Name: 629626-40-0|tert-Butyl (2-(2-iodoethoxy)ethyl)carbamate|95%
Brand: Ambeed
SKU: A1161790
Price: 81.0 USD
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1
[ 24424-99-5 ]
[ 111-46-6 ]
[ 629626-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: di-<i>tert</i>-butyl dicarbonate; diethylene glycol With potassium hydroxide Stage #2: With methanesulfonyl chloride; triethylamine Stage #3: With sodium iodide	D Example D Synthesis of [ (7R) -7- [ (Z)-2- (2-AMINO-5-CHLOROTHIAZOL-4-YL)-2- (2- (2-] aminoethoxy) ethoxyimino) [ACETAMIDO]-3- [ (1-PYRIDINIO) METHYL]-3-CEPHEM-4-] carboxylate bis-Trifluoroacetic Acid Salt The procedure of Example A was used, except that the following procedure was substituted for Step 2: Step 2-Preparation of Ethyl [(Z)-2-(2-TRIPHENYLMETHYLAMINOTHIAZOL-4] [2-[2-(2-N-BOC-AMINOETHYL . ETHOXVIMINO] ACETATE] (i. e, ethyl ester of Compound 6a where R1 is -(CH2)-O-(CH2)2-, R2 is hydrogen, R14 is triphenylmethyl, R'6 is BOC, and A is [HVDROSEN)] The intermediate from Step 1 in Example A (42.5 g, 86 mmol) was added to a stirred suspension o N-BOC-2-(2-iodoethoxy)-ethylamine (28.5 g, 90 mmol) (prepared in three steps from 2- (2-hydroxyethoxy) ethanol, i. e. , (i) BOC2O, KOH, (ii) MsCl, Et3N and (iii) NaI) and cesium carbonate (84.1 g, 258 mmol) in DMF (300 mL). The suspension was stirred for 16 h at room temperature at which time HPLC indicated that the reaction was complete. The reaction mixture was then filtered and the filter cake washed with DMF (100 mL). The filtrate was diluted with ethyl acetate [(1] L) and washed with water (300 mL), IN [HCL] (200 mL), saturated aqueous sodium bicarbonate (200 mL) and brine (200 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (ethyl acetate: hexane, 1: 1) to afford 49.7g (90% yield) of the title intermediate as an off-white solid. 'H NMR (DMSO-d6, 300 MHz) [: No. = ]2.96 (s, broad, 2H), 3.20-3. 55 (q, 2H), 3.59 (t, 2H), 3.70 (t, 2H), 4.19 (t, 2H), 5.13 (d, 1H), 5.31-5. 64 (q, 2H), 5.80 (dd, 1H), 7.40 (s, 2H), 7.87 (s, broad, 3H), 8.20 (t, 2H), 8.64 (t, 1H), 9.23 (d, 2H), 9. [55] (d, [1H).] MS [M/Z] : 503.1 [M - pyridine]+.

Reference： [1]Current Patent Assignee: THERAVANCE BIOPHARMA, INC. - WO2003/99858, 2003, A1 Location in patent: Page 43

2
[ 629626-40-0 ]
[ 629626-41-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With caesium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;	D Example D Synthesis of [ (7R) -7- [ (Z)-2- (2-AMINO-5-CHLOROTHIAZOL-4-YL)-2- (2- (2-] aminoethoxy) ethoxyimino) [ACETAMIDO]-3- [ (1-PYRIDINIO) METHYL]-3-CEPHEM-4-] carboxylate bis-Trifluoroacetic Acid Salt The procedure of Example A was used, except that the following procedure was substituted for Step 2: Step 2-Preparation of Ethyl [(Z)-2-(2-TRIPHENYLMETHYLAMINOTHIAZOL-4] [2-[2-(2-N-BOC-AMINOETHYL . ETHOXVIMINO] ACETATE] (i. e, ethyl ester of Compound 6a where R1 is -(CH2)-O-(CH2)2-, R2 is hydrogen, R14 is triphenylmethyl, R'6 is BOC, and A is [HVDROSEN)] The intermediate from Step 1 in Example A (42.5 g, 86 mmol) was added to a stirred suspension o N-BOC-2-(2-iodoethoxy)-ethylamine (28.5 g, 90 mmol) (prepared in three steps from 2- (2-hydroxyethoxy) ethanol, i. e. , (i) BOC2O, KOH, (ii) MsCl, Et3N and (iii) NaI) and cesium carbonate (84.1 g, 258 mmol) in DMF (300 mL). The suspension was stirred for 16 h at room temperature at which time HPLC indicated that the reaction was complete. The reaction mixture was then filtered and the filter cake washed with DMF (100 mL). The filtrate was diluted with ethyl acetate [(1] L) and washed with water (300 mL), IN [HCL] (200 mL), saturated aqueous sodium bicarbonate (200 mL) and brine (200 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (ethyl acetate: hexane, 1: 1) to afford 49.7g (90% yield) of the title intermediate as an off-white solid. 'H NMR (DMSO-d6, 300 MHz) [: No. = ]2.96 (s, broad, 2H), 3.20-3. 55 (q, 2H), 3.59 (t, 2H), 3.70 (t, 2H), 4.19 (t, 2H), 5.13 (d, 1H), 5.31-5. 64 (q, 2H), 5.80 (dd, 1H), 7.40 (s, 2H), 7.87 (s, broad, 3H), 8.20 (t, 2H), 8.64 (t, 1H), 9.23 (d, 2H), 9. [55] (d, [1H).] MS [M/Z] : 503.1 [M - pyridine]+.

Reference： [1]Current Patent Assignee: THERAVANCE BIOPHARMA, INC. - WO2003/99858, 2003, A1 Location in patent: Page 43-44

3
[ 139115-91-6 ]
[ 603-35-0 ]
[ 629626-40-0 ]
[ 791-28-6 ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-imidazole; iodine In dichloromethane at 0 - 20℃;	10.A A portion of the oil (10.0 g, 48.7 mmol) was treated with triphenylphosphine (15.33 g, 58.45 mmol), imidazole (4.64 g,68.2 mmol), and iodine (16.01 g, 63.3 mmol) according to the method described in Part B of Example 4, with the modification that dichloromethane (325 mL) was used instead of diethyl ether and acetonitrile, to provide 7.82 g of ført-butyl 2-(2- iodoethoxy)ethylcarbamate containing a small amount of triphenylphosphine oxide.

Reference： [1]Current Patent Assignee: 3M CO - WO2006/86449, 2006, A2 Location in patent: Page/Page column 98

4
[ 629626-40-0 ]
[ 905926-02-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 7-hydroxy-2-propylthiazolo[4,5-c]quinoline With caesium carbonate In N,N-dimethyl-formamide at 75℃; for 0.5h; Stage #2: 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane In N,N-dimethyl-formamide at 75℃; for 3.75h;	10.B Under a nitrogen atmosphere, cesium carbonate (1.50 g, 4.61 mmol) was added to a suspension of 2-propyl[l,3]thiazolo[4,5-c]quinolin-7-ol (0.75 g, 3.1 mmol) in DMF (15 mL), and the reaction mixture was heated at 75 °C for 30 minutes. A solution of tert-bxxtyl 2-(2-iodoethoxy)ethylcarbamate (1.93 g, 6.14 mmol) in DMF (5 mL) was added dropwise with stirring. The reaction mixture was stirred at 75 °C for 3.75 hours. The solvent was then removed under reduced pressure at 65 0C. The resulting solid was partitioned between dichloromethane (100 mL) and water (100 mL). The organic layer was washed sequentially with water (50 mL) and brine (50 mL), dried over magnesium sulfate; filtered, and concentrated under reduced pressure. The resulting dark brown solid was purified by column chromatography using a HORIZON HPFC system (silica cartridge, eluting with 0 to 8% CMA in chloroform), and the purified product was dried under high vacuum to provide 1.31 g of tert-butyl 2-{2-[(2-propyl[l,3]thiazolo[4,5-c]quinolin-7- yl)oxy]ethoxy}ethylcarbamate as a light yellow solid.

Reference： [1]Current Patent Assignee: 3M CO - WO2006/86449, 2006, A2 Location in patent: Page/Page column 99

5
[ 139115-91-6 ]
[ 629626-40-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;
98%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; Cooling with ice;	1.2 Step 2 Add II-1 (1.5mmol) and elemental iodine (1.8mmol) into 10mL of dichloromethane,After stirring thoroughly, triphenylphosphine (2 mmol) and imidazole (2 mmol) and the mixture dissolved in 10 mL of dichloromethane were added dropwise under an ice bath.As the reaction progresses, the iodine in the reaction solution gradually dissolves to form a creamy yellow suspension.After the addition is complete, remove the ice bath and stir at room temperature overnight. After the reaction is over, add 10 mL of ethyl acetate and 10 mL of 10% sodium thiosulfate aqueous solution to the reaction solution, and separate the organic phase and the aqueous phase with a separatory funnel.The aqueous phase was extracted three times with 10 mL of ethyl acetate and combined with the previous organic phase.The combined organic phase was washed successively with saturated sodium bicarbonate and saturated sodium chloride solution, and dried with anhydrous sodium sulfate.The dried organic phase was concentrated under reduced pressure, and the mixture was subjected to column chromatography to obtain a colorless oily substance tert-butoxyyl 2-(2-iodoalkoxy)ethylamine III-1 (n=1),Yield: 98%.
98%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 20℃; for 20h;	Tert-butyl (2-(2-iodoethoxy)ethyl)carbamate (H) To a solution of tert- butyl (2-(2-hydroxyethoxy)ethyl)carbamate (CAS No. 139115- 91-6) (5.2 g, 25.36 mmol) in DCM (60 mL) at room temperature was added triphenyl phosphine (7.98 g, 30.43 mmol) and imidazole (0.569 g, 8.36 mmole). The reaction mixture was cooled to 0°C. Iodine (8.36 g, 32.92 mmol) was added portion-wise to the reaction mixture at 0°C. The reaction mixture was slowly warmed to room temperature and stirred for 20 h. The reaction mixture was poured into water (100 mL) and extracted with DCM (3 x 50 mL). The combined organic layer was dried over sodium sulphate, filtered and concentrated under reduce pressure. The crude material was added diethyl ether (100 mL) and the resulting precipitate was filtered and washed with diethyl ether (3 x 50 mL). The combined filtrate was concentrated under reduced pressure and the crude material was purified by column chromatography (silica gel, eluting with 20% (v/v) ethyl acetate in hexane) yielding tert-butyl (2-(2-iodoethoxy)ethyl)carbamate (H) as a colorless oil. (7.8 g, 98%). [00178] LCMS (Method B): 2.254 min, MS: ES+ 316.13 (M+1); 1H NMR (DMSO-d6,400 MHz): d 1.36 (s, 9H), 3.04 - 3.08 (m, 2H), 3.30 (t, J = 6.4Hz, 2H), 3.40 (t, J = 6.4Hz, 2H), 3.62 (t, J = 6.4Hz, 2H), 6.08 (s, 1H).

96%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 20℃; Inert atmosphere;	tert-Butyl [2-(2-iodoethoxy)ethyl]carbamate (65) To a cold (at 0 °C) well-stirred solution of ieri-butyl [2-(2-hydroxyethoxy)ethyl]carbamate (2.50 g, 12.2 mmol), triphenylphosphine (3.82 g, 14.6 mmol) and imidazole (0.99 g, 14 mmol) in DCM (50 mL) under nitrogen was added solid iodine (3.39 g, 13.4 mmol). The iodine slowly dissolved leaving a milky yellow suspension. The ice bath was removed and the reaction allowed to warm to rt and stir overnight. The reaction was partitioned between ethyl acetate and 10% sodium thiosulfate solution (lOOmL each), the layers were separated and the aqueous layer was extracted with ethyl acetate (3x 50mL). The organics were combined, washed with saturated sodium bicarbonate and brine, dried with anhydrous sodium sulfate and concentrated. The residue was subjected to silica gel chromatography (BDH, 230-400 mesh, 200 g, elution with 0, 5, 10 , 15 and 20% ethyl acetate/hexane) to give 3.69g (96%) of tert- butyl [2-(2-iodoethoxy)ethyl]carbamate as a clear colorless oil. FontWeight="Bold" FontSize="10" H NMR (300 MHz, CDC13) δ ppm 1.45 (s, 9 H) 3.23 - 3.30 (m, 2 H) 3.30 - 3.40 (m, 2 H) 3.52 - 3.60 (m, 2 H) 3.68 - 3.77 (m, 2 H) 4.94 (br. s., 1 H); HPLC Retention Time: 3.56 min. MS (ESI+) for C9H18IN03 m/z 337.9 (M+Na)+.
95%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; for 1.5h;	1 2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane 2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane Triphenylphosphine (2.87 g, 10.94 mmol) and imidazole (0.75 g, 11.02 mmol) were dissolved in dichloromethane (15 ml), and the solution was stirred for 5 minutes. Then, iodine (2.78 g, 10.95 mmol) was added thereto, and the mixture was stirred for 10 minutes. A dichloromethane (4 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-ethanol (1.5 g, 7.308 mmol) was added dropwise thereto, and the mixture was stirred at room temperature for 1.5 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was filtered through celite, and a 5% aqueous sodium thiosulfate solution was added to the filtrate to remove iodine. The organic layer was washed twice with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=85:15) to obtain 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (2.19 g, yield: 95%).
95%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; for 1.5h; Inert atmosphere;	1 2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane 2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane Triphenylphosphine (2.87 g, 10.94 mmol) and imidazole (0.75 g, 11.02 mmol) were dissolved in dichloromethane (15 ml), and the solution was stirred for 5 minutes. Then, iodine (2.78 g, 10.95 mmol) was added thereto, and the mixture was stirred for 10 minutes. A dichloromethane (4 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-ethanol (1.5 g, 7.308 mmol) was added dropwise thereto, and the mixture was stirred at room temperature for 1.5 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was filtered through celite, and a 5% aqueous sodium thiosulfate solution was added to the filtrate to remove iodine. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=85:15) to obtain 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (2.19 g, yield: 95%).
95%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; for 1.5h; Inert atmosphere;	1 2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane Triphenylphosphine (2.87 g, 10.94 mmol) and imidazole (0.75 g, 11.02 mmol) were dissolved in dichloromethane (15 ml), and the solution was stirred for 5 minutes. Then, iodine (2.78 g, 10.95 mmol) was added thereto, and the mixture was stirred for 10 minutes. A dichloromethane (4 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-ethanol (1.5 g, 7.308 mmol) was added dropwise thereto, and the mixture was stirred at room temperature for 1.5 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was filtered through celite, and a 5% aqueous sodium thiosulfate solution was added to the filtrate to remove iodine. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=85:15) to obtain 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (2.19 g, yield: 95%).
95%	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; for 1.5h; Inert atmosphere;	1 2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane Triphenylphosphine (2.87 g, 10.94 mmol) and imidazole (0.75 g, 11.02 mmol) were dissolved in dichloromethane (15 ml), and the solution was stirred for 5 minutes. Then, iodine (2.78 g, 10.95 mmol) was added thereto, and the mixture was stirred for 10 minutes. A dichloromethane (4 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-ethanol (1.5 g, 7.308 mmol) was added dropwise thereto, and the mixture was stirred at room temperature for 1.5 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was filtered through celite, and a 5% aqueous sodium thiosulfate solution was added to the filtrate to remove iodine. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=85:15) to obtain 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (2.19 g, yield: 95%).
89%	With 1H-imidazole; iodine; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
	With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 20℃; for 20h;	141.i (i) Production of tert-butyl [2- (2- iodoethoxy) ethyl] carbamateTo a solution of tert-butyl [2-(2- hydroxyethoxy) ethyl] carbamate (2.1 g) , triphenylphosphine (3.21 g) and imidazole (0.83 g) in dichloromethane- (40 mL) was added iodine (2.85 g) at 00C. The mixture was stirred at room temperature for 20 hr . Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was 5 washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Diethyl ether was added to the residue, and the precipitated crystals were removed by filtration. The filtrate was concentrated, and the residue was10 separated and purified by column chromatography (eluent, hexanerethyl acetate = 9:1→3:1) to give the title compound (2.55 g) as a colorless oil.1H-NMR (CDCl3) δ: 1-45 (9H, s), 3.26 (2H, t, J = 6.6 Hz), 3.30-3.35 (2H, m) , 3.55 (2H, t, J = 5.3 Hz), 3.71 (2H,15 t, J = 6.6 Hz), 4.83-5.01 (IH, m) .
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 16 h / 0 - 20 °C 2: sodium iodide / propan-2-one / 65 °C

Reference： [1]Meng, Qingqing; Wang, Zengtao; Cui, Jiahua; Cui, Qing; Dong, Jinyun; Zhang, Qijing; Li, Shaoshun [Journal of Medicinal Chemistry, 2018, vol. 61, # 23, p. 10901 - 10909]
[2]Current Patent Assignee: SHANGHAI JIAO TONG UNIVERSITY - CN110396403, 2020, B Location in patent: Paragraph 0036; 0039
[3]Current Patent Assignee: NEOPHORE - WO2021/148786, 2021, A1 Location in patent: Paragraph 00177-00178
[4]Current Patent Assignee: GENCIA CORPORATION - WO2014/144017, 2014, A2 Location in patent: Paragraph 0347
[5]Current Patent Assignee: TOHOKU UNIVERSITY - US2015/353489, 2015, A1 Location in patent: Paragraph 0098; 0175; 0176
[6]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2019/224165, 2019, A1 Location in patent: Paragraph 0093; 0094; 0153-0154
[7]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1 Location in patent: Paragraph 0084-0085; 0146-0147
[8]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1 Location in patent: Paragraph 0084-0085; 0146-0147
[9]Heller, Katharina; Ochtrop, Philipp; Albers, Michael F.; Zauner, Florian B.; Itzen, Aymelt; Hedberg, Christian [Angewandte Chemie - International Edition, 2015, vol. 54, # 35, p. 10327 - 10330][Angew. Chem., 2015, vol. 35, # 37, p. 10467 - 10471,5]
[10]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2007/97470, 2007, A2 Location in patent: Page/Page column 245-246
[11]Current Patent Assignee: MERCK & CO INC - WO2018/57409, 2018, A1

6
[ 629626-40-0 ]
[ 603-35-0 ]
10,10-dimethyl-8-oxo-1,1,1-triphenyl-4,9-dioxa-7-aza-1-phosphoniaundecane iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	In ethyl acetate for 72h; Inert atmosphere; Reflux;	10,10-Dimethyl-8-oxo-1,1,1-triphenyl-4,9-dioxa-7-aza-1-phosphoniaundecane iodide (66) To a well-stirred solution of ieri-butyl [2-(2-iodoethoxy)ethyl]carbamate (3.69 g, 11.7 mmol) in ethyl acetate (60 mL) was added triphenylphosphine (3.378 g, 12.88 mmol). The reaction was brought to reflux under nitrogen for 72h. The reaction mixture was cooled to rt, and the product crystallized on standing. The solid was collected, washed with ethyl acetate and air dried to give 4.97g (73%) of 10,10-dimethyl-8-oxo- 1,1,1 -triphenyl-4, 9-dioxa- 7-aza-l-phosphoniaundecane iodide as a white solid. 1H NMR (300 MHz, DMSO-33NO3P m/z 450.0 (M)+ .

Reference： [1]Current Patent Assignee: GENCIA CORPORATION - WO2014/144017, 2014, A2 Location in patent: Paragraph 0366

7
[ 24424-99-5 ]
[ 629626-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 2 h / 20 °C 2: 1H-imidazole; triphenylphosphine; iodine / tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: methanol / 2 h / 20 °C 2: triphenylphosphine; 1H-imidazole; iodine / dichloromethane / 1.5 h / 20 °C
	Multi-step reaction with 2 steps 1: dichloromethane / 12 h / 0 - 20 °C 2: triphenylphosphine; 1H-imidazole; iodine / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere

Multi-step reaction with 2 steps 1: dichloromethane / 20 °C / Cooling with ice 2: iodine; triphenylphosphine; 1H-imidazole / dichloromethane / 20 °C / Cooling with ice

Reference： [1]Heller, Katharina; Ochtrop, Philipp; Albers, Michael F.; Zauner, Florian B.; Itzen, Aymelt; Hedberg, Christian [Angewandte Chemie - International Edition, 2015, vol. 54, # 35, p. 10327 - 10330][Angew. Chem., 2015, vol. 35, # 37, p. 10467 - 10471,5]
[2]Current Patent Assignee: TOHOKU UNIVERSITY - US2015/353489, 2015, A1
[3]Meng, Qingqing; Wang, Zengtao; Cui, Jiahua; Cui, Qing; Dong, Jinyun; Zhang, Qijing; Li, Shaoshun [Journal of Medicinal Chemistry, 2018, vol. 61, # 23, p. 10901 - 10909]
[4]Current Patent Assignee: SHANGHAI JIAO TONG UNIVERSITY - CN110396403, 2020, B

8
[ 288-32-4 ]
[ 139115-91-6 ]
[ 629626-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; triphenylphosphine	2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane 2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-iodoethane Triphenylphosphine (2.87 g, 10.94 mmol) and imidazole (0.75 g, 11.02 mmol) were dissolved in dichloromethane (15 ml), and the solution was stirred for 5 minutes. Then, iodine (2.78 g, 10.95 mmol) was added thereto, and the mixture was stirred for 10 minutes. A dichloromethane (4 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-ethanol (1.5 g, 7.308 mmol) was added dropwise thereto, and the mixture was stirred at room temperature for 1.5 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was filtered through celite, and a 5% aqueous sodium thiosulfate solution was added to the filtrate to remove iodine. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=85:15) to obtain 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (2.19 g, yield: 95%).

Reference： [1]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1

9
[ 34619-03-9 ]
[ 629626-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: methanol / 2 h / 20 °C / Inert atmosphere 2: triphenylphosphine; 1H-imidazole; iodine / dichloromethane / 1.5 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 2: triphenylphosphine; iodine
	Multi-step reaction with 2 steps 1: methanol / 2 h / 20 °C / Inert atmosphere 2: triphenylphosphine; 1H-imidazole; iodine / dichloromethane / 1.5 h / 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2019/224165, 2019, A1
[2]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1
[3]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1

10
[ 629626-40-0 ]
[ 174319-54-1 ]
α-[2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: 1-methoxycarbonyl-3-indoleacetic acid methyl ester With N,N,N,N,N,N-hexamethylphosphoric triamide; lithium dipropan-2-ylazanide In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane In tetrahydrofuran; cyclohexane at -78℃; for 1h;	1 α-[2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester α-[2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester In a nitrogen atmosphere, 1-methoxycarbonyl-3-indoleacetic acid methyl ester (500 mg, 2.022 mmol) and hexamethylphosphoric triamide (HMPA, 1.81 g, 10.11 mmol) were dissolved in tetrahydrofuran (4 ml), and the solution was cooled to -78° C. A 1.5 M solution of lithium diisopropylamide (LDA) in cyclohexane (2.02 ml, 1.5 eq) was slowly added dropwise thereto, and the mixture was stirred at -78° C. for 0.5 hours. To this reaction solution, a tetrahydrofuran (2 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (637 mg, 2.022 mmol) was slowly added dropwise, and the mixture was stirred at -78° C. for 1 hour. After the reaction was confirmed by TLC to be complete, the temperature was adjusted to 0° C., and the reaction was quenched by the addition of water (15 ml), followed by extraction with ethyl acetate (15 ml) three times. The organic layer was washed twice with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:2) to obtain α-[2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester (645 mg, yield: 79%): 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J=7.0 Hz, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.57 (s, 1H), 7.34 (t, J=7.7 Hz, 1H), 7.26 (t, J=7.3 Hz, 1H), 4.98 (s, 1H), 4.02-4.06 (m, 4H), 3.69 (s, 3H), 3.43-3.51 (m, 4H), 3.30 (m, 2H), 2.29 (m, 2H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 173.8, 155.9, 151.2, 135.4, 124.8, 123.1, 122.9, 119.2, 118.8, 115.2, 79.1, 69.8, 68.3, 52.7, 52.1, 40.3, 39.3, 32.2, 28.3; FAB-MS: m/z [M+H]+ 435.
79%	Stage #1: 1-methoxycarbonyl-3-indoleacetic acid methyl ester With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane In tetrahydrofuran; cyclohexane at -78℃; for 1h;	1 α-[2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester In a nitrogen atmosphere, 1-methoxycarbonyl-3-indoleacetic acid methyl ester (500 mg, 2.022 mmol) and hexamethylphosphoric triamide (HMPA, 1.81 g, 10.11 mmol) were dissolved in tetrahydrofuran (4 ml), and the solution was cooled to -78° C. A 1.5 M solution of lithium diisopropylamide (LDA) in cyclohexane (2.02 ml, 1.5 eq) was slowly added dropwise thereto, and the mixture was stirred at -78° C. for 0.5 hours. To this reaction solution, a tetrahydrofuran (2 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (637 mg, 2.022 mmol) was slowly added dropwise, and the mixture was stirred at -78° C. for 1 hour. After the reaction was confirmed by TLC to be complete, the temperature was adjusted to 0° C., and the reaction was terminated by the addition of water (15 ml), followed by extraction with ethyl acetate (15 ml) three times. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=8:2) to obtain α-[2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester (645 mg, yield: 79%): 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J=7.0 Hz, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.57 (s, 1H), 7.34 (t, J=7.7 Hz, 1H), 7.26 (t, J=7.3 Hz, 1H), 4.98 (s, 1H), 4.02-4.06 (m, 4H), 3.69 (s, 3H), 3.43-3.51 (m, 4H), 3.30 (m, 2H), 2.29 (m, 2H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 173.8, 155.9, 151.2, 135.4, 124.8, 123.1, 122.9, 119.2, 118.8, 115.2, 79.1, 69.8, 68.3, 52.7, 52.1, 40.3, 39.3, 32.2, 28.3; FAB-MS: m/z 435 [M+H]+.
79%	Stage #1: 1-methoxycarbonyl-3-indoleacetic acid methyl ester With N,N,N,N,N,N-hexamethylphosphoric triamide; lithium dipropan-2-ylazanide In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane In tetrahydrofuran; cyclohexane at -78℃; for 1h; Inert atmosphere;	1 α-[2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic Acid Methyl Ester In a nitrogen atmosphere, 1-methoxycarbonyl-3-indoleacetic acid methyl ester (500 mg, 2.022 mmol) and hexamethylphosphoric triamide (HMPA, 1.81 g, 10.11 mmol) were dissolved in tetrahydrofuran (4 ml), and the solution was cooled to -78° C. A 1.5 M solution of lithium diisopropylamide (LDA) in cyclohexane (2.02 ml, 1.5 eq) was slowly added dropwise thereto, and the mixture was stirred at -78° C. for 0.5 hours. To this reaction solution, a tetrahydrofuran (2 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (637 mg, 2.022 mmol) was slowly added dropwise, and the mixture was stirred at -78° C. for 1 hour. After the reaction was confirmed by TLC to be complete, the temperature was adjusted to 0° C., and the reaction was terminated by the addition of water (15 ml), followed by extraction with ethyl acetate (15 ml) three times. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=8:2) to obtain α-[2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester (645 mg, yield: 79%): 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J=7.0 Hz, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.57 (s, 1H), 7.34 (t, J=7.7 Hz, 1H), 7.26 (t, J=7.3 Hz, 1H), 4.98 (s, 1H), 4.02-4.06 (m, 4H), 3.69 (s, 3H), 3.43-3.51 (m, 4H), 3.30 (m, 2H), 2.29 (m, 2H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 173.8, 155.9, 151.2, 135.4, 124.8, 123.1, 122.9, 119.2, 118.8, 115.2, 79.1, 69.8, 68.3, 52.7, 52.1, 40.3, 39.3, 32.2, 28.3; FAB-MS: m/z 435 [M+H]+.

79%

Stage #1: 1-methoxycarbonyl-3-indoleacetic acid methyl ester With N,N,N,N,N,N-hexamethylphosphoric triamide; lithium dipropan-2-ylazanide In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane In tetrahydrofuran; cyclohexane at -78℃; for 1h; Inert atmosphere;

1 α-[2-(N-tert-Butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic Acid Methyl Ester In a nitrogen atmosphere, 1-methoxycarbonyl-3-indoleacetic acid methyl ester (500 mg, 2.022 mmol) and hexamethylphosphoric triamide (HMPA, 1.81 g, 10.11 mmol) were dissolved in tetrahydrofuran (4 ml), and the solution was cooled to -78° C. A 1.5 M solution of lithium diisopropylamide (LDA) in cyclohexane (2.02 ml, 1.5 eq) was slowly added dropwise thereto, and the mixture was stirred at -78° C. for 0.5 hours. To this reaction solution, a tetrahydrofuran (2 ml) solution of 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane (637 mg, 2.022 mmol) was slowly added dropwise, and the mixture was stirred at -78° C. for 1 hour. After the reaction was confirmed by TLC to be complete, the temperature was adjusted to 0° C., and the reaction was terminated by the addition of water (15 ml), followed by extraction with ethyl acetate (15 ml) three times. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=8:2) to obtain α-[2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-ethyl]-1-methoxycarbonyl-3-indoleacetic acid methyl ester (645 mg, yield: 79%): 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J=7.0 Hz, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.57 (s, 1H), 7.34 (t, J=7.7 Hz, 1H), 7.26 (t, J=7.3 Hz, 1H), 4.98 (s, 1H), 4.02-4.06 (m, 4H), 3.69 (s, 3H), 3.43-3.51 (m, 4H), 3.30 (m, 2H), 2.29 (m, 2H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 173.8, 155.9, 151.2, 135.4, 124.8, 123.1, 122.9, 119.2, 118.8, 115.2, 79.1, 69.8, 68.3, 52.7, 52.1, 40.3, 39.3, 32.2, 28.3; FAB-MS: m/z 435 [M+H]+.

Reference： [1]Current Patent Assignee: TOHOKU UNIVERSITY - US2015/353489, 2015, A1 Location in patent: Paragraph 0098; 0177; 0178
[2]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2019/224165, 2019, A1 Location in patent: Paragraph 0093; 0155-0156
[3]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1 Location in patent: Paragraph 0084-0085; 0148-0149
[4]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1 Location in patent: Paragraph 0084-0085; 0148-0149

11
[ 629626-40-0 ]
[ 174319-54-1 ]
α-[2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-ethyl]-3-indoleacetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: N,N,N,N,N,N-hexamethylphosphoric triamide; lithium diisopropyl amide / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C 2.1: sodium hydroxide; water / methanol / 2 h / 70 °C
	Multi-step reaction with 2 steps 1.1: N,N,N,N,N,N-hexamethylphosphoric triamide / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C 2.1: sodium hydroxide; water / methanol / 2 h / 70 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: TOHOKU UNIVERSITY - US2015/353489, 2015, A1
[2]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2019/224165, 2019, A1

12
[ 629626-40-0 ]
tert-butyl (R)-7-(3-fluoro-4-(methoxycarbonyl)phenoxy)-6-hydroxy-1-methyl-1-(2-oxo-2-(thiazol-2-ylamino)ethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
tert-butyl (R)-6-(2-(2-((tert-butoxycarbonyl)amino)ethoxy)ethoxy)-7-(3-fluoro-4-(methoxycarbonyl)phenoxy)-1-methyl-1-(2-oxo-2-(thiazol-2-ylamino)ethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 18-crown-6 ether; potassium carbonate In acetone at 65℃; for 18h;	57.C Step C: tert-butyl (R)-6-(2-(2-((tert-butoxycarbonyl)amino)ethoxy)ethoxy)-7-(3-fluoro-4- (methoxycarbonyl)phenoxy)-1-methyl-1-(2-oxo-2-(thiazol-2-ylamino)ethyl)-3,4- dihydroisoquinoline-2(1H)-carboxylate To a solution of Intermediate IVa, scheme 1, step L (85.0 mg, 0.149 mmol), the title compound from scheme 7, step B (46.9 mg, 0.149 mmol) and 18 crown 6 (98.0 mg, 0.372 mmol) in acetone (372 μL) was added potassium carbonate (25.7 mg, 0.186 mmol). The solution was heated to 65 °C for 18 hours overnight. It was then cooled to room temperature and concentrated. The crude material was purified by column chromatography on silica gel, eluting with 10-100 % ethyl acetate in hexanes to afford the title compound: LCMS m/z 759.7 [M + H]+.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2018/57409, 2018, A1 Location in patent: Page/Page column 87

13
[ 192132-77-7 ]
[ 629626-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium iodide In acetone at 65℃;	57.B Step B: tert-butyl (2-(2-iodoethoxy)ethyl)carbamate o a solution of the title compound from scheme 7, step A (525 mg, 1.461 mmol) in acetone (3.00 mL) was added sodium iodide (547 mg, 3.65 mmol). The reaction was heated to 65 °C. The reaction was cooled to room temperature, filtered and then concentrated under reduced pressure. It was taken up in ethyl acetate then washed with 1% aqueous sodium thiosulfate and brine. The organics were dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography on silican gel, eluting with 0-60% ethyl acetate in hexanes to afford the title compound: LCMS m/z 315.8 [M + H]+

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2018/57409, 2018, A1 Location in patent: Page/Page column 86

14
[ 629626-40-0 ]
3-hydroxy-3′-fluoro-6,7,10-trimethoxy-α-naphthoflavone [ No CAS ]
tert-butyl 2-(2- (3′-fluoro-6,7,10-trimethoxy-α-naphthoflavonol)ethoxy)ethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere;
95%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	1.3 Step 3 Under the protection of nitrogen, the 6,7,10-trimethoxy-3'-fluoro-α-naphthoflavone alcohol(0.2mmol, see the authorized patent CN 201410228733.0 for the synthesis method)And III-1 (0.4mmol) were dissolved in 10mL of dry N,N-dimethylformamide.Under thorough stirring, solid potassium carbonate (2 mmol) was added to the reaction solution in batches.The reaction was stirred overnight at room temperature, quenched with saturated ammonium chloride solution, and the organic phase was separated.After the aqueous phase was extracted with ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate.The crude product obtained by concentrating the organic phase under reduced pressure, After column chromatography, the yellow oily amino group is protected by tert-butoxy group 3'-fluoro-6,7,10-trimethoxy-α-naphthoflavone alcohol hydroxy-2-(2-aminoethoxy) ethyl ether derivative IV-1 (n=1),Yield: 95%.

Reference： [1]Meng, Qingqing; Wang, Zengtao; Cui, Jiahua; Cui, Qing; Dong, Jinyun; Zhang, Qijing; Li, Shaoshun [Journal of Medicinal Chemistry, 2018, vol. 61, # 23, p. 10901 - 10909]
[2]Current Patent Assignee: SHANGHAI JIAO TONG UNIVERSITY - CN110396403, 2020, B Location in patent: Paragraph 0036; 0040

15
[ 629626-40-0 ]
[ 4229-44-1 ]
[ 76-05-1 ]
tert-butyl (2-(2-(hydroxy(methyl)amino)ethoxy)ethyl)carbamate trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane; N-methylhydroxyamine hydrochloride With triethylamine In dimethyl sulfoxide at 70℃; for 1.5h; Inert atmosphere; Stage #2: trifluoroacetic acid Inert atmosphere;
62%	Stage #1: 2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-iodoethane; N-methylhydroxyamine hydrochloride With triethylamine In dimethyl sulfoxide at 70℃; for 1.5h; Inert atmosphere; Stage #2: trifluoroacetic acid In water; acetonitrile

Reference： [1]Kang, Dahye; Kim, Justin [Journal of the American Chemical Society, 2021, vol. 143, # 15, p. 5616 - 5621]
[2]Cheung, Sheldon T.; Kang, Dahye; Kim, Justin [Angewandte Chemie - International Edition, 2021, vol. 60, # 31, p. 16947 - 16952][Angew. Chem., 2021, vol. 133, # 31, p. 17084 - 17089]

16
[ 629626-40-0 ]
tert-butyl (2-(2-(piperazin-1-yl)ethoxy)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate; sodium iodide / acetone / 16 h / 70 °C 2: acetic acid; 10 wt% Pd(OH)2 on carbon; hydrogen / methanol / 4 h / 20 °C

Reference： [1]Current Patent Assignee: NEOPHORE - WO2021/148786, 2021, A1

17
[ 629626-40-0 ]
benzyl 5-((4-(2-(2-((tert-butoxycarbonyl)amino)ethoxy)ethyl)piperazin-1-yl)methyl)isoindoline-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium carbonate; sodium iodide / acetone / 16 h / 70 °C 2.1: acetic acid; 10 wt% Pd(OH)2 on carbon; hydrogen / methanol / 4 h / 20 °C 3.1: acetic acid / dichloromethane / 5 h / 20 °C 3.2: 24 h / 20 °C

Reference： [1]Current Patent Assignee: NEOPHORE - WO2021/148786, 2021, A1

18
[ 629626-40-0 ]
tert-butyl (2-(2-(4-(isoindolin-5-ylmethyl)piperazin-1-yl)ethoxy)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium carbonate; sodium iodide / acetone / 16 h / 70 °C 2.1: acetic acid; 10 wt% Pd(OH)2 on carbon; hydrogen / methanol / 4 h / 20 °C 3.1: acetic acid / dichloromethane / 5 h / 20 °C 3.2: 24 h / 20 °C 4.1: palladium 10% on activated carbon; hydrogen / ethanol / 12 h / 20 °C

Reference： [1]Current Patent Assignee: NEOPHORE - WO2021/148786, 2021, A1

19
[ 629626-40-0 ]
tert-butyl (2-(2-(4-((2-(2,4-dihydroxy-5-isopropylbenzoyl)isoindolin-5-yl)methyl)piperazin-1-yl)ethoxy)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium carbonate; sodium iodide / acetone / 16 h / 70 °C 2.1: acetic acid; 10 wt% Pd(OH)2 on carbon; hydrogen / methanol / 4 h / 20 °C 3.1: acetic acid / dichloromethane / 5 h / 20 °C 3.2: 24 h / 20 °C 4.1: palladium 10% on activated carbon; hydrogen / ethanol / 12 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 1 h / 120 °C / Microwave irradiation; Sealed tube

Reference： [1]Current Patent Assignee: NEOPHORE - WO2021/148786, 2021, A1

20
[ 629626-40-0 ]
[ 31166-44-6 ]
benzyl 4-(2-(2-((tert-butoxycarbonyl)amino)ethoxy)ethyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; sodium iodide In acetone at 70℃; for 16h;	Benzyl 4-(2-(2-((tert-butoxycarbonyl)amino)ethoxy)ethyl)piperazine-1-carboxylate (I) To a solution of tert- butyl (2-(2-iodoethoxy)ethyl)carbamate (H) (2.0 g, 6.35 mmol) and benzyl piperazine-1 -carboxylate (CAS No. 31166-44-6) (1.25 g, 5.72 mmol) in acetone (20 mL) were added K2CO3 (2.45g, 17.75mmole) and Nal (0.38 g, 2.54 mmol) at room temperature. The reaction mixture was heated at 70°C for 16 h. The reaction mixture was concentrated under vacuum, diluted with water (100 mL) and extracted with ethyl acetate (3 x 100 mL). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under vacuum; the crude material was purified by flash chromatography (silica gel, eluting with 2.5% (v/v) MeOH in DCM) yielding benzyl 4-(2-(2-((tert-butoxycarbonyl)amino) ethoxy)ethyl)piperazine-1-carboxylate (I) as a yellow oil (2.0 9, 77%). [00180] LCMS (Method A): 1.640 min, MS: ES+ 408.32 (M+1); 1H NMR (DMSO-d6, 400 MHz): d 1. 35 (s, 9H), 2.38 (t, J = 4.8Hz, 4H), 2.44 - 2.47 (m, 2H), 3.02 - 3.06 (m, 2H), 3.33 - 3.36 (m, 6H), 3. 48 (t, J = 5.6Hz, 2H), 5.06 (s, 2H), 6.80 (t, J = 5.2Hz, 1H), 7.29 - 7.39 (m, 5H).

Reference： [1]Current Patent Assignee: NEOPHORE - WO2021/148786, 2021, A1 Location in patent: Paragraph 00179-00180

21
[ 629626-40-0 ]
α-[2-(N-tert-butoxycarbonyl-2-aminoethoxy)-1-ethyl]-3-indoleacetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: N,N,N,N,N,N-hexamethylphosphoric triamide; lithium dipropan-2-ylazanide / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C / Inert atmosphere 2.1: sodium hydroxide; lithium hydroxide monohydrate / methanol / 2 h / 70 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: KAKE EDUCATIONAL INSTITUTION; TOHOKU UNIVERSITY - US2022/106270, 2022, A1

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
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Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	629626-40-0	MDL No. :	MFCD24467264
Formula :	C₉H₁₈INO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RGHXWCUQSIGAJS-UHFFFAOYSA-N
M.W :	315.15	Pubchem ID :	22247763
Synonyms :

Signal Word:	Danger	Class:	6.1
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Hazard Statements:	H301-H311-H331-H341	Packing Group:	Ⅲ
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P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
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.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 629626-40-0 ] {[proInfo.proName]}

Quality Control of [ 629626-40-0 ]

Related Doc. of [ 629626-40-0 ]

Product Details of [ 629626-40-0 ]

Safety of [ 629626-40-0 ]

Application In Synthesis of [ 629626-40-0 ]

[ 629626-40-0 ] Synthesis Path-Downstream 1~21

Related Functional Groups of
[ 629626-40-0 ]

Esters

Iodides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed

[ CAS No. 629626-40-0 ] {[proInfo.proName]}

Quality Control of [ 629626-40-0 ]

Related Doc. of [ 629626-40-0 ]

Product Details of [ 629626-40-0 ]

Safety of [ 629626-40-0 ]

Application In Synthesis of [ 629626-40-0 ]

[ 629626-40-0 ] Synthesis Path-Downstream 1~21

Related Functional Groups of [ 629626-40-0 ]

Esters

Iodides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 629626-40-0 ]