydrous DCM (13.5 kg, 2.0 w/w) while maintaining the temperature below 10° C. The reaction mixture was stirred at ambient temperature until RP-HPLC analysis indicated ˜98% conversion to the desired product. The organic phase was washed with water, 10% NaCl solution and concentrated on a rotary evaporator under reduced pressure at 32° C. to approximately 6 volumes. Finally, the title compound was precipitated in EtOAc:heptane (2:1), filtered, washed twice with heptane and subjected to vacuum drying at 25° C. to give 575 g (1.22 moles, 80% yield). ESI-MS: C21H34N4O8 (M+1) 471.3. 1-H-NMR (400 MHz, DMSO d6): δ 8.0 (1H, m), 7.8 (1H, m,), 7.0 (2H, s,), 6.8 (1H, m), 3.6 (4H, m), 3.5 (4H, m), 3.4 (2H, m), 3.3 (2H, m), 3.1 (2H, m), 3.0 (2H, m), 2.3 (4H, m), 1.4 (9H, s). 13C-NMR (400 MHz, DMSO d6): δ 135, 70, 69, 66, 40, 39, 38, 36, 34, 28
	With triethylamine In acetonitrile at 20℃; for 16h;	16 Example 16 Synthesis of Tert-Butyl (16-(2,5-Dioxo-2,5-Dihydro-1H-Pyrrol-1-yl)-4,14-Dioxo-7,10-Dioxa-3,13-Diazahexadecyl)Carbamate (Compound 19) tert-Butyl (2-aminoethyl)carbamate (139.5 mg, 0.138 ml, 0.871 mmol) was added into a solution of 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (compound 18) in 4 ml anhydrous acetonitrile at room temperature, followed by the addition of triethyl amine (88.1 mg, 0.121 ml, 0.871 mmol). The reaction mixture was stirred at room temperature for 16 hours. The mixture was filtered and the filtrate was concentrated under vacuum to give a light yellow oil (compound 19).

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - US2018/369405, 2018, A1 Location in patent: Paragraph 0851-0853
[2]Current Patent Assignee: NOVACYTE THERAPEUTICS - US2019/83634, 2019, A1 Location in patent: Paragraph 0293-0294

20
[ 6066-82-6 ]
[ 756525-98-1 ]
[ 955094-26-5 ]

Yield	Reaction Conditions	Operation in experiment
25%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 2.0h;	The product 2-12 (1.0 g, 3.0 mmol) obtained in the previous step and EDC-HCl (0.69 g, 3.6 mmol) were dissolved in 25 mL DCM, HOSu (0.41 g, 3.6 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. After LCMS showed that the reaction was complete, the reaction mixture was concentrated. The crude product was purified by reversed phase column (TFA 0.05% aqueous solution) to give 0.32 g product as colorless oil, yield 25%. LCMS (ESI) m/z 426.3 (M+H)+.
346 mg	With dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 2.0h;	N-hydroxysuccinimide (105.2 mg, 0.914 mmol) was added into a solution of <strong>[756525-98-1]3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoic acid</strong> (300 mg, 0.914 mmol) in 5 ml anhydrous dichloromethane at room temperature, followed by the addition of N,N'-dicyclohexylcarbodiimide (198 mg, 0.96 mmol). The reaction mixture was stirred for 2 hours at room temperature. The white solid formed was filtered and the filtrate was concentrated under vacuum to give the crude product (compound 18, 346 mg) which was used directly in the next step.

Reference： [1]Patent: US10449258,2019,B2 .Location in patent: Page/Page column 141; 142; 145; 146
[2]Patent: US2019/83634,2019,A1 .Location in patent: Paragraph 0291-0292

21
[ 955094-26-5 ]
N-(2-aminoethyl)-3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanamide trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 16 h / 20 °C 2: dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: NOVACYTE THERAPEUTICS - US2019/83634, 2019, A1

22
[ 955094-26-5 ]
S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl)-L-cysteine trifluoroacetic acid [ No CAS ]
S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl)-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	S-{2-[(3-Aminopropyl){(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine/trifluoroacetic acid (1:1) S-{2-[(3-Aminopropyl){(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine/trifluoroacetic acid (1:1) 30 mg (36 μmol) of S-{2-[(3-aminopropyl){(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-L-cysteine/trifluoroacetic acid (1:1) (Intermediate C71) together with 16.9 mg (40 μmol) of 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-[2-(2-{3-[(2,5-dioxopyrrolidin-1-yl)oxy]-3-oxopropoxy}ethoxy)ethyl]propanamide were initially charged in 1.5 ml of DMF, and 10.9 mg (108 μmol) of 4-methylmorpholine were added. The reaction mixture was stirred at RT overnight, and 7.58 mg (0.13 mmol) of acetic acid were then added. The reaction mixture was purified directly by preparative RP-HPLC (column: Reprosil 250*30; 10μ, flow rate: 50 ml/min, MeCN/water, 0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 33.4 mg (80% of theory) of the compound S-(11-{(1R)-1-[1-benzyl-4-(2, 5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl)-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine. LC-MS (Method 1): Rt=1.34 min; MS (ESIpos): m/z=1027 (M+H)+.
80%	With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	Intermediate F262 Intermediate F262 S-{2-[(3-Aminopropyl){(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine/trifluoroacetic acid (1:1). 30 mg (36 μmol) of 4 S-{2-[(3-aminopropyl){(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-L-cysteine/ trifluoroacetic acid (1:1) (Intermediate C71) together with 16.9 mg (40 μmol) of 5 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-[2-(2-{3-[(2,5-dioxopyrrolidin-1-yl)oxy]-3-oxopropoxy}ethoxy)ethyl]propanamide were initially charged in 1.5 ml of DMF, and 10.9 mg (108 μmol) of 4-methylmorpholine were added. The reaction mixture was stirred at RT overnight, and 7.58 mg (0.13 mmol) of acetic acid were then added. The reaction mixture was purified directly by preparative RP-HPLC (column: Reprosil 25030; 10μ, flow rate: 50 ml/min, MeCN/water, 0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 33.4 mg (80% of theory) of the compound S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl)-N-{3-[2-(2-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethoxy)ethoxy]propanoyl}-L-cysteine. [1265] LC-MS (Method 1): Rt=1.34 min; MS (ESIpos): m/z=1027 (M+H)+.

Reference： [1]Current Patent Assignee: BAYER AG - US2019/77752, 2019, A1 Location in patent: Paragraph 2346-2348
[2]Current Patent Assignee: BAYER AG - US2020/138970, 2020, A1 Location in patent: Paragraph 1263-1265

23
[ 7423-55-4 ]
[ 955094-26-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.5 h / 20 °C / Sealed tube 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 - 25 °C / Large scale 2.2: 20 °C / Large scale 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.5 h / 20 °C 4.1: triethylamine / dichloromethane / 20 - 25 °C 4.2: 20 °C
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 2 h / 20 °C 2: sodium hydrogencarbonate / water; 1,2-dimethoxyethane / 2 h / 20 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: SUZHOU HIGHFINE BIOTECH - CN109608379, 2019, A
[2]Current Patent Assignee: XDCEXPLORER SHANGHAI - US10449258, 2019, B2

24
[ 6066-82-6 ]
C₁₄H₁₉ClN₂O₆ [ No CAS ]
[ 955094-26-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: 1-hydroxy-pyrrolidine-2,5-dione With triethylamine In dichloromethane at 20 - 25℃; Stage #2: C₁₄H₁₉ClN₂O₆ In dichloromethane at 20℃;	4 Specific steps for synthesizing maleimide-dipolyethylene glycol-acrylic succinimide ester: N-hydroxysuccinimide (414.4 g, 3.6 mol) was added to a 10 L three-necked flask.Dichloromethane and triethylamine(607 g, 6.0 mol), stir to room temperature at room temperature, keep the internal temperature not exceeding 25 ° C,The above-prepared acid chloride solution is added dropwise, and after the completion of the dropwise addition, the mixture is stirred at room temperature until the reaction is completed.After treatment, the reaction solution is extracted with water, dried and concentrated.Recrystallization from absolute ethanol gave a white powder (944 g, yield 74%).

Reference： [1]Current Patent Assignee: SUZHOU HIGHFINE BIOTECH - CN109608379, 2019, A Location in patent: Paragraph 0041; 0043; 0044

25
[ 955094-26-5 ]
C₄₉H₅₂N₁₄O₁₀ [ No CAS ]
C₆₃H₇₀N₁₆O₁₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25.2%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 2h;	4.C Part C: To a solution of compound 12 (26 mg, 0.026 mmol in DMF (2.0 ml) was added HOBt (3.88 mg, 0.029 mmol), 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH- pyrrol-l-yl)propanamido)ethoxy)ethoxy)propanoate (12.20 mg, 0.029 mmol), triethylamine (4.0 pL, 0.029 mmol). The mixture was stirred for 2 h at room temperature. The crude product was purified on HPLC (0.1% formic acid 10-90% ACN/water) to afford compound 13 (8.6 mg, 6 58 pmol, 25.2 yield). ESI MS: calc for (%.· 15 CM -,O K, (M+H) 1307.5; found 1306.8.
25.2%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 2h;	To a solution of 60 (26 mg, 0.026 mmol) in DMF (2.0 ml) was added HOBt (3.88 mg, 0.029 mmol), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (12.20 mg, 0.029 mmol), and triethylamine (4.00 µl, 0.029 mmol). The mixture was stirred 2 h at room temp. The crude product was purified on HPLC (0.1 Fomic Acid 10-90% MeCN/Water) to afford 61 (8.6 mg, 6.58 µmol, 25.2 % yield). ESI MS: calc for C49H53N14O10 (M+H) 1307.5; found 1306.8.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/104289, 2019, A1 Location in patent: Paragraph 01075-01077
[2]Thomas, Joshua D.; Yurkovetskiy, Aleksandr V.; Yin, Mao; Bodyak, Natalya D.; Gumerov, Dmitry R.; Tang, Shuyi; Kelleher, Eoin; Jones, Brian D.; Protopopova, Marina; Qin, LiuLiang; Uttard, Alex; Demady, Damon R.; Lowinger, Timothy B. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 72]

26
[ 955094-26-5 ]
C₆₉H₇₁N₁₃O₈ [ No CAS ]
C₈₃H₈₉N₁₅O₁₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.3%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h;	5.F Part F: To a solution of compound 20 (30 mg, 0.025 mmol) in DMF (2 0 mL) was added HOBt (5.02 mg, 0.037 mmol), 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH- pyrrol-l-yl)propanamido)ethoxy)ethoxy)propanoate (15.82 mg, 0.037 mmol), and triethyiamine (5.18 m, 0.037 mmol). The mixture was stirred 16 h at room temperature. The crude product was purified by HPLC (0.1 Formic Acid, 10-90% ACN/Water) to afford the desired MTT- protected maleimide intermediate (28 mg, 0.018 mmol, 74 3 % yield). ESI MS: calc for C83H93N16O14 (M+NH4) 1537.7; found 1537.8.
74.3%	With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h;	To a solution of 67 (30 mg, 0.025 mmol) in DMF (2.0 ml) was added HOBt (5.02 mg, 0.037 mmol), 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (15.82 mg, 0.037 mmol), and triethylamine (5.18 µl, 0.037 mmol). The mixture was stirred 16 h at room temperature at which point LC-MS indicated the reaction was complete. The crude product was purified by HPLC (0.1 Fomic Acid 10-90% MeCN/Water) to afford the desired Mtt-protected maleimide intermediate (28 mg, 0.018 mmol, 74.3 % yield). ESI MS: calc for C83H93N16O14 (M+NH4) 1537.7; found 1537.8.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/104289, 2019, A1 Location in patent: Paragraph 01079; 01084
[2]Thomas, Joshua D.; Yurkovetskiy, Aleksandr V.; Yin, Mao; Bodyak, Natalya D.; Gumerov, Dmitry R.; Tang, Shuyi; Kelleher, Eoin; Jones, Brian D.; Protopopova, Marina; Qin, LiuLiang; Uttard, Alex; Demady, Damon R.; Lowinger, Timothy B. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 72]

27
[ 955094-26-5 ]
C₇₄H₈₀N₁₄O₉ [ No CAS ]
C₈₈H₉₈N₁₆O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53.5%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 1h;	6.D Part D: Compound 26 (6.8 mg, 5.19 pmol) was dissolved in DMF (1 mL), and then triethylamine (0.525 mg, 5.19 pmol) and 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5- dihydro-lH-pyrrol-l-yl)propanamido)ethoxy)ethoxy)propanoate (2.209 mg, 5.19 pmol) vcere added and the mixture stirred at room temperature for 1 hour. The reaction mixture was concentrated on high vacuum and purified on silica gel (0-30% MeOH in DCM) to provide the MTT protected intermediate (4.5 mg, 2.78 pmol, 53.5 % yield). ESI MS: C88H99N16O1.+ (M+H) 1619.8; found 1618 8.
53.5%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 1h;	Compound 73 (6.8 mg, 5.19 µmol) was dissolved in DMF (1 mL), and then triethylamine (0.525 mg, 5.19 µmol) and 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (2.209 mg, 5.19 µmol) were added and the reaction stirred at room temperature for 1 hour. The reaction mixture was concentrated on high vacuum. The crude product was purified on silica gel (0-30% MeOH in DCM) to provide the Mtt protected intermediate 74 (4.5 mg, 2.78 µmol, 53.5 % yield). ESI MS: C88H99N16O15+ (M+H) 1619.8; found 1618.8.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/104289, 2019, A1 Location in patent: Paragraph 01087; 01093
[2]Thomas, Joshua D.; Yurkovetskiy, Aleksandr V.; Yin, Mao; Bodyak, Natalya D.; Gumerov, Dmitry R.; Tang, Shuyi; Kelleher, Eoin; Jones, Brian D.; Protopopova, Marina; Qin, LiuLiang; Uttard, Alex; Demady, Damon R.; Lowinger, Timothy B. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 72]

28
[ 955094-26-5 ]
C₇₈H₈₀N₁₄O₉ [ No CAS ]
C₉₂H₉₈N₁₆O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 0.25h;	7.D Part D: To compound 32 (62 6 mg, 0.046 mmol) was added ETsN (6.43 m, 0.046 mmol), DMF (922 m) and 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanamido)ethoxy)ethoxy)propanoate (19.62 mg, 0.046 mmol), and the mixture was stirred at room temperature for 15 minutes, concentrated on high vacuum, then purified on silica (0-35% MeOH in DCM) to provide the MTT protected intermediate (77 mg, 0.046 mmol, 100 % yield). ESI MS: CV GA i-O,. (M+H) 1667.8; found 1667.7.
100%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 0.25h;	To compound 80 (62.6 mg, 0.046 mmol) was added Et3N (6.43 µl, 0.046 mmol), DMF (922 µl) and 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate (19.62 mg, 0.046 mmol), and the reaction was stirred at room temperature for 15 minutes. The reaction mixture was concentrated on high vacuum, then the crude product was purified on silica (0-35% MeOH in DCM) to provide the Mtt protected intermediate 81 (77 mg, 0.046 mmol, 100 % yield). ESI MS: C92H99N16O15+ (M+H) 1667.8; found 1667.7.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/104289, 2019, A1 Location in patent: Paragraph 01096; 01101
[2]Thomas, Joshua D.; Yurkovetskiy, Aleksandr V.; Yin, Mao; Bodyak, Natalya D.; Gumerov, Dmitry R.; Tang, Shuyi; Kelleher, Eoin; Jones, Brian D.; Protopopova, Marina; Qin, LiuLiang; Uttard, Alex; Demady, Damon R.; Lowinger, Timothy B. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 72]

29
[ 955094-26-5 ]
C₈₂H₁₂₃N₁₇O₂₉ [ No CAS ]
C₉₆H₁₄₁N₁₉O₃₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With triethylamine In 1-methyl-pyrrolidin-2-one; dimethyl sulfoxide at 0 - 20℃;	1.B Part B: To a solution of compound 3 (2.2 mg, 0 377 pmol) in a mixture of NMP (125 pL)/DMSO (50 pL) and TEA (0.166 pL, 1.19 pmol) was added 2,5-dioxopyrrolidin-l -yl 3-(2- (2-(3-(2,5-dioxo-2,5-dihydro-lH-pyrroi-l-yl)propanamido)ethoxy)ethoxy)propanoate (1.0 mg, 2.4 pmol) in NMP (6.5 pL) at 0 °C, and the resulting mixture was stirred at room temperature. After 3 hours additional 2,5-dioxopyrrolidin-l-yi 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanamido)ethoxy)ethoxy)propanoate (2 equivalents) was added and the mixture was stirred overnight. The reaction mixture was neutralized with acetic acid, diluted with water and purified by HPLC (RP Cl 8 column containing 0.1% HOAc (10-7Q%B over 35 min) to afford compound 4 (1 mg, 40% yield). ESI MS calc for C96H143N19Q35 { XI 21 i ) 1061; found 1061.5.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/104289, 2019, A1 Location in patent: Paragraph 01070-10701

30
[ 955094-26-5 ]
C₈₈H₉₄N₁₂O₁₄ [ No CAS ]
C₁₀₂H₁₁₂N₁₄O₂₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In N,N-dimethyl-formamide for 2h; Inert atmosphere;	9.G Part G To a solution of compound 54 (163 pmol) in DCM (18 ml .) was added DABCO (55 mg, 489 mhio) and Pd(PPh3)4 (14 mg, 98 mhio) and the resulting mixture was stirred at room temperature for 0.5 h, then concentrated and purified by chromatography on silica gel (ISCO, 12 g column, 0-5% MeOH/DCM eluent) to afford the desired Alioc/aliyl ester deprotected intermediate as a yellow amorphous solid (1 13 mg, 48 % yield). ESI MS calc for CS8H95N12O14 (M 1 1) 1543.7; found 1543.7. (2063) [01212] To a solution of the Alloc/allyl ester deprotected intermediate (40 mg, 26 mhio) in DMF (1 mL) was added 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH- pyrrol-I-yl)propanarnido)ethoxy)ethoxy)propanoate (12 mg, 29 pmol) and TEA (4.4 pL, 29 mtho) and the mixture was stirred under argon for 2h. The reaction mixture was concentrated to afford crude compound 55 as a yellow oil (60 mg, 100 % yield). ESI MS calc for (2064) C102H113N14O20 (M+H) 1853.8; found 1853.7.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01202; 01211; 01212

31
[ 955094-26-5 ]
C₆₅H₇₁N₁₁O₁₄ [ No CAS ]
C₇₉H₈₉N₁₃O₂₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In N,N-dimethyl-formamide for 2h; Inert atmosphere;	16.C Part C: To a solution of compound 69 (30 mg, 24 pmol) in DMF (1 mL) was added 2,5- dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanamido)ethoxy)ethoxy)propanoate (12 mg, 26 pmol) and TEA (4 pL, 26 pmol). The mixture was stirred under argon for 2 h, concentrated to afford the crude maeimide intermediate as a yellow oil (~40 mg, quant.) ESI MS calc for C79H90N13O20 (M+H) 1540.6; found 1540 5. This material was then dissolved in a mixture of HCOOH (960 pL), THF (160 pL) and w'ater (160 pL) and stirred at room temperature for 1 h, concentrated and then purified by RP-HPLC (ISCO, 10-100 % ACN/water w/ 0.1 % HCOOH eluent) to afford compound 70 as a white, fluffy solid, (17 mg, 51 % yield). ESI MS calc for C-zANnOw (M+H) 1456.6; found 1456.5.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01226; 01228

32
[ 955094-26-5 ]
C₅₁H₅₅N₁₁O₈ [ No CAS ]
C₆₅H₇₃N₁₃O₁₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With triethylamine In N,N-dimethyl-formamide for 1.5h; Inert atmosphere;	7.A To a solution of compound 7 (18 nig, 14 miho) in DMF (1 niL) was added 2,5- dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanamido)ethoxy)ethoxy)propanoate (7 mg, 15 mhio) and TEA (2 pL, 15 miho) and the reaction mixture was stirred under argon for 1.5 h. The mixture was then concentrated under vacuum and purified by chromatography (ISCO RP-HPLC, 5.5 g column, 10-100% ACN/water w/ 0.1 % HCOQH eluent) to afford compound 37 as a tan, fluffy solid (17 mg, 13 mhio, 71 % yield). ESI MS calc for G,4 HX : T)i ·, (M+H) 1260.6; found 1261.4.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01187

33
[ 955094-26-5 ]
C₃₂H₅₇N₉O₂₁ [ No CAS ]
C₄₆H₇₅N₁₁O₂₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70 mg	With triethylamine In N,N-dimethyl-formamide at 20℃; for 2.66667h;	22.E Part E: To a solution of compound 110 (100 mg, 0.111 mmol) in DMF (2 ml) were added 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2, 5-dioxo-2, 5-dihydro- 1 H-pyrrol-1 - yl)propanamido)ethoxy)ethoxy)propanoate (47.1 mg, 0.111 mmol) followed by TEA (0.046 mi, 0 332 mmol). After 2 hoursadditional 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2,5- dihydro-lH-pyrrol-l-yl)propanamido)ethoxy)ethoxy)propanoate 47 1 mg, 0.111 mmol) and TEA (0.046 ml, 0.332 mmoljwas added and the mixture was stirred 40 min. The crude product was purified by RP-HPLC (0.1% HO Ac buffer acetonitrile/ water) to afford compound 111 (70 mg, 52% yield). ESI-MS calc for C46H76N11O27 1214 49; found 1214.45.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01274; 01279

34
[ 955094-26-5 ]
C₃₀H₅₆N₆O₁₅ [ No CAS ]
C₄₄H₇₄N₈O₂₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In N,N-dimethyl-formamide at 20℃; for 4.5h;	25.A A solution of compound 117 (163 mg, 220 pmoi), 2,5-dioxopyrrolidin-l-yl 3-(2- (2-(3-(2,5-dioxo-2, 5-dihydro- 1 H-pyrrol-l-yl)propanamido)ethoxy)ethoxy)propanoate (103 mg, 242 miho), TEA (34 mE, 242 pmoi) and DMF (2 niL) was stirred at room temperature for 4.5 hours. The reaction mixture was concentrated to give the crude compound 120 (250 mg) as an off-white foam that was used in the next step without further purification. ESI MS calc for C44H74N8O21 (M+H) 1051 5; found 1051.4.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01288

35
[ 955094-26-5 ]
C₄₉H₅₁N₁₁O₈ [ No CAS ]
C₆₃H₆₉N₁₃O₁₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With triethylamine In N,N-dimethyl-formamide for 1h; Inert atmosphere;	4.D Part D: To a mixture of compound 24 (34mg, 37pmo) in DMF (1 mL) was added 2,5- di oxopyrrolidin- 1 ~yl 3 -(2-(2-(3 -(2, 5 -di oxo-2, 5 -dihy dro- 1 H-pyrrol - 1 - yl)propanamido)ethoxy)ethoxy)propanoate (17 mg, 41 pmol) and TEA (6 pL, 41 pmol) and the resulting mixture was stirred under argon for 1 h. The reaction mixture was concentrated and purified by HPLC (10-100 % acetonitrile/water containing 0.1% HCOOH eluent), to afford compound 25 as an off-white, fluffy solid (18 mg, 15 pmol, 40 % yield). ESI MS calc for C63H70N13O14 (M+H) 1232.5; found 1232.5.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01171; 01176

36
[ 955094-26-5 ]
C₄₆H₄₆N₁₀O₇ [ No CAS ]
C₆₀H₆₄N₁₂O₁₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With triethylamine In N,N-dimethyl-formamide for 1.25h; Inert atmosphere;	6.D To a solution of compound 34 (16 mg, 19 pmol) in DMF (1 niL) was added 2,5- di oxopyrrolidin- 1 -yl 3 -(2-(2-(3 -(2, 5 -di oxo-2, 5 -dihy dro- 1 H-pyrrol - 1 - yl)propanamido)ethoxy)ethoxy)propanoate (1.1 eqs, 9 mg) and TEA (1.1 eqs, 3 mE) and the resulting mixture was stirred under argon under for 1.25 h. The reaction mixture was concentrated under vacuum and the residue purified by HPLC to afford compound 35 as a fluffy white solid (10 mg, 46% yield). ESI MS calc for CeoHesNnGir (M+H) 1 161.5; found 1161.4

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01182; 01185

37
[ 955094-26-5 ]
C₇₅H₁₀₈N₁₆O₂₄ [ No CAS ]
C₈₉H₁₂₆N₁₈O₃₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With triethylamine In 1-methyl-pyrrolidin-2-one at 0 - 20℃;	1.B To a solution of compound 3 (12 mg, 7.42 mhio) in a mixture of NMP ((5:2 ratio, 50 pL) and TEA (2.068 mE, 0.015 mmol) was added 2,5-dioxopyrrolidin-l ~yl 3-(2-(2-(3-(2,5- dioxo-2,5-dihydro-lH-pyiToi-l-yl)propanamido)ethoxy)ethoxy)propanoate (6.31 mg, 0.015 mmol)) in NMP (50 pL) at 0 °C, and the resulting mixture was stirred at room temperature. (1971) After 4 hours additional 2,5-dioxopyrrolidin--yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-lH-pynOl-l- yl)propanamido)eihoxy)ethoxy)propanoate (0.7 equivalents) was added and the mixture was stirred overnight. The reaction mixture was neutralized with acetic acid, diluted with water and purified by HPLC (RP C18 column containing 0.1% HOAc (10-70%B over 35 min) to afford compound 4 (3 mg, 21% yield) ESI MS calc for CsiH NigCho (M+2H) 964 9, found 964.9

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01154; 01156

38
[ 955094-26-5 ]
C₇₉H₈₅N₁₃O₁₁ [ No CAS ]
C₉₃H₁₀₃N₁₅O₁₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 1h;	8.E Part D: To compound 44 (0.0739 g, 0.049 mmol) was added pyrrolidine (0.012 mL, 0.146 mmol), triphenylphosphine (3.19 mg, 0.012 mmol) and DCM (4.87 mL). To the stirred solution was added PdiPPhOi (5 63 mg, 4.87 pmol), and the reaction was stirred for 1 hour at room temperature. The crude reaction mixture was concentrated and then suspended in DMFiThO (1 : 1, 3 mL). The suspension was centrifuged at 12 G for 14 minutes. The supernatant was filtered and then purified by RP- HPLC (10-90% ACN in H2.O with 0.1% v/v HO Ac) to provide the deprotected intermediate (5.5 mg, 8.1 1 % yield). ESI-MS calc for C^HSONIBQIL (M+H) 1392.7; found 1392.7. (2044) [01 199] To the deprotected intermediate (5.5 mg, 3.95 pmol) were added DMF (0.7 mL), 2,5-dioxopyrrolidin-l-yl 3-(2-(2-(3-(2,5-dioxo-2, 5-dihydro- 1 H-pyrrol-1 - yl)propanamido)ethoxy)ethoxy)propanoate (5.04 mg, 0.012 mmol) and triethylamine (1.651 pL, 0.012 mmol). The reaction mixture v as stirred for 1 hour at room temperature and then concentrated to provide Mtt protected compound 45 (6.73 mg, 100 % yield). ESI-MS calc for C93Hi04Ni5Oi7+ (M+H) 1702 8; found 1702.8. (2045) [01200] To Mtt protected compound 44 (6.73 mg, 3.95 pmol) was added DCM (0.7 mL), 2,2,2-trifluoroethan-l-ol (200 pL, 2745 pmol) and HO Ac (100 m, 1748 mhio) The reaction mixture was stirred at room temperature for 2 hours, and then concentrated. The crude product was purified by RP- PLC (10-90 % ACN in H2O with 0.1 % HCO2H) to provide compound 45 (2 5 mg, 43.8 % yield). ESI-MS calc for ('-d b NVOr (M+H) 1446.7; found 1446.7.

Reference： [1]Current Patent Assignee: MERSANA THERAPEUTICS, INC. - WO2019/126691, 2019, A1 Location in patent: Paragraph 01189; 01198-01200

39
[ 955094-26-5 ]
C₃₅H₄₉ClN₂O₁₁S [ No CAS ]
C₅₃H₇₂ClN₅O₂₀S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	In aq. phosphate buffer; N,N-dimethyl-formamide at 20℃;	12 Synthesis of Compound XDCE-M-001 Compound 9-7 (40 mg, 0.054 mmol) was dissolved in 4 mL DMF, 0.2 mL pH=6 potassium phosphate buffer and CE-L-071 (115 mg, 0.27 mmol) were added, the mixture was stirred overnight at room temperature under nitrogen atmosphere. The reaction mixture was filtered, purified directly by prep-HPLC to give 37 mg product XDCE-M-001 as white solid, yield 59%. LCMS (ESI) m/z 627.8 (M/2+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 6.87 (br, 1H), 6.85 (s, 1H), 6.78 (s, 1H), 6.74 (br, 1H), 6.41 (t, J=13.2 Hz, 1H), 6.19 (d, J=10.8 Hz, 1H), 5.61-5.53 (m, 1H), 4.92 (d, J=11.2 Hz, 1H), 4.30 (q, J=10.4 Hz, 1H), 4.15 (q, J=7.6 Hz, 1H), 3.99 (s, 3H), 4.04-3.96 (m, 1H), 3.87-3.76 (m, 6H), 3.70-3.60 (m, 6H), 3.56-3.42 (m, 9H), 3.36 (s, 3H), 3.20 (d, J=10.8 Hz, 2H), 3.15 (s, 3H), 2.92-2.85 (m, 8H), 2.62-2.50 (m, 4H), 2.23 (d, J=14.4 Hz, 1H), 1.69 (s, 3H), 1.51-1.48 (m, 3H), 1.30-1.25 (m, 6H), 0.83 (s, 3H).

Reference： [1]Current Patent Assignee: XDCEXPLORER SHANGHAI - US10449258, 2019, B2 Location in patent: Page/Page column 141-144; 147; 148

40
[ 55750-62-4 ]
[ 955094-26-5 ]

Reference： [1]Patent: US10449258,2019,B2

41
[ 955094-26-5 ]
[ 51649-83-3 ]
N-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)-3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With triethylamine In N,N-dimethyl-formamide for 48h;

Reference： [1]Current Patent Assignee: DANA-FARBER CANCER INSTITUTE - WO2019/236522, 2019, A1 Location in patent: Paragraph 0112; 0183

42
[ 955094-26-5 ]
C₃₀H₄₁N₉O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 23 °C 2: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 36 h / 23 °C 3: hydrogenchloride / 1,4-dioxane / 6 h / 23 °C

Reference： [1]Collins, Jeffrey; Gamache, Raymond F.; Murphy, Jennifer M.; Tsai, Wen-Ting K.; Wu, Anna M.; Zettlitz, Kirstin A. [Chemical Science, 2020, vol. 11, # 7, p. 1832 - 1838]

43
[ 955094-26-5 ]
C₃₅H₄₉N₉O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 23 °C 2: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 36 h / 23 °C

Reference： [1]Collins, Jeffrey; Gamache, Raymond F.; Murphy, Jennifer M.; Tsai, Wen-Ting K.; Wu, Anna M.; Zettlitz, Kirstin A. [Chemical Science, 2020, vol. 11, # 7, p. 1832 - 1838]

44
[ 955094-26-5 ]
C₄₆H₆₇N₁₃O₁₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 23 °C 2: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 36 h / 23 °C 3: hydrogenchloride / 1,4-dioxane / 6 h / 23 °C 4: triethylamine / N,N-dimethyl-formamide / 16 h / 23 °C

Reference： [1]Collins, Jeffrey; Gamache, Raymond F.; Murphy, Jennifer M.; Tsai, Wen-Ting K.; Wu, Anna M.; Zettlitz, Kirstin A. [Chemical Science, 2020, vol. 11, # 7, p. 1832 - 1838]

45
[ 955094-26-5 ]
[ 13734-28-6 ]
C₂₅H₄₀N₄O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 23℃; for 16h;

Reference： [1]Collins, Jeffrey; Gamache, Raymond F.; Murphy, Jennifer M.; Tsai, Wen-Ting K.; Wu, Anna M.; Zettlitz, Kirstin A. [Chemical Science, 2020, vol. 11, # 7, p. 1832 - 1838]

46
[ 955094-26-5 ]
C₂₂H₂₀FN₃O₄ [ No CAS ]
C₁₄H₂₆N₄O₆ [ No CAS ]
C₅₀H₆₂FN₉O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	Stage #1: 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-[2-(2-{3-[(2,5-dioxopyrrolidin-1-yl)oxy]-3-oxopropoxy}ethoxy)ethyl]propanamide; C₁₄H₂₆N₄O₆ In N,N-dimethyl-formamide at 20℃; for 15h; Stage #2: C₂₂H₂₀FN₃O₄ With 4-methyl-morpholine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In water; N,N-dimethyl-formamide at 20℃; for 1.5h;	20 22e: The solution of compound 18c (15.2 mg, 0.035 mmol) in methanol (2 mL) was added Pd (10% on carbon, 3.7 mg, 0.0035 mmol) and the reaction flask was purged with hydrogen. It was hydrogenated with a hydrogen balloon at room temperature for 3 hours and then filtered. The filtrate was stripped to give compound 19c as a colorless foam. It was dissolved in anhydrous DMF (0.3 mL) and 13d (15.9 mg, 0.03 mmol) was added. The obtained colorless clear solution was stirred at room temperature for 15 hours. It was diluted with DMF (0.2 mL) followed by addition of 6a (15.3 mg, 0.037 mmol) and NMM (4.1µL, 0.037 mmol). DMTMM (20.7 mg, 0.075 mmol) in deionized water (0.1 mL) was then added and the reaction solution was stirred at room temperature for 1.5 hours. The reaction mixture was stripped under reduced pressure and the residue was purified by silica gel chromatography (CH2Cl2/MeOH, 0 to 20% MeOH) to give desired 22e (10 mg, yield 26%). MS (ESI): m/z 1049.1 (M + H)+, 1093.2 (M + HCOOH - H)-.

Reference： [1]Current Patent Assignee: IMMUNOGEN INC - WO2020/219287, 2020, A1 Location in patent: Paragraph 00430

47
[ 955094-26-5 ]
N-(2-aminoethyl)-4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy)butanamide [ No CAS ]
N-(16-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4,14-dioxo-7,10-dioxa-3,13-di- azahexadecyl)-4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy) butanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With N-ethyl-N,N-diisopropylamine at 20℃;	3.1.7. Synthesis of N-(16-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4,14-dioxo-7,10-dioxa-3,13-di- azahexadecyl)-4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy) butanamide (9b) Compound 9b was synthesized by employing the experimental protocolsdescribed for 9a. The yield was 51% as a light yellow solid. 1HNMR (400 MHz, DMSO-d6) δ 8.04 (t, J = 5.6 Hz, 1H), 7.90 (s, 2H), 7.52(s, 1H), 7.35 (s, 1H), 7.00 (s, 2H), 5.49 (d, J = 4.4 Hz, 1H), 5.28 - 5.22(m, 1H), 4.03 (t, J = 6.4 Hz, 2H), 3.90 (s, 3H), 3.60 - 3.56 (m, 4H), 3.46(d, J = 2.8 Hz, 4H), 3.40 - 3.37 (m, 2H), 3.15 - 3.11 (m, 2H), 3.08 - 3.07(m, 4H), 2.34 - 2.27 (m, 4H), 2.25 - 2.21 (m, 2H), 1.98 - 1.93 (m, 2H),1.36 (d, J = 6.2 Hz, 3H). ESI m/z (M + H)+ calculated for C29H42N5O12 +652.28; found 652.29

Reference： [1]Li, Jiaguo; Xiao, Dian; Xie, Fei; Li, Wei; Zhao, Lei; Sun, Wei; Yang, Xiaohong; Zhou, Xinbo [Bioorganic Chemistry, 2021, vol. 111]

48
[ 955094-26-5 ]
C₂₃H₃₇N₅O₁₀ [ No CAS ]
C₃₈H₅₆N₆O₁₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; for 16h;	3 Synthesis of linker molecule 3: Linker molecule 1 (1 mmol, 534 mg) was dissolved in DMF (10 ml) and N-methylmorpholine (1.2 ml). To this solution a solution of maleimide-PEG2- succinimidyl ester 2 (Sigma Aldrich 746223) (1.1 mmol (468 mg)) in DMF (10 ml) was added slowly and then stirred for 16 h at ambient temperature. The solvent was removed under vacuum. The residue was acidified by addition of 1 M HC1 and the product was extracted with ethyl acetate. The combined organic layers were washed with water and brine und dried (Na2S04). The solvent was removed under reduced pressure and the crude product (0.8 g) was used in the next step.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2021/123074, 2021, A1 Location in patent: Paragraph 0330-0331; 0334-0335

49
[ 955094-26-5 ]
Phe-Arg-Arg-Gly [ No CAS ]
maleimide-PEG₂-FRRG-COOH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide at 37℃; for 12h;

Reference： [1]Ahn, Cheol-Hee; Byun, Youngro; Cho, Hanhee; Kim, Jinseong; Kim, Kwangmeyung; Moon, Yujeong; Shim, Man Kyu; Song, Sukyung; Yang, Suah [Pharmaceutics, 2022, vol. 14, # 1]

50
[ 955094-26-5 ]
C₁₃₃H₂₆₅N₅O₅₀*ClH [ No CAS ]
C₁₄₇H₂₈₃N₇O₅₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 20℃;	To a solution of compound 7 (78 mg, 0.0281 mmol, 1.0 equiv.) and compound 8 (12 mg, 0.0281 mmol, 1.0 equiv.) in anhydrous DCM (2 mL) was added triethylamine (0.020 mL, 0.140 mmol, 5.0 equiv.) at room temperature. The reaction mixture was kept at room temperature overnight and the solvent was concentrated. LP101-p was separated by CombiFlash eluting with 12-20% methanol in dichloromethane. LC-MS: calculated [M+3H]/3 1015.31, found 1015.71.
	With triethylamine In dichloromethane at 20℃;	To a solution of compound 7 (78 mg, 0.0281 mmol, 1.0 equiv.) and compound 8 (12 mg, 0.0281 mmol, 1.0 equiv.) in anhydrous DCM (2 mL) was added triethylamine (0.020 mL, 0.140 mmol, 5.0 equiv.) at room temperature. The reaction mixture was kept at room temperature overnight and the solvent was concentrated. LP101-p was separated by CombiFlash eluting with 12-20% methanol in dichloromethane. LC-MS: calculated [M+3H]/31015.31, found 1015.71.

Reference： [1]Current Patent Assignee: ARROWHEAD RESEARCH CORP - WO2022/56273, 2022, A1 Location in patent: Paragraph 0551
[2]Current Patent Assignee: ARROWHEAD RESEARCH CORP - WO2022/56277, 2022, A1 Location in patent: Paragraph 0617

51
[ 955094-26-5 ]
C₈₂H₁₁₁N₂₁O₂₃S₂ [ No CAS ]
C₉₆H₁₂₉N₂₃O₂₉S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 5h;	7 Preparation of L6Orn-carbonate-maleimide: DIEA (1.9 μL, 10.8 pmol, 4.0 eq.) was added to a solution of 2,5-dioxopyrrolidin-1 -yl (0438) 3-(2-(2-(3-(2,5-dioxo-2h-pyrrol-1 (5h)-yl)propanamido)ethoxy)ethoxy)propanoate (1 .2 mg, 2.7 pmol, 1.0 eq.) and L6Orn-carbonate-NH2 (5.0 mg, 2.7 pmol, 1.0 eq.) in DMF (0.1 mL) at rt. After stirring at rt for 2 h, more of 2,5-dioxopyrrolidin-1 -yl 3-(2-(2-(3- (2,5-dioxo-2h-pyrrol-1(5h)-yl)propanamido)ethoxy)ethoxy)propanoate (1.2 mg, 2.7 µmol, 1.0 eq.) in DMF (50 µL) was added to the reaction mixture. After stirring at rt for 3 h, TFA (4 mL) was added to the reaction mixture. Purification on C18 (12 g, 10 to 50% of ACN+0.1%TFA in water+0.1%TFA over 12 CV) afforded L6Orn-carbonate- maleimide (1.6 mg, 0.7 µmol, UV purity 91%, 25% yield) as a white powder after freeze-drying. UPLC-MS (method 4): Rt = 2.07 min, m/z = 1067 [M+2H]2+, 1065 [M- 2H]2-.

Reference： [1]Current Patent Assignee: DEBIOPHARM RES MANUFACTURING - WO2022/79031, 2022, A1 Location in patent: Page/Page column 244-245

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	955094-26-5	MDL No. :	MFCD11041137
Formula :	C₁₈H₂₃N₃O₉	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	TZPDZOJURBVWHS-UHFFFAOYSA-N
M.W :	425.39	Pubchem ID :	51340948
Synonyms :		Chemical Name :	2,5-Dioxopyrrolidin-1-yl 3-(2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethoxy)ethoxy)propanoate

Num. heavy atoms :	30
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.56
Num. rotatable bonds :	15
Num. H-bond acceptors :	9.0
Num. H-bond donors :	1.0
Molar Refractivity :	104.82
TPSA :	148.62 Å²

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-10.76 cm/s

Log Po/w (iLOGP) :	2.58
Log Po/w (XLOGP3) :	-2.63
Log Po/w (WLOGP) :	-2.31
Log Po/w (MLOGP) :	-1.44
Log Po/w (SILICOS-IT) :	0.19
Consensus Log Po/w :	-0.72

[ CAS No. 955094-26-5 ] {[proInfo.proName]}

Quality Control of [ 955094-26-5 ]

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Product Details of [ 955094-26-5 ]

Calculated chemistry of [ 955094-26-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 955094-26-5 ]

Application In Synthesis of [ 955094-26-5 ]

[ 955094-26-5 ] Synthesis Path-Downstream 1~51

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	1.0
Ghose :	None
Veber :	2.0
Egan :	1.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	0.17
Solubility :	628.0 mg/ml ; 1.48 mol/l
Class :	Highly soluble
Log S (Ali) :	0.06
Solubility :	485.0 mg/ml ; 1.14 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-2.17
Solubility :	2.9 mg/ml ; 0.00681 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.8

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

Precautionary Statements-General
Code	Phrase
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Prevention
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Code	Phrase
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P321
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P342	If experiencing respiratory symptoms:
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P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
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P361	Remove/Take off immediately all contaminated clothing.
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P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
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P411
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P413
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P422
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P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling