Name: 21663-79-6|O-(Prop-2-yn-1-yl)hydroxylamine hydrochloride|98%
Brand: Ambeed
SKU: A670545
Price: 42.0 USD
Availability: InStock
Rating: 99 (27 reviews)

1
[ 674-82-8 ]
[ 21663-79-6 ]
[ 133146-83-5 ]

Yield	Reaction Conditions	Operation in experiment
58%	With triethylamine In methanol; toluene at 0 - 5℃; for 0.5h;

Reference： [1]Inglesi; Nicola; Magnetti [Il Farmaco, 1990, vol. 45, # 12, p. 1327 - 1340]

2
[ 500-22-1 ]
[ 21663-79-6 ]
[ 22892-91-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride for 1h; Ambient temperature;

Reference： [1]Toja, E; Bonetti, C; Butti, A; Hunt, P; Fortin, M; et al. [European Journal of Medicinal Chemistry, 1992, vol. 27, # 5, p. 519 - 526]

3
[ 114485-48-2 ]
[ 21663-79-6 ]
[ 139886-21-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	In water for 1h; Ambient temperature;

Reference： [1]Toja; Bonetti; Butti; Hunt; Fortin; Barzaghi; Formento; Maggioni; Nencioni; Galliani [European Journal of Medicinal Chemistry, 1991, vol. 26, # 9, p. 853 - 868]

4
[ 114485-45-9 ]
[ 21663-79-6 ]
[ 139886-24-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	In water for 1h; Ambient temperature;

Reference： [1]Toja; Bonetti; Butti; Hunt; Fortin; Barzaghi; Formento; Maggioni; Nencioni; Galliani [European Journal of Medicinal Chemistry, 1991, vol. 26, # 9, p. 853 - 868]

5
[ 21663-79-6 ]
(1S,3S,4S)-1-Aza-bicyclo[2.2.1]heptane-3-carbaldehyde [ No CAS ]
(1S,3S,4S)-1-Aza-bicyclo[2.2.1]heptane-3-carbaldehyde O-prop-2-ynyl-oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol Ambient temperature;

Reference： [1]Bromidge, Steven M.; Brown, Frank; Cassidy, Frederick; Clark, Michael S. G.; Dabbs, Steven; Hadley, Michael S.; Hawkins, Julie; Loudon, Julia M.; Naylor, Christopher B.; Orlek, Barry S.; Riley, Graham J. [Journal of Medicinal Chemistry, 1997, vol. 40, # 26, p. 4265 - 4280]

6
[ 21663-79-6 ]
[ 142034-97-7 ]
E-(+/-)-1-azabicyclo[2.2.1]heptan-3-one, O-2-propynyloxime [ No CAS ]
Z-(+/-)-1-azabicyclo[2.2.1]heptan-3-one, O-2-propynyloxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol for 18h; Ambient temperature; Title compound not separated from byproducts;
	In methanol for 18h; Ambient temperature;

Reference： [1]Tecle, Halle; Barrett, Stephen D.; Lauffer, David J.; Augelli-Szafran, Corinne; Brann, Mark R.; Callahan, Michael J.; Caprathe, Bradley W.; Davis, Robert E.; Doyle, Patricia D.; Eubanks, David; Lipiniski, William; Mirzadegan, Tara; Moos, Walter H.; Moreland; Nelson, Carrie B.; Pavia, Michael R.; Raby, Charlotte; Schwarz, Roy D.; Spencer, Carolyn J.; Thomas, Anthony J.; Jaen, Juan C. [Journal of Medicinal Chemistry, 1998, vol. 41, # 14, p. 2524 - 2536]
[2]Tecle, Halle; Barrett, Stephen D.; Lauffer, David J.; Augelli-Szafran, Corinne; Brann, Mark R.; Callahan, Michael J.; Caprathe, Bradley W.; Davis, Robert E.; Doyle, Patricia D.; Eubanks, David; Lipiniski, William; Mirzadegan, Tara; Moos, Walter H.; Moreland; Nelson, Carrie B.; Pavia, Michael R.; Raby, Charlotte; Schwarz, Roy D.; Spencer, Carolyn J.; Thomas, Anthony J.; Jaen, Juan C. [Journal of Medicinal Chemistry, 1998, vol. 41, # 14, p. 2524 - 2536]

7
[ 1445-73-4 ]
[ 21663-79-6 ]
N-methylpiperidin-4-one O-prop-2-ynyloxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol for 18h; Ambient temperature;

Reference： [1]Xu, Rong; Sim, Meng-Kwoon; Go, Mei-Lin [Journal of Medicinal Chemistry, 1998, vol. 41, # 17, p. 3220 - 3231]

8
[ 532-24-1 ]
[ 21663-79-6 ]
8-Methyl-8-aza-bicyclo[3.2.1]octan-3-one O-prop-2-ynyl-oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol for 18h; Ambient temperature;

Reference： [1]Xu, Rong; Sim, Meng-Kwoon; Go, Mei-Lin [Journal of Medicinal Chemistry, 1998, vol. 41, # 17, p. 3220 - 3231]

9
[ 21663-79-6 ]
1,3-Diamino-propan-2-one; hydrochloride [ No CAS ]
1,3-Diamino-propan-2-one O-prop-2-ynyl-oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol for 48h; Heating;

Reference： [1]Plate, Ralf; Plaum, Marc J. M.; Pintar, Peter; Jans, Christian G.; Boer, Thijs de; et al. [Bioorganic and medicinal chemistry, 1998, vol. 6, # 9, p. 1403 - 1420]

10
[ 21663-79-6 ]
[ 136192-67-1 ]
2-(4,6-Dimethoxy-pyrimidin-2-yloxy)-6-{1-[(E)-prop-2-ynyloxyimino]-ethyl}-benzoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate In methanol for 6h; Heating;

Reference： [1]Tamaru; Masuyama; Sato; Takabe; Inoue; Hanai [Pesticide Science, 1997, vol. 49, # 1, p. 76 - 84]

11
[ 21663-79-6 ]
Carbonic acid (3R,4R,5R,6R)-6-(3-acetyl-4-hydroxy-8-methyl-2-oxo-2H-chromen-7-yloxy)-3-methoxy-2,2-dimethyl-5-(tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-4-yl ester 4-nitro-phenyl ester [ No CAS ]
C₂₉H₃₅NO₁₂ [ No CAS ]

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

Reference： [1]Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Haesslein, Jean-Luc; Klich, Michel; Dupuis-Hamelin, Claudine; Mauvais, Pascale; Lassaigne, Patrice; Bonnefoy, Alain; Musicki, Branislav [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 2, p. 161 - 165]

12
[ 21663-79-6 ]
4-Hydroxy-7-((3aR,4R,7R,7aR)-7-methoxy-6,6-dimethyl-2-oxo-tetrahydro-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-8-methyl-2,2-dioxo-1,2-dihydro-2λ⁶-isothiochromene-3-carboxylic acid ethyl ester [ No CAS ]
C₂₅H₃₁NO₁₂S [ No CAS ]
C₂₅H₃₁NO₁₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With lithium perchlorate In pyridine at 20℃;

Reference： [1]Peixoto, Christophe; Laurin, Patrick; Klich, Michel; Dupuis-Hamelin, Claudine; Mauvais, Pascale; Lassaigne, Patrice; Bonnefoy, Alain; Musicki, Branislav [Tetrahedron Letters, 2000, vol. 41, # 11, p. 1741 - 1745]

13
[ 21663-79-6 ]
4-hydroxy-7-(7-methoxy-6,6-dimethyl-2-oxo-tetrahydro-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-8-methyl-2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiine-3-carboxylic acid (3-chloro-phenyl)-amide [ No CAS ]
C₂₈H₂₉ClN₂O₁₂S [ No CAS ]
C₂₈H₂₉ClN₂O₁₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With lithium perchlorate In pyridine at 20℃;

Reference： [1]Peixoto, Christophe; Laurin, Patrick; Klich, Michel; Dupuis-Hamelin, Claudine; Mauvais, Pascale; Lassaigne, Patrice; Bonnefoy, Alain; Musicki, Branislav [Tetrahedron Letters, 2000, vol. 41, # 11, p. 1741 - 1745]

14
[ 21663-79-6 ]
[ 200727-44-2 ]
C₂₇H₃₀N₂O₁₁ [ No CAS ]
C₂₇H₃₀N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

15
[ 21663-79-6 ]
3-Acetyl-7-((3aR,4S,6S,7S,7aR)-6-ethyl-7-methoxy-2-oxo-tetrahydro-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-4-hydroxy-8-methyl-chromen-2-one [ No CAS ]
C₂₇H₃₀N₂O₁₁ [ No CAS ]
C₂₇H₃₀N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

16
[ 21663-79-6 ]
[ 229308-42-3 ]
C₂₈H₃₂N₂O₁₁ [ No CAS ]
C₂₈H₃₂N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

17
[ 21663-79-6 ]
3-Acetyl-4-hydroxy-7-((3aR,4R,6S,7R,7aR)-7-methoxy-6-methyl-2-oxo-6-vinyl-tetrahydro-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-8-methyl-chromen-2-one [ No CAS ]
C₂₈H₃₀N₂O₁₁ [ No CAS ]
C₂₈H₃₀N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

18
[ 21663-79-6 ]
3-Acetyl-7-((3aR,4R,7R,7aR)-6,6-diethyl-7-methoxy-2-oxo-tetrahydro-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-4-hydroxy-8-methyl-chromen-2-one [ No CAS ]
C₂₉H₃₄N₂O₁₁ [ No CAS ]
C₂₉H₃₄N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

19
[ 21663-79-6 ]
[ 297754-73-5 ]
C₂₉H₃₂N₂O₁₁ [ No CAS ]
C₂₉H₃₂N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

20
[ 21663-79-6 ]
3-Acetyl-7-((3aR,4R,6S,7R,7aR)-6-allyl-7-methoxy-6-methyl-2-oxo-tetrahydro-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-4-hydroxy-8-methyl-chromen-2-one [ No CAS ]
C₂₉H₃₂N₂O₁₁ [ No CAS ]
C₂₉H₃₂N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

21
[ 21663-79-6 ]
C₂₄H₂₆O₁₀ [ No CAS ]
C₃₀H₃₄N₂O₁₁ [ No CAS ]
C₃₀H₃₄N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; lithium perchlorate at 20℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Benedetti, Yannick; Lachaud, Sylvette; Chatreaux, Fabienne; Haesslein, Jean-Luc; Iltis, Alain; Pierre, Christine; Khider, Jean; Tessot, Nicole; Airault, Marlene; Demassey, Jacques; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain; Vicat, Pascale; Klich, Michel [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1695 - 1699]

22
[ 102241-63-4 ]
[ 21663-79-6 ]
C₂₄H₁₉N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In methanol; dichloromethane at 20℃;

Reference： [1]Plate, Ralf; Jans, Christan G.J.M; Plaum, Marc J.M; De Boer, Thijs [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 4, p. 1143 - 1152]

23
[ 21663-79-6 ]
[ 158142-48-4 ]
(Z)-1,4,5,6-tetrahydro-4-pyrimidinecarboxaldehyde O-(2-propynyl)-oxime monohydrochloride [ No CAS ]
1,4,5,6-tetrahydro-pyrimidine-4-carbaldehyde O-prop-2-ynyl-oxime; hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: O-(prop-2-yn-1-yl)hydroxylamine hydrochloride; 1,4,5,6-tetrahydro-4-pyrimidinecarboxaldehyde In methanol at 20℃; Stage #2: In ethanol Heating; Title compound not separated from byproducts;

Reference： [1]Plate, Ralf; Jans, Christan G.J.M; Plaum, Marc J.M; De Boer, Thijs [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 4, p. 1143 - 1152]

24
[ 21663-79-6 ]
[ 7693-46-1 ]
4-Hydroxy-7-[(1R,2R,3R)-3-hydroxy-5,5-dimethyl-2-(tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-8-methyl-2-oxo-2H-chromene-3-carboxylic acid ethyl ester [ No CAS ]
C₃₀H₃₇NO₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-Nitrophenyl chloroformate; 4-Hydroxy-7-[(1R,2R,3R)-3-hydroxy-5,5-dimethyl-2-(tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-8-methyl-2-oxo-2H-chromene-3-carboxylic acid ethyl ester With dmap In dichloromethane at 0℃; Stage #2: O-(prop-2-yn-1-yl)hydroxylamine hydrochloride With dmap; sodium hydride In N,N-dimethyl-formamide at 0℃;

Reference： [1]Musicki, Branislav; Periers, Anne-Marie; Piombo, Laurent; Laurin, Patrick; Klich, Michel; Dupuis-Hamelin, Claudine; Lassaigne, Patrice; Bonnefoy, Alain [Tetrahedron Letters, 2003, vol. 44, # 52, p. 9259 - 9262]

25
N'-(benzyloxy)-N,N-dimethylformamidine [ No CAS ]
[ 21663-79-6 ]
C₁₁H₁₂N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	In methanol Heating;

Reference： [1]Díaz, David D.; Lewis, Warren G.; Finn [Synlett, 2005, # 14, p. 2214 - 2218]

26
[ 769171-41-7 ]
[ 21663-79-6 ]
C₂₅H₂₃Cl₂N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 20℃; for 10h;	39 Production Example 39; 160 mg of the present compound (38) was dissolved in 2 ml of pyridine, 50 mg of 2-propynyloxyamine hydrochloric acid salt was added to the mixture at room temperature, and the mixture was stirred at room temperature for ten hours. The reaction mixture was concentrated under reduced pressure. Dilute hydrochloric acid were added to the residue, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 170 mg of the compound of formula (39):

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - EP1607390, 2005, A1 Location in patent: Page/Page column 60

27
C₂₁H₁₇Cl₃N₂O₄ [ No CAS ]
[ 21663-79-6 ]
C₂₄H₂₀Cl₃N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 0 - 20℃; for 5h;	35 Production Example 35; 150 mg of the present compound (34) was dissolved in 2 ml of pyridine, 40 mg of 2-propynyloxyamine hydrochloric acid salt was added to the mixture under ice-cooling, and the mixture was stirred at room temperature for five hours. The reaction mixture was concentrated under reduced pressure. Dilute hydrochloric acid were added to the residue, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 150 mg of the compound of formula (35): [] (hereinafter, referred as the present compound (35)).

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - EP1607390, 2005, A1 Location in patent: Page/Page column 59

Yield	Reaction Conditions	Operation in experiment
		58 (10Z)-8-(2-Dimethylaminoethoxy)-2,3-methylenedioxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime hydrochloride EXAMPLE 58 (10Z)-8-(2-Dimethylaminoethoxy)-2,3-methylenedioxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime hydrochloride The expected product is obtained in accordance with the procedure described in Example 1, starting from 5,6-methylenedioxyphthalide, the compound described in Preparation A and O-(2-propynyl)hydroxylamine hydrochloride. Melting point: >260° C.

Yield	Reaction Conditions	Operation in experiment
		59 (10E)-8-(2-Dimethylaminoethoxy)-1,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime hydrochloride EXAMPLE 59 (10E)-8-(2-Dimethylaminoethoxy)-1,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime hydrochloride The expected product is obtained in accordance with the procedure described in Example 1, starting from 4,6-dimethoxyphthalide, the compound described in Preparation A and O-(2-propynyl)hydroxylamine hydrochloride. Melting point: 254° C.

30
[ 64019-78-9 ]
[ 42454-06-8 ]
[ 21663-79-6 ]
[ 478287-00-2 ]

Yield	Reaction Conditions	Operation in experiment
		65 (10E)-1,4-Dimethoxy-8-hydroxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime EXAMPLE 65 (10E)-1,4-Dimethoxy-8-hydroxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime The expected product is obtained in accordance with the procedure described in Steps A to F of Example 1, starting from 4,7-dimethoxyphthalide, 5-hydroxy-2-nitrobenzaldehyde and O-(2-propynyl)hydroxylamine hydrochloride.

Reference： [1]Current Patent Assignee: SERVIER MONDE - US2003/125369, 2003, A1

31
[ 3465-69-8 ]
[ 42454-06-8 ]
[ 21663-79-6 ]
[ 478286-97-4 ]

Yield	Reaction Conditions	Operation in experiment
		64 (10Z)-2,4Dimethoxy-8-hydroxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime EXAMPLE 64 (10Z)-2,4Dimethoxy-8-hydroxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime The expected product is obtained in accordance with the procedure described in Steps A to F of Example 1, starting from 5,7-dimethoxyphthalide, 5-hydroxy-2-nitrobenzaldehyde and O-(2-propynyl)hydroxylamine hydrochloride. Melting point: 175° C.

Reference： [1]Current Patent Assignee: SERVIER MONDE - US2003/125369, 2003, A1

32
[ 114485-48-2 ]
[ 21663-79-6 ]
[ 114485-72-2 ]

Yield	Reaction Conditions	Operation in experiment
		21 1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-propargyloxime hydrochloride EXAMPLE 21 1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-propargyloxime hydrochloride The operation is done as in example 12, starting with 1.47 g of 1,2,5,6-tetrahydropyridin-3-carboxaldehyde hydrochloride (Chem.Ber. 40, 4685 (1907) and 1.07 g of O-propargylhydroxylaminehydrochloride (U.S. Pat. No. 3,398,180). 1.2 g of the expected product is obtained. m.p. 202° C.

Reference： [1]Current Patent Assignee: SANOFI - US5219872, 1993, A

33
[ 114485-45-9 ]
[ 21663-79-6 ]
1-methyl-1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-propargyloxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water	12 1-methyl-1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-propargyloxime (in the form of the hydrochloride) STR23 EXAMPLE 12 1-methyl-1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-propargyloxime (in the form of the hydrochloride) STR23 1.23 g (0.00114 mol) of O-propargylhydroxylamine hydrochloride is added to a solution of 1.84 g (0.0114 mol) of 1-methyl-1,2,5,6-tetrahydropyridin-3-carboxaldehyde hydrochloride in 15 cm3 of water, with agitation for 1 hour at ambient temperature. The reactional mixture is evaporated to dryness and the residue is crystallized from absolute ethanol. Yield 2.2 g (about 90%). White crystalline powder with m.p. 157° C. (decomposes).

Reference： [1]Current Patent Assignee: SANOFI - US5219872, 1993, A

34
[ 45675-76-1 ]
[ 21663-79-6 ]
[ 149350-06-1 ]

Yield	Reaction Conditions	Operation in experiment
1.05 g (61%)	In methanol	2 Z-(+-)-1-Azabicyclo[3.2.1]octan-6-one, O-(2-propynyl)oxime hydrochloride EXAMPLE 2 Z-(+-)-1-Azabicyclo[3.2.1]octan-6-one, O-(2-propynyl)oxime hydrochloride 1-Azabicyclo[3.2.1]octan-6-one (1.0 g, 8 mmol) and O-(2-propynyl)hydroxylamine hydrochloride (0.86 g, 8 mmol) were dissolved in 25 mL of methanol and stirred at room temperature for 3 days. The reaction mixture was concentrated in vacuo to afford a crystalline solid that was recrystallized from ethanol/ether to give 1.05 g (61%) of the title product, m.p. 169°-171° C.

Reference： [1]Current Patent Assignee: PFIZER INC - US5318978, 1994, A

35
[ 61798-04-7 ]
[ 21663-79-6 ]
1,6-Dihydro-5(4H)-pyrimidinone O-(2-propynyl)oxime monohydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
410 mg (36%)	In methanol	3 1,6-Dihydro-5(4H)-pyrimidinone O-(2-propynyl)oxime monohydrochloride EXAMPLE 3 1,6-Dihydro-5(4H)-pyrimidinone O-(2-propynyl)oxime monohydrochloride 1,3-diaminoacetone dihydrochloride monohydrate (1.10 g, 6.14 mmol) was dissolved in refluxing methanol and O-(2-propynyl)hydroxylamine hydrochloride (0.730 g, 6.75 mmol) was added. After refluxing for 48 hours the solvent was evaporated. The crude product was dissolved in methanol and an excess of trimethylorthoformate was added to the reaction mixture and heated to reflux. After 24 hours the solvent was removed in vacuo. Crystallization from methanol/ethyl acetate afforded 410 mg (36%) of light-brown material. Mp. 205.0° C.

Reference： [1]Current Patent Assignee: ORGANON & CO - US5470856, 1995, A

36
[ 21663-79-6 ]
[ 71470-45-6 ]
2-methylthiomethoxyimino-2-(4-formamidopyrimidin-2-yl)acetic acid [ No CAS ]
2-propargyloxyimino-2-(4-formamidopyrimidin-2-yl)acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		7 PREPARATION 7 PREPARATION 7 2-Propargyloxyimino-2-(4-formamidopyrimidin-2-yl)acetic acid (syn isomer) was obtained from S-methyl (4-formamidopyrimidin-2-yl)thioglyoxylate and O-propargylhydroxylamine hydrochloride by treating them according to a similar manner to that of Preparation 6. mp 78° to 83° C. (dec.). IR (Nujol): 3250, 1710, 1570, 1210, 1010 cm-1. NMR (DMSO-d6 +D2 O, δ): 3.63 (1H, t, J=2 Hz), 4.90 (2H, d, J=2 Hz), 7.3-7.7 (1H, m), 8.65 (1H, d, J=8 Hz), 8.7-9.1 (1H, m).

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - US4407798, 1983, A

Yield	Reaction Conditions	Operation in experiment
86%		P.3.2 (2) (2) Synthesis of propargyloxyamine hydrochloride 5.4 Grams (27 mmol) of N-(propargyloxy)phthalimide was dissolved in 30 ml of chloroform, and further, the resultant solution was dissolved in 30 ml of ethanol. To this was added 2.6 ml (54 mmol) of hydrazine hydrate, and the mixture was stirred at 70°C for 1 hour. The reaction mixture was diluted with 100 ml of chloroform, a formed solid was removed by filtration, and the filtrate was washed with 50 ml of water. The resultant organic layer was dried over anhydrous sodium sulfate and acidified with concentrated hydrochloric acid, and the solvent was distilled off. The resultant residue was dried under reduced pressure to give 2.5 g (yield 86 %) of propargyloxyamine hydrochloride in the form of a yellowish acicular crystal. NMR (ppm, solvent: deutero chloroform + deutero methanol, internal standard: tetramethylsilane): 2.95(1H,t, J = 2), 4.80(2H,d, J = 2)

38
[ 183238-10-0 ]
[ 21663-79-6 ]
4-propargyloxyimino-5-methylthiochroman-6-carboxylic acid-1,1-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine; hydrogenchloride In ethanol; water	1 (1) (1) Alkoxyimino-forming step 1.4 Grams (5.5 mmol) of 5-methylthiochroman-4-one-6-carboxylic acid-1,1-dioxide and 1.2 g (11 mmol) of propargyloxyamine hydrochloride were suspended in 15 ml of ethanol, 1.3 ml (16 mmol) of pyridine was added, and the mixture was refluxed for 9 hours. The reaction mixture was diluted with 30 ml of water, acidified by adding 5 % hydrochloric acid and extracted with 150 ml of ethyl acetate. The resultant organic layer was washed with 50 ml of water and dried over anhydrous sodium sulfate, and the solvent was distilled off. The resultant residue was dried under reduced pressure to give 1.7 g (yield 100 %) of 4-propargyloxyimino-5-methylthiochroman-6- carboxylic acid-1,1-dioxide in the form of a yellowish glass-like solid. NMR (ppm, solvent: deutero acetone, internal standard: tetramethylsilane): 2.71(3H,s), 3.07(1H,t, J = 2), 3.4-3.5(4H,m), 4.90(2H,d, J = 2), 7.85(1H,d, J = 7), 8.05(1H,d, J = 7)

Reference： [1]Current Patent Assignee: IDEMITSU KOSAN CO LTD - EP818455, 1998, A1

39
[ 5176-21-6 ]
[ 21663-79-6 ]
Z-1-Azabicyclo[2.2.2]octane-3-carboxaldehyde, O-propynyloxime, hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		8 E- and Z-1-Azabicyclo[2.2.2]octane-3-carboxaldehyde, O-propynyloxime, hydrochloride EXAMPLE 8 E- and Z-1-Azabicyclo[2.2.2]octane-3-carboxaldehyde, O-propynyloxime, hydrochloride This was prepared by reacting 1-azabicyclo[2.2.2]octane-3-carboxaldehyde (1.61 g, 11.6 mmol) and O-propargylhydroxylamine hydrochloride (1.25 g, 11.6 mmol) to afford the title product, 1.6 g (60%), mp 138°-141° C. C11 H17 ClN2 O Calc.: C, 57.76; H, 7.49; N, 12.25. Found: C, 57.58; H, 7 64; N, 12.28. Mass Spec: m/e 192 (M+ for free base). 1 H NMR: δ (CDCl3) 1.77-2.08 (4H, m); 2.20-2.41 (1H, m); 2.42-2.48 (1H, m); 2.93-3.02 (1H, m); 3.11-3.59 (5H, m); 3.66-3.75 (1H, m); 4.59-4.61 STR22 4.62-4.63 STR23 6.89-6.92 STR24 7.43-7.45 STR25 11.98 (1H, br. s). 13 C NMR: δ (CDCl3) 18.69, 19.43, 23.09, 23.24, 23.49, 23.66, 31.31, 34.61, 45.76, 45.95, 46.05, 47.07, 50.06, 61.62, 61.82, 74.80, 74.95, 76.35, 78.99, 149.20, 151.08.

Reference： [1]Current Patent Assignee: PFIZER INC - US4937239, 1990, A

40
[ 129964-37-0 ]
[ 21663-79-6 ]
O-propargyl oxime hydrochloride [ No CAS ]
1-Azabicyclo[2.2.2]oct-2-ene-3-carboxaldehyde, O-propynyl oxime, hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	In methanol	18 1-Azabicyclo[2.2.2]oct-2-ene-3-carboxaldehyde, O-propynyl oxime, hydrochloride EXAMPLE 18 1-Azabicyclo[2.2.2]oct-2-ene-3-carboxaldehyde, O-propynyl oxime, hydrochloride 1-Azabicyclo[2.2.2]oct-2-ene-3-carboxaldehyde (1 g, 7.29 mmol) was dissolved in 50 ml of methanol. O-propargyl hydroxylamine hydrochloride was added to the reaction, and the reaction was stirred at room temperature for 16 hours. The reaction was concentrated in vacuo to afford a gummy solid which was recrystallized from isopropanol-isopropyl ether to give the O-propargyl oxime hydrochloride (0.91 g, 55%), mp 175°-176° C., dec. C11 H15 ClN2 O Calc.: C, 58.28; H, 6.67; N, 12.36. Found: C, 58.13; H, 6.65; N, 12.37. Mass Spec: m/e 190.1 (M+ for free base). 1 H NMR: δ (CDCl3) 1.77 (2H, m); 2.02 (2H, m); 2.50 (1H, m); 3.13 (2H, m); 3.59 (2H, m); 3.72 (1H, m); 4.72 (2H, d); 6.96 (1H, d); 7.79 (1H, s); 14.0 (1H, br. s). 13 C NMR: δ (CDCl3) 23.09, 24.69, 50.11, 62.39, 75.29, 77.91, 130.37, 141.69, 143.25.

Reference： [1]Current Patent Assignee: PFIZER INC - US4937239, 1990, A

41
[ 925440-61-5 ]
[ 21663-79-6 ]
[ 925440-92-2 ]

Yield	Reaction Conditions	Operation in experiment
49%	With sodium hydrogencarbonate In tetrahydrofuran; methanol at 20℃; for 4h;	158 (9aS)-8-Acetyl-1,7-dihydroxy-N-(4-hydroxy-2,3,6-trimethylbenzyl)-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide produced in Example (132b) (252 mg, 0.51 mmol) was dissolved in tetrahydrofuran:methanol (2:1, 5 mL). O-Propargylhydroxylamine hydrochloride (82 mg, 0.77 mmol) and sodium bicarbonate (64 mg, 0.77 mmol) were added at room temperature, and the mixture was stirred for four hours. The reaction solution was treated in the same manner as in Example 87 to give the title target compound (136 mg, 49%) as a yellow solid. 1H-NMR (CDCl3 400MHz):δ ppm: 1.70 (3H, s), 2.16 (3H, s), 2.29 (3H, s), 2.32 (3H, s), 2.49 (3H, s), 2.61 (1H, m), 3.77 (3H, s), 4.53-4.63 (2H, m), 4.67 (2H, d, J=2.4Hz), 5.78 (1H, s), 5,80 (1H, s), 6.23 (1H, s), 6.56 (1H, s), 6.70 (1H, m), 11.06 (1H, s), 15.36 (1H, brs) MS (ESI) m/z: 547 (M+H)+

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1914229, 2008, A1 Location in patent: Page/Page column 149

42
[ 880473-81-4 ]
[ 21663-79-6 ]
[ 880473-00-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate In ethanol

Reference： [1]Ali, Abdelselam; Altamore, Timothy M.; Bliese, Marianne; Fisara, Petr; Liepa, Andris J.; Meyer, Adam G.; Nguyen, Oahn; Sargent, Roger M.; Sawutz, David G.; Winkler, David A.; Winzenberg, Kevin N.; Ziebell, Angela [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 1, p. 252 - 255]

43
[ 880473-75-6 ]
[ 21663-79-6 ]
[ 880472-94-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate In ethanol

Reference： [1]Ali, Abdelselam; Altamore, Timothy M.; Bliese, Marianne; Fisara, Petr; Liepa, Andris J.; Meyer, Adam G.; Nguyen, Oahn; Sargent, Roger M.; Sawutz, David G.; Winkler, David A.; Winzenberg, Kevin N.; Ziebell, Angela [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 1, p. 252 - 255]

44
[ 4616-63-1 ]
[ 21663-79-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 2-(prop-2-yn-1-yloxy)isoindoline-1,3-dione With methylhydrazine In dichloromethane at 0 - 20℃; for 2h; Stage #2: With hydrogenchloride In 1,4-dioxane at 0℃;	1-2 Preparation of SAC-1010 After 500 mg of hydroxyphthalimide (Aldrich) was dissolved in 5 ml of dimethylformamide under argon flow, 501 mg of propargyl bromide (Aldrich) was added, and 0.5 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene (Aldrich) was slowly added. After the mixture was stirred at 60° C. for 2 hours, the temperature was again lowered to room temperature, and then the reaction was stopped by adding a 2 N hydrochloric acid solution. The reaction liquid was diluted by adding 20 ml of ethyl acetate, followed by drying over magnesium sulfate and then filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixed eluent of ethyl acetate/hexane (1:5) and then dried to obtain 396 mg of a white solid (yield: 64%). The white solid was dissolved in 5 ml of dichloromethane, and 0.17 ml of methyl hydrazine (TCI) was slowly added at 0° C. After the reaction liquid was stirred at room temperature for 2 hours, the temperature was again lowered to 0° C. The generated solid was then filtered out, and 1 ml of a 4 M-hydrochloric acid dioxane solution (Aldrich) was added to the residual filtrate, followed by filtration and drying, to obtain 230 mg of a solid (yield: 100%). 13 mg of the obtained solid and 55 mg of SAC-0906 obtained as obtained above were dissolved in 1 ml of pyridine (Aldrich) under argon flow, followed by stirring at 80° C. for 2 hours. After the temperature was lowered to room temperature, the reaction liquid was acidified by adding a 2 N hydrochloric acid solution, followed by extraction with 20 ml of diethyl ether, drying over magnesium sulfate, and filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixed eluent of ethyl acetate/hexane (1:5) to obtain the target compound SAC-1010 (53 mg, yield: 88%). 1H-NMR (300 MHz, CDCl3) δ5.92-5.76 (m, 2H), 5.34-5.33 (m, 1H), 5.28-5.25 (m, 1H), 5.15 (m, 1H), 4.61 (d, J=2.4 Hz, 2H), 4.25-4.05 (m, 3H), 3.68-3.41 (m, 1H), 2.42-0.62 (m, 36H)
78%	Stage #1: 2-(prop-2-yn-1-yloxy)isoindoline-1,3-dione With hydrazine hydrate In diethyl ether at 20℃; for 0.75h; Stage #2: With hydrogenchloride In diethyl ether
73%	Stage #1: 2-(prop-2-yn-1-yloxy)isoindoline-1,3-dione With hydrazine hydrate In diethyl ether at 20℃; for 0.5h; Stage #2: With hydrogenchloride In 1,4-dioxane	O-propargyl-hydroxylamine hydrochloride (S4): According to published procedure,[2] phthalimide-protected O-(prop-2-ynyl)hydroxylamine (200 mg, 1.09 mmol) was stirred with hydrazine monohydrate (55 μL, 1.09 mmol, 1.1 equiv.) for a few minutes in an oven dried round-bottom flask with magnetic stir bar before the addition of diethyl ether (1 mL, 0.1M). The reaction was stirred vigorously at room temperature for 30 min. The sticky white precipitate was filtered off and rinsed with ether (4 mL). Ethereal HCl (200 μL of a 4M solution in dioxane) was added to the filtrate with continuous stirring. The yellow-white precipitate was filtered and dried under vacuum overnight to give O-propargyl-hydroxylamine hydrochloride (S4) as a white solid (77.3 mg, 0.719 mmol, 73% yield). Literature: 78% yield. Additional analytical data for S4: 1H NMR (400 MHz, CD3OD) δ 3.38 (dd, J = 2.4, 2.4 Hz, 1H), 4.75 (dd, J = 2.4, 0.8Hz, 2H).

46%	Stage #1: 2-(prop-2-yn-1-yloxy)isoindoline-1,3-dione With hydrazine hydrate In diethyl ether at 20℃; for 2h; Stage #2: With hydrogenchloride In diethyl ether; water for 2h;	4.2.2. Synthesis of O-(propargyl)hydroxylamine hydrochloride (4) Compound 3 (1.0 mmol) was dissolved in diethyl ether (6 mL) and treated with hydrazine monohydrate (2.0 mmol). The reaction mixture was stirred for 2 h at rt Then, the solid residue was removed by filtration and HCl in ether (2 M, 4 mL) added to the filtrate with continuous stirring. The reaction was stirred for an additional 2 h and the resulting solid filtered and dried yielding 4 as a light yellow-solid (44 mg, 46%). Characterization data matches previously reported data.
36%	Stage #1: 2-(prop-2-yn-1-yloxy)isoindoline-1,3-dione With hydrazine hydrate In dichloromethane at 20℃; for 20h; Stage #2: With hydrogenchloride In 1,4-dioxane	48 O-Prop-2-ynyl-hydroxylamine hydrochloride (g): O-Prop-2-ynyl-hydroxylamine hydrochloride (g): A mixture of 2-prop-2-ynyloxy-isoindole-l,3-dione (f) (26.31 g, 130.78 mmol) and hydrazine monohydrate (12.7 mL, 261.56 mmol) in CH2CI2 (400 mL) was stirred at room temperature for 20 h. The reaction mixture was filtered. The filtrate was washed with water (100 mL), then with a brine solution (70 mL) and lastly dried over solid anhydrous Na2S04. A 4 M HCl/l,4-dioxane solution (34.0 mL, 136.00 mmol) was added, and the volatiles were removed under reduced pressure to yield O-prop-2-ynyl-hydroxylamine hydrochloride (g) (5.05 g, 36%). 400 MHz 1H NMR (DMSO-d6, ppm): δ 11.5-9.5 (2H, br s), 8.98 (1H, s), 4.76 (2H, d, J=2.4 Hz), 3.86 (1H, t, J=2.4Hz).
	With methylhydrazine In dichloromethane
	Stage #1: 2-(prop-2-yn-1-yloxy)isoindoline-1,3-dione With hydrazine In diethyl ether at 20℃; for 4h; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether	17 [00235] 0-(prop-2-yn-l-yl)hydroxylamine (LIV) was then prepared by removing the 1,2 compound by dissolving intermediate compound (LIII) in a solution of hydrazine in diethyl ether and stirring for 4 hours at ambient temperature under and inert gas atmosphere. 0-(prop-2-yn-l-yl)hydroxylamine (LIV): NMR (300M Hz, DMSO-d6): δ = 11.10 (br, 3H, +NJ0-), 4.75 (m, 2H, -OCJC≡CH), 3.87(m, 1H, - OCH2C≡Gfl). See FIG. 26. 13C NMR (75 MHz, DMSO-d6) : δ = 81.1, 76.5, 61.7. See FIG. 27.
3.70 g	With hydrogenchloride In water at 45 - 65℃;	1 In a 250mL three-necked flask ,added N, N- dimethylformamide (DMF((150mL), 3-bromo-1-propyne (11.9g, 0. 1mol) and N-hydroxy-phthalimide (16.3g, 0.1mol), after stirring to dissolving dropwise added triethylamine (12.2g,0.12mol).after the reaction was stirred at 40~60 ° C for 10~14hr it was cooled to room temperature,poured into ice water (500mL), filtered, washed with water to give N- propargyloxy phthalimide. then it heated at 45~65 ° C, With 37% concentrated hydrochloric acid (100mL) to give the the title compound as a pale yellow 3.70g, yield 34.4%.
	Stage #1: 2-(prop-2-yn-1-yloxy)isoindoline-1,3-dione With hydrazine hydrate at 20℃; for 0.5h; Stage #2: In diethyl ether at 20℃; for 2h; Stage #3: With hydrogenchloride In 1,4-dioxane; diethyl ether for 2h;

Reference： [1]Current Patent Assignee: CURACLE CO LTD - US2014/378399, 2014, A1 Location in patent: Paragraph 0093
[2]Location in patent: experimental part Banerjee, Deboshri; Liu, Allen P.; Voss, Neil R.; Schmid, Sandra L.; Finn [ChemBioChem, 2010, vol. 11, # 9, p. 1273 - 1279]
[3]Crane, Erika A.; Heydenreuter, Wolfgang; Beck, Katharina R.; Strajhar, Petra; Vomacka, Jan; Smiesko, Martin; Mons, Elma; Barth, Lydia; Neuburger, Markus; Vedani, Angelo; Odermatt, Alex; Sieber, Stephan A.; Gademann, Karl [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 12, p. 2508 - 2520]
[4]Rubio-Ruiz, Belén; Pérez-López, Ana M.; Sebastián, Víctor; Unciti-Broceta, Asier [Bioorganic and Medicinal Chemistry, 2021, vol. 41]
[5]Current Patent Assignee: GALLEON PHARMACEUTICALS - WO2014/78575, 2014, A2 Location in patent: Page/Page column 204-205
[6]Kim, Kyeojin; Maharjan, Sony; Lim, Changjin; Kim, Nam-Jung; Agrawal, Vijayendra; Han, Young Taek; Lee, Sujin; An, Hongchan; Yun, Hwayoung; Choi, Hyun-Jung; Kwon, Young-Guen; Suh, Young-Ger [European Journal of Medicinal Chemistry, 2014, vol. 75, p. 184 - 194]
[7]Current Patent Assignee: UNIVERSITY SYSTEM OF OHIO - WO2015/48728, 2015, A1 Location in patent: Paragraph 00235
[8]Current Patent Assignee: HUNAN HAILI CHEMICAL INDUSTRY COMPANY LIMITED - CN103965123, 2016, B Location in patent: Paragraph 0071; 0072; 0074
[9]Tang, Feng; Yang, Yang; Tang, Yubo; Tang, Shuai; Yang, Liyun; Sun, Bingyang; Jiang, Bofeng; Dong, Jinhua; Liu, Hong; Huang, Min; Geng, Mei-Yu; Huang, Wei [Organic and Biomolecular Chemistry, 2016, vol. 14, # 40, p. 9501 - 9518]

45
[ 6940-57-4 ]
[ 21663-79-6 ]
[ 1369588-27-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate; In ethanol; at 20℃; for 16h;	Preparation of fEM-f6-methyl-pyridin-2-yO-ethanone O-prop-2-ynyl-oxime2-Acetyl-6-methyl-pyridine (1.5g) was dissolved in ethanol (lOmL). Sodium acetate (1.37g) and O-propargyl-hydroxylamine hydrochloride (1.45g) were added. After stirring for 16h at ambient temperature the reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulphate, filtrated and evaporated to give a brown oil (1.9g). ^-NMR (CDCI3, 400 MHz):7.70 (d, 1H), 7.54 (t, 1H), 7.10 (d, 1H), 4.81 (s, 2H), 2.58 (s, 3H), 2.49 (s, 1H), 2.37 (s, 3H)
	With sodium acetate; In ethanol; at 20℃; for 16h;	Pre aration of E-l-(6-methyl-pyridin-2-yl)-ethanone O-prop-2-ynyl-oxime2-Acetyl-6-methyl-pyridine (1.5 g) was dissolved in ethanol (10 mL), and then Sodium acetate (1.37 g) and O-propargyl-hydroxylamine hydrochloride (1.45 g) were added. After stirring for 16h at ambient temperature the reaction mixture was diluted with ethyl acetate washed with water, dried over sodium sulfate, filtrated and evaporated to give a brown oil (1.9 g). ^-NMR (CDCI3, 400 MHz):7.70 (d, 1H), 7.54 (t, 1H), 7.10 (d, 1H), 4.81 (s, 2H), 2.58 (s, 3H), 2.49 (s, 1H), 2.37 (s, 3H)

Reference： [1]Patent: WO2012/38521,2012,A1 .Location in patent: Page/Page column 140
[2]Patent: WO2012/62844,2012,A1 .Location in patent: Page/Page column 108-109

46
[ 959864-55-2 ]
[ 21663-79-6 ]
(E)-4-(4-(1-(prop-2-ynyloxyimino)ethyl)phenyl)-1,2,4-triazolidine-3,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%	With hydrogenchloride In 1,4-dioxane; ethanol at 50℃; for 2h;	6 Preparation of Intermediate (E)-4-(4-(1-(prop-2-ynyloxyimino)eth yI)phenyl)- 1,2, 4-triazolidine-3, 5- dione (I-6a): Preparation of Intermediate (E)-4-(4-(1-(prop-2-ynyloxyimino)eth yI)phenyl)- 1,2, 4-triazolidine-3, 5- dione (I-6a):To 4-(4-acetylphenyl)-1,2,4-triazolidine-3,5-dione (500 mg, 2.281 mmol) in ethanol (6.912 mL) was added O-(prop-2-ynyl)hydroxylamine hydrochloride (368 mg, 3.42 mmol) and HCI 4N in dioxane (1.711 mL, 6.84 mmol). The mixture was stirred at 50°C for 2 hours and then concentrated in vacuo. Saturated sodium bicarbonate was added, extracted with ethyl acetate twice, dried over Mg504, filtered, and concentrated in vacuo. The residue was purified by silicagel chromatography (60-100% ethyl acetate/heptane, and then 5% MeOHethyl acetate) giving (E)-4-(4-(1 -(prop-2-ynyloxyimino)ethyl)phenyl)-1 ,2,4-triazolidine-3,5-dione c-6a: 46 mg, 7%) as a white solid. LC-MS (M+1) 273.1, t = 0.81 minute. 1H NMR (400 MHz, DMSO-d6) 6 ppm 2.23 (s, 3 H) 3.48 (t, J=2.40 Hz, 1 H) 4.80 (d, J=2.27 Hz, 2 H) 7.53 (d, J=8.59 Hz, 2 H) 7.76 (d, J=8.59 Hz, 2 H) 10.52 (s, 2 H).

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2013/9564, 2013, A1 Location in patent: Page/Page column 71

47
[ 1446092-98-3 ]
[ 21663-79-6 ]
((2R,3S)-3-acetoxy-6-((3S,10R,13S,17S)-10,13-dimethyl-17-((E)-1-(prop-2-ynyloxyimino)ethyl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxy)-3,6-dihydro-2H-pyran-2-yl)methyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine for 3h; Reflux;	General synthetic procedure for preparation of oxime analogs (21a-r) General procedure: O-Alkyl or aryl hydroxylamineHCl (1.2 equiv) was added to asolution of 20 (1 equiv) in pyridine (3 mL). The reaction mixture was refluxed for 3 h, cooled to room temperature, and quenched with 2 N HCl, and diluted with diethylether. The organic phase was dried over MgSO4, and concentrated in vacuo. Purification of the residue via flash column chromatography on silica gel (EtOAc:n-Hexane 1:10) afforded the corresponding oxime analogs.

Reference： [1]Kim, Kyeojin; Maharjan, Sony; Lim, Changjin; Kim, Nam-Jung; Agrawal, Vijayendra; Han, Young Taek; Lee, Sujin; An, Hongchan; Yun, Hwayoung; Choi, Hyun-Jung; Kwon, Young-Guen; Suh, Young-Ger [European Journal of Medicinal Chemistry, 2014, vol. 75, p. 184 - 194]

48
[ 21663-79-6 ]
[ 501-53-1 ]
O-benzyl-N-prop-2-ynyloxycarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 14h;	48 O-Benzyl-N-prop-2-ynyloxy-carbamate (h): O-Benzyl-N-prop-2-ynyloxy-carbamate (h): To a pre-cooled, 0°C solution of O-prop-2-ynyl-hydroxylamine hydrochloride (g) (5.00 g, 46.49 mmol) in CH2C12 (200 mL) was added N,N- diisopropyl ethylamine (20.1 mL, 116.23 mmol) and benzyl chloroformate (7.0 mL, 46.49 mmol). The resulting solution was stirred at ambient temperature for 14 h. The reaction mixture was then washed with saturated aqueous NaHC( solution (2 x 50 mL), then with water (50 mL) and lastly, dried over solid anhydrous Na2S04. The volatiles were removed under vacuum to yield O-benzyl-N-prop-2-ynyloxy- carbamate (h) (8.06 g , 84%). 400 MHz 1H NMR (CDC13, ppm): δ 7.39-7.30 (5H, m), 5.19 (2H, s), 5.17 (1H, s), (2H, d, J=2.4 Hz), 2.50 (1H, t, J=2.4 Hz).

Reference： [1]Current Patent Assignee: GALLEON PHARMACEUTICALS - WO2014/78575, 2014, A2 Location in patent: Page/Page column 204-205

49
[ 21663-79-6 ]
[ 3071-66-7 ]
[ 1610534-59-2 ]

Yield	Reaction Conditions	Operation in experiment
34%	With sodium hydroxide In 1,4-dioxane at 90℃; for 8h;	49 Example 49: N-(4,6-Bis-n-propylamino-[l,3,51triazin-2-yl)-0-prop-2-vnyl- hydroxylamine (121) and corresponding hydrochloride salt (122a) (Scheme 44) N-( 4, 6-Bis-n-propylamino-[ 1, 3, 5 ]triazin-2-yl)-0-prop-2-ynyl-hydroxylamine (121): Example 49: N-(4,6-Bis-n-propylamino-[l,3,51triazin-2-yl)-0-prop-2-vnyl- hydroxylamine (121) and corresponding hydrochloride salt (122a) (Scheme 44) N-( 4, 6-Bis-n-propylamino-[ 1, 3, 5 ]triazin-2-yl)-0-prop-2-ynyl-hydroxylamine (121): A mixture of 6-chloro-N,N'-n-dipropyl-[l,3,5]triazine-2,4-diamine (20) (300 mg, 1.31 mmol), O-prop-2-ynyl-hydroxylamine hydrochloride (g) (323 mg, 3.00 mmol) and NaOH (120 mg, 3.00 mmol) in 1,4-dioxane (5 mL) was heated at 90°C for 8 h. The mixture was cooled to ambient temperature. A saturated NaHC( solution (15 mL) was added and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic extracts were washed with water (30 mL), then with a brine solution (30 mL) and lastly, dried over solid anhydrous Na2S04. The solvent was removed under reduced pressure and the resultant residue was purified by flash column chromatography using gradient elution from CE^C^/EtOH (99:1) to CH2Cl2/EtOH (9:1) to yield N-(4,6-bis-n-propylamino-[l,3,5]triazin-2-yl)-0-prop-2- ynyl-hydroxylamine hydrochloride (121) (118 mg, 34%). 400 MHz *Η NMR (CDC13, ppm): δ 7.73 (IH, br s), 5.14-4.92 (2H, m), 4.60 (2H, s), 3.41-3.25 (4H, m), 2.50 (IH, t, J=2.4 Hz), 1.58 (4H, sextet, J=7.3 Hz), 0.95 (6H, t, J=7.3 Hz). ESI-MS (m/z): 265 [M+H]+.

Reference： [1]Current Patent Assignee: GALLEON PHARMACEUTICALS - WO2014/78575, 2014, A2 Location in patent: Page/Page column 207

50
[ 1446092-98-3 ]
[ 21663-79-6 ]
C₃₄H₄₇NO₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine at 80℃; for 2h; Inert atmosphere;	1-2 Preparation of SAC-1010 After 500 mg of hydroxyphthalimide (Aldrich) was dissolved in 5 ml of dimethylformamide under argon flow, 501 mg of propargyl bromide (Aldrich) was added, and 0.5 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene (Aldrich) was slowly added. After the mixture was stirred at 60° C. for 2 hours, the temperature was again lowered to room temperature, and then the reaction was stopped by adding a 2 N hydrochloric acid solution. The reaction liquid was diluted by adding 20 ml of ethyl acetate, followed by drying over magnesium sulfate and then filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixed eluent of ethyl acetate/hexane (1:5) and then dried to obtain 396 mg of a white solid (yield: 64%). The white solid was dissolved in 5 ml of dichloromethane, and 0.17 ml of methyl hydrazine (TCI) was slowly added at 0° C. After the reaction liquid was stirred at room temperature for 2 hours, the temperature was again lowered to 0° C. The generated solid was then filtered out, and 1 ml of a 4 M-hydrochloric acid dioxane solution (Aldrich) was added to the residual filtrate, followed by filtration and drying, to obtain 230 mg of a solid (yield: 100%). 13 mg of the obtained solid and 55 mg of SAC-0906 obtained as obtained above were dissolved in 1 ml of pyridine (Aldrich) under argon flow, followed by stirring at 80° C. for 2 hours. After the temperature was lowered to room temperature, the reaction liquid was acidified by adding a 2 N hydrochloric acid solution, followed by extraction with 20 ml of diethyl ether, drying over magnesium sulfate, and filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixed eluent of ethyl acetate/hexane (1:5) to obtain the target compound SAC-1010 (53 mg, yield: 88%). 1H-NMR (300 MHz, CDCl3) δ5.92-5.76 (m, 2H), 5.34-5.33 (m, 1H), 5.28-5.25 (m, 1H), 5.15 (m, 1H), 4.61 (d, J=2.4 Hz, 2H), 4.25-4.05 (m, 3H), 3.68-3.41 (m, 1H), 2.42-0.62 (m, 36H)

Reference： [1]Current Patent Assignee: CURACLE CO LTD - US2014/378399, 2014, A1 Location in patent: Paragraph 0091; 0093

51
(R)-2-(4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)propionic acid chloride [ No CAS ]
[ 21663-79-6 ]
(R)-2-(4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)-Ν-(2-propargyloxy)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30.2%	With dmap; triethylamine In dichloromethane Cooling with ice;	1 preparation method of compound 01 In a three-necked flask, add toluene (40mL), (R)-2-(4-((6- Chloro-quinoxalin-2-yl)oxy) phenoxy) propanoic acid (II-C1)( 1.15g,3.3mmol)andThionyl chloride (1 · 19g, 10mmol) and after reflux for 3-4hr remove excess of Thionylchloride and toluene to obtain (R)-2-(4-((6- Chloro-quinoxalin-2-yl) oxy)propionic acid chloride. The above mentioned acid chloride was added in dichloromethane (40mL), 0- PropargylHydroxylamine hydrochloride(III-1)(0.36g,3.3mmol) and DMAP (0.2g)then stirred at ice bath and dropwise added triethylamine(0.1g,10mmol). After stirring the reaction mixture for 1~3hr it was poured into ice water (200ml) andextracted with dichloromethane. The organic phase was washed with water, driedover anhydrous sodium sulfate then solvent removal and by column chromatography (V petroleum ether /ethyl acetate = 2: 1) to obtain 0.40g ofthe title compound as a white solid (Compound 01 in Table 1), a yield of 30.2%.

Reference： [1]Current Patent Assignee: HUNAN HAILI CHEMICAL INDUSTRY COMPANY LIMITED - CN103965123, 2016, B Location in patent: Paragraph 0071; 0072; 0075

52
(2R)-2-{4-[(6-chloro-1,3-benzoxazol-2-yl)oxy]phenoxy}propanoyl chloride [ No CAS ]
[ 21663-79-6 ]
(R)-2-(4-((6-chlorobenzo[d]oxazol-2-yl)oxy)phenoxy)-N-(2-propargyl)propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42.7%	With dmap; triethylamine In dichloromethane Cooling with ice;	7 preparation method of compound 07 (R)-2-(4-((6- Chlorobenzo [(d] oxazol-2-yl) oxy) phenoxy) -Ν- (2- propargyloxy)propionamide (Table 1, 07) in a 100mL three-necked flask was added toluene(40mL),(R)-2-(4-((6 - Chlorobenzo [(d] oxazol-2-yl) oxy) phenoxy) propanoic acid (II-C2 )( 1.11g3.3mmol) and Thionyl chloride (1.19g, 10mmol), after it was refluxed 3~5hr remove excess of Thionyl chloride and toluene to obtain (R)-2-(4-((6- Chlorobenzo [(d] oxazol-2-yl) oxy) phenoxy) propionic acid chloride. The above mentioned acid chloride was added in dichloromethane (40mL), 0- PropargylHydroxylamine hydrochloride (III-1)(0.36g,3.3mmol) and DMAP (0.2g)then stirred at ice bath and dropwise added triethylamine (0.1g,10mmol). After stirring the reaction mixture for 1~3hr it was poured into ice water (200ml) and extracted with dichloromethane. The organic phase was washed with water, dried over anhydrous sodium sulfate then solvent removal and by column chromatography (V petroleum ether /ethyl acetate = 3: 1) to obtain 0.55g of the title compound as a white solid (Compound 07 in Table 1), a yield of 42.7%.

Reference： [1]Current Patent Assignee: HUNAN HAILI CHEMICAL INDUSTRY COMPANY LIMITED - CN103965123, 2016, B Location in patent: Paragraph 0097; 0098; 0100

53
[ 67-56-1 ]
[ 156-39-8 ]
[ 21663-79-6 ]
(E)-3-(4-hydroxyphenyl)-2-[(2-propyn-1-yloxy)imino]propanoic acid [ No CAS ]
methyl (E)-3-(4-hydroxyphenyl)-2-[(2-propyn-1-yloxy)imino]propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 64% 2: 28%	In dichloromethane at 20℃; for 20h;	(E)-3-(4-hydroxyphenyl)-2-[(2-propyn-1-yloxy)imino]propanoic acid (4a) and methyl (E)-3-(4-hydroxyphenyl)-2-[(2-propyn-1-yloxy)imino]propanoate (4b) To a solutionof 4-hydroxyphenylpyruvic acid (1) (500 mg, 2.8 mmol) inCH2Cl2-MeOH (2 : 1 v/v) (28 mL) was added 3 (602 mg,5.6 mmol) at room temperature. After stirring for 20 h, thereaction mixture was concentrated, and the residue was purifiedby flash column chromatography (CHCl3-MeOH=50 : 1to 10 : 1) to selectively afford (E)-oxime44) (4a) (420 mg,64%) as a colorless powder and (E)-oxime-methyl ester (4b)(194 mg, 28%) as a colorless powder, respectively (Chart 4).For 4a: mp 137-139°C; IR (KBr) νmax (cm-1): 3487, 3255,2121, 1712, 1604, 1512, 1435, 1357, 1257, 1219, 1126; 1H-NMR(500 MHz, CD3OD) δ (ppm): 7.08 (d, 2H, J=8.6 Hz), 6.67 (d,2H, J=8.6 Hz), 4.86 (2H, d, J=2.3 Hz), 3.80 (2H, s), 2.97 (1H,t, J=2.3 Hz); 13C-NMR (125 MHz, CD3OD) δ (ppm): 165.8,157.2, 153.9, 131.1 (2C), 127.7, 116.2 (2C), 79.7, 76.9, 63.7,31.0; HR-MS (electrospray ionization (ESI)) m/z: 256.0575[M+Na]+; Calcd for C12H11NO4Na, 256.0580. For 4b: mp79-82°C; IR (KBr) νmax (cm-1): 3433, 3278, 2121, 1728, 1604,1512, 1442, 1365, 1326, 1227, 1134; 1H-NMR (500 MHz,CD3OD) δ (ppm): 7.06 (d, 2H, J=8.4 Hz), 6.67 (d, 2H,J=8.4 Hz), 4.85 (2H, d, J=2.3 Hz), 3.82 (2H, s), 3.78 (3H, s),2.97 (1H, t, J=2.3 Hz); 13C-NMR (125 MHz, CD3OD) δ (ppm):165.0, 157.2, 153.4, 131.1 (2C), 127.5, 116.2 (2C), 79.7, 76.9,63.8, 53.0, 31.2; HR-MS (ESI) m/z: 270.0732 [M+Na]+; Calcdfor C13H13NO4Na, 270.0737.

Reference： [1]Toguchi, Shohei; Hirose, Tomoyasu; Yorita, Kazuko; Fukui, Kiyoshi; Sharpless, K. Barry; Omura, Satoshi; Sunazuka, Toshiaki [Chemical and Pharmaceutical Bulletin, 2016, vol. 64, # 7, p. 695 - 703]

54
[ 67-56-1 ]
[ 4228-66-4 ]
[ 21663-79-6 ]
(E)-3-(3,4-dihydroxyphenyl)-2-[(2-propyn-1-yl oxy)-imino]propanoic acid [ No CAS ]
methyl (E)-3-(3,4-dihydroxyphenyl)-2-[(2-propyn-1-yloxy)imino]propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%; 24%	In dichloromethane; at 20.0℃; for 20.0h;	General procedure: To a solutionof 4-hydroxyphenylpyruvic acid (1) (500 mg, 2.8 mmol) inCH2Cl2-MeOH (2 : 1 v/v) (28 mL) was added 3 (602 mg,5.6 mmol) at room temperature. After stirring for 20 h, thereaction mixture was concentrated, and the residue was purifiedby flash column chromatography (CHCl3-MeOH=50 : 1to 10 : 1) to selectively afford (E)-oxime44) (4a) (420 mg,64%) as a colorless powder and (E)-oxime-methyl ester (4b)(194 mg, 28%) as a colorless powder, respectively (Chart 4).

Reference： [1]Chemical and Pharmaceutical Bulletin,2016,vol. 64,p. 695 - 703

55
C₁₀₈H₁₇₇N₁₅O₆₆ [ No CAS ]
[ 21663-79-6 ]
C₁₁₄H₁₈₃N₁₇O₆₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86.6%	In aq. phosphate buffer at 20℃; for 2h;

Reference： [1]Tang, Feng; Yang, Yang; Tang, Yubo; Tang, Shuai; Yang, Liyun; Sun, Bingyang; Jiang, Bofeng; Dong, Jinhua; Liu, Hong; Huang, Min; Geng, Mei-Yu; Huang, Wei [Organic and Biomolecular Chemistry, 2016, vol. 14, # 40, p. 9501 - 9518]

56
N-(dimethylaminomethylene)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide [ No CAS ]
[ 21663-79-6 ]
N-[(Z)-prop-2-ynoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl] benzamide [ No CAS ]
N-[(E)-prop-2-ynoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl] benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: O-(prop-2-yn-1-yl)hydroxylamine hydrochloride With triethylamine In dichloromethane at 20℃; for 0.0833333h; Stage #2: N-(dimethylaminomethylene)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide In dichloromethane at 20℃; for 16h;	4a.2; 4b.2 Step 2: Preparation N-[(Z)-prop-2-vnoxyiminomethyl)-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yll benzamide dichloromethane (4.0 mL) under an atmosphere of nitrogen was added triethylamine (0.27 mL, 1.92 mmol) at room temperature. After 5 minutes crude N-(dimethylaminomethylene)-4-[5-(trifluoromethyl)- 1 ,2,4-oxadiazol-3-yl] benzamide (0.6 g, 1.92 mmol) was added. The reaction mixture was allowed to react for 16 hours at room temperature. The organic phase was washed with 1 N NaOH (3.5 mL) and dried over sodium sulfate. The solvent was removed under reduced pressure. The crude residue was subjected to flash chromatography over silica gel (dichloromethane:diisopropyl ether eluent 1 :99) to afford a 4: 1 E/Z-mixture of N-[(E/Z)-prop-2-ynoxyiminomethyl)-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl] benzamide. N-[(Z)-prop-2-ynoxyiminomethyl]-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl] benzamide (melting point: 1 14-1 19°C) - NMR (400 MHz, CDCI3) 5 ppm: 8.89 (d, 1 H), 8.27 (d, 2H), 8.02 (d, 2H), 7.93 (d, 1 H), 4.73 (d, 2H), 2.53 (t, 1 H). N-[(E)-prop-2-ynoxyiminomethyl)- 4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl] benzamide - H NMR (400 MHz, CDCI3) δ ppm: 8.71 (d, 1 H), 8.25 (d, 2H), 8.01 (d, 2H), 7.93 (d, 1 H), 4.60 (d, 2H), 2.51 (t, 1 H). Example 5: Preparation of N-[3-ethoxyiminopropyl]-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]benzamide (Compound 1.153 of Table T1

Reference： [1]Current Patent Assignee: Syngenta (in: Sinochem Holdings); SINOCHEM HOLDINGS CORPORATION LTD - WO2017/207757, 2017, A1 Location in patent: Page/Page column 59

57
32(R)-methoxyrapamycin [ No CAS ]
[ 21663-79-6 ]
32(R)-methoxy-26-O-(prop-2-yn-1-yl)oxime rapamycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50.2%	With pyridine; hydrogenchloride In 1,4-dioxane; water at 50℃; for 108h;	3 Step 3: Synthesis of 32(R)-methoxy-26-O-(prop-2-yn-l-yl) oxime rapamycin [00422] To a solution of 32(R)-methoxy rapamycin (780.0 mg, 0.838 mmol, 1.0 equiv) and 3-(aminooxy)prop-l-yne hydrochloride (450.9 mg, 4.192 mmol, 5.0 equiv) in pyridine (3.9 mL) was added dropwise HC1 in 1,4-dioxane (4 M, 1.46 mL, 5.84 mmol, 7.0 equiv) over 1 min at room temperature. The reaction mixture was then heated at 50 °C for 36 h. Additional 3-(aminooxy)prop-l-yne hydrochloride (90.17 mg, 0.838 mmol, 1.0 equiv) and HCl in 1,4-dioxane (4 M, 1.04 mL, 4.16 mmol, 5.0 equiv) were added after the reaction had been cooled to room temperature. The reaction mixture was again heated at 50 °C and stirred for 72 h. The reaction mixture was added dropwise into H2O (70 mL) and cooled at 0 °C. The resulting solid was filtered off, washed with H2O, and purified by silica gel chromatography (0→60% EtOAc/hexanes). The desired product was lyophilized to a white solid (414 mg, 50.2% yield, mixture of E/Z isomers). LCMS (ESI) m/z: [M + H2O] calcd for C55H86N2O13: 1000.6; found 1000.5.

Reference： [1]Current Patent Assignee: REVOLUTION MEDICINES INC - WO2018/204416, 2018, A1 Location in patent: Paragraph 00422

58
32(R)-ethoxy rapamycin [ No CAS ]
[ 21663-79-6 ]
32(R)-ethoxy-26-O-(prop-2-yn-1-yl)oxime rapamycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With pyridine; hydrogenchloride In 1,4-dioxane at 50℃; for 72h;	3 Step 3: Synthesis of 32(R)-ethoxy-26-O-(prop-2-yn-l-yl) oxime rapamycin [00495] To a solution of 32(R)-ethoxy rapamycin (1.49 g, 1.53 mmol, 1.0 equiv) and 3- (aminooxy)prop-l-yne hydrochloride (849 mg, 7.89 mmol, 5.2 equiv) in pyridine (7.5 mL) was added 4M HC1 in 1,4-dioxane (2.76 mL, 11.04 mmol, 7.2 equiv), dropwise. The reaction mixture was then heated to 50 °C for 3 days. The mixture was cooled to ambient temperature and then added dropwise to H2O. The resulting solids were filtered, washed with H2O and taken up in EtOAc. The organic layer was washed sequentially with 1 M HC1, sat. NaHCCb solution, and brine, dried over Na2S04, and concentrated to a thick viscous oil. The oil was purified by silica gel chromatography (2:3→4: 1 EtOAc/hexanes) to afford the desired product as a white solid (640 mg, 42% yield, mixture of E/Z isomers). LCMS (ESI) m/z: [M + Na] calcd for C56H88N2O13: 1019.62; found 1019.8.

Reference： [1]Current Patent Assignee: REVOLUTION MEDICINES INC - WO2018/204416, 2018, A1 Location in patent: Paragraph 00495

59
[ 21663-79-6 ]
32(R)-hydroxyrapamycin [ No CAS ]
32(R)-hydroxy-26-O-(prop-2-yn-1-yl)oxime rapamycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With pyridine; hydrogenchloride; methanol In 1,4-dioxane at 50℃; for 72h;	Monomer 6. Synthesis of 32(R)-hydroxy-26-0-(prop-2-yn-l-yl) oxime rapamycin . [00425] To a dry reaction flask was added 32(R)-hydroxy rapamycin (2.74 g, 2.99 mmol, 1.0 equiv) and 3-(aminooxy)prop-l-yne hydrochloride (1.608 g, 14.95 mmol, 5.0 equiv), followed by pyridine (13.9 mL, 172 mmol, 57.5 equiv). 4M HC1 in dioxane (7.48 mL, 29.9 mmol, 10 equiv) was added dropwise over 1 min and then the reaction was heated to 50 °C. MeOH (3.5 mL, 86 mmol, 29 equiv) was added after the reaction mixture reached 50 °C and the solution was stirred for 72 h. The reaction mixture was concentrated under reduced pressure to ~5 mL total volume before being added dropwise to H2O (50 mL). Solids precipitated from solution and then the mixture was decanted to remove the aqueous layer and the remaining material was washed with H2O (25 mL). The crude solid was dissolved in EtOAc (50 mL) and washed with 1M HC1 (25 mL), sat. NaHC03 (25 mL), and brine (25 mL). The organic phase was concentrated under reduced pressure to provide a yellow foam. Purification by chromatography on silica gel (0→60% EtOAc/hexanes) afforded the product as a yellow foam (1.49 g, 45% yield, mixture of E/Z isomers). LCMS (ESI) m/z: [M + H] calc for C54H84N2O13: 969.61; found 969.8.

Reference： [1]Current Patent Assignee: REVOLUTION MEDICINES INC - WO2018/204416, 2018, A1 Location in patent: Paragraph 00425

60
[ 21663-79-6 ]
[ 53123-88-9 ]
C₅₄H₈₂N₂O₁₃ [ No CAS ]
C₅₄H₈₂N₂O₁₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate In methanol at 20℃; for 72h;	[00487] To a solution of rapamycin (200.0 mg, 0.219 mmol, 1 equiv) in MeOH (5.00 mL) was added sequentially sodium acetate (0.0718 g, 0.875 mmol) and 3-(aminooxy)prop-l-yne hydrochloride (0.0941 g, 0.875 mmol, 4.0 equiv) at room temperature. The reaction was stirred at room temperature for 72 h. The reaction mixture was diluted with EtOAc (20 mL) and washed with 20 mL portions of H2O and brine. The solution was dried over Na2S04, filtered, and concentrated. The resulting residue was purified via combiflash chromatography (0→80% EtO Ac/hex) to yield the Z isomer followed by the E isomer, both as colorless oils. Both products were taken up separately in 95% aq MeCN and lyophilized to white powders. Z isomer: LCMS (ESI) m/z: [M + Na] calcd for 989.57; found 989.5. E isomer: LCMS (ESI) m/z [M + Na] calcd for found 989.5.

Reference： [1]Current Patent Assignee: REVOLUTION MEDICINES INC - WO2018/204416, 2018, A1 Location in patent: Paragraph 00487

61
6-methoxy-(R)-4-[((1S,2S,4S)-5-oxo-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl]quinoline [ No CAS ]
[ 21663-79-6 ]
6-methoxy-(R)-4-[((1S,2S,4S,5Z/E)-5-propargyloxyimino-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	In methanol for 1h; Reflux;

Reference： [1]Wang, Xu; Zeng, Yuna; Sheng, Li; Larson, Peter; Liu, Xue; Zou, Xiaowen; Wang, Shufang; Guo, Kaijing; Ma, Chen; Zhang, Gang; Cui, Huaqing; Ferguson, David M.; Li, Yan; Zhang, Jingren; Aldrich, Courtney C. [Journal of Medicinal Chemistry, 2019, vol. 62, # 5, p. 2305 - 2332]

62
[ 1334232-69-7 ]
[ 21663-79-6 ]
(R)-6-((R)-1-hydroxy-1-((4aR,4bS,6aS,7S,9aS,9bS,9cS,10aS,10bR,E)-10b-hydroxy-4a,6a-dimethyl-2-((prop-2-yn-1-yloxy)imino)-2,4a,4b,5,6,6a,7,8,9,9a,9b,9c,10a,10b-tetradecahydro-1H-cyclopenta[1,2]phenanthro[9,10-b]oxiren-7-yl)ethyl)-3,4-dimethyl-5,6-dihydro-2H-pyran-2-one [ No CAS ]
(R)-6-((R)-1-hydroxy-1-((4aR,4bS,6aS,7S,9aS,9bS,9cS,10aS,10bR)-10b-hydroxy-4a,6a-dimethyl-2-((prop-2-yn-1-yloxy)imino)-2,4a,4b,5,6,6a,7,8,9,9a,9b,9c,10a,10b-tetradecahydro-1H-cyclopenta[1,2]phenanthro[9,10-b]oxiren-7-yl)ethyl)-3,4-dimethyl-5,6-dihydro-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 70℃; for 4h; Overall yield = 86 %;	General procedure A for oxime ethers 5-7 General procedure: To a solution of ketone (1.0 equiv.) in pyridine (freshly distilled overKOH pellets, 1.0 equiv.) was added the O-propargyl hydroxylaminehydrochloride (S4, 3.0 equiv, see Supporting information for syntheticdetails of S4) in an oven-dried round-bottom flask with stir bar(equipped with oven-dried reflux condenser), and the mixture washeated at 70 °C for the indicated time. The solvent was then removedunder high vacuum, and the resulting residue was dissolved in CH2Cl2.Saturated NH4Cl (aqueous) solution was added and the aqueous phasewas extracted with CH2Cl2 (3×). The combined organic phases weredried over Na2SO4, filtered and concentrated in vacuo. The crude productwas purified by flash column chromatography under the indicatedconditions to yield the oxime ethers 5-7.

Reference： [1]Crane, Erika A.; Heydenreuter, Wolfgang; Beck, Katharina R.; Strajhar, Petra; Vomacka, Jan; Smiesko, Martin; Mons, Elma; Barth, Lydia; Neuburger, Markus; Vedani, Angelo; Odermatt, Alex; Sieber, Stephan A.; Gademann, Karl [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 12, p. 2508 - 2520]

63
[ 1334232-69-7 ]
[ 21663-79-6 ]
(R)-6-((R)-1-hydroxy-1-((4aR,4bS,6aS,7S,9aS,9bS,9cS,10aS,10bR,E)-10b-hydroxy-4a,6a-dimethyl-2-((prop-2-yn-1-yloxy)imino)-2,4a,4b,5,6,6a,7,8,9,9a,9b,9c,10a,10b-tetradecahydro-1H-cyclopenta[1,2]phenanthro[9,10-b]oxiren-7-yl)ethyl)-3,4-dimethyl-5,6-dihydro-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With pyridine at 70℃; for 72h;	General procedure A for oxime ethers 5-7 General procedure: To a solution of ketone (1.0 equiv.) in pyridine (freshly distilled overKOH pellets, 1.0 equiv.) was added the O-propargyl hydroxylaminehydrochloride (S4, 3.0 equiv, see Supporting information for syntheticdetails of S4) in an oven-dried round-bottom flask with stir bar(equipped with oven-dried reflux condenser), and the mixture washeated at 70 °C for the indicated time. The solvent was then removedunder high vacuum, and the resulting residue was dissolved in CH2Cl2.Saturated NH4Cl (aqueous) solution was added and the aqueous phasewas extracted with CH2Cl2 (3×). The combined organic phases weredried over Na2SO4, filtered and concentrated in vacuo. The crude productwas purified by flash column chromatography under the indicatedconditions to yield the oxime ethers 5-7.

Reference： [1]Crane, Erika A.; Heydenreuter, Wolfgang; Beck, Katharina R.; Strajhar, Petra; Vomacka, Jan; Smiesko, Martin; Mons, Elma; Barth, Lydia; Neuburger, Markus; Vedani, Angelo; Odermatt, Alex; Sieber, Stephan A.; Gademann, Karl [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 12, p. 2508 - 2520]

64
[ 1334232-74-4 ]
[ 21663-79-6 ]
(R)-6-((R)-1-hydroxy-1-((4aR,4bS,6aS,7S,9aS,9bS,9cS,10aS,10bR,Z)-10b-hydroxy-4a,6a-dimethyl-2-((prop-2-yn-1-yloxy)imino)hexadecahydro-1H-cyclopenta[1,2]phenanthro[9,10-b]oxiren-7-yl)ethyl)-3,4-dimethyl-5,6-dihydro-2H-pyran-2-one [ No CAS ]
(R)-6-((R)-1-hydroxy-1-((4aR,4bS,6aS,7S,9aS,9bS,9cS,10aS,10bR)-10b-hydroxy-4a,6a-dimethyl-2-((prop-2-yn-1-yloxy)imino)hexadecahydro-1H-cyclopenta[1,2]phenanthro[9,10-b]oxiren-7-yl)ethyl)-3,4-dimethyl-5,6-dihydro-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20 % de	With pyridine at 70℃; for 5h; Overall yield = > 99 %; Overall yield = 4.1 mg;	General procedure A for oxime ethers 5-7 General procedure: To a solution of ketone (1.0 equiv.) in pyridine (freshly distilled overKOH pellets, 1.0 equiv.) was added the O-propargyl hydroxylaminehydrochloride (S4, 3.0 equiv, see Supporting information for syntheticdetails of S4) in an oven-dried round-bottom flask with stir bar(equipped with oven-dried reflux condenser), and the mixture washeated at 70 °C for the indicated time. The solvent was then removedunder high vacuum, and the resulting residue was dissolved in CH2Cl2.Saturated NH4Cl (aqueous) solution was added and the aqueous phasewas extracted with CH2Cl2 (3×). The combined organic phases weredried over Na2SO4, filtered and concentrated in vacuo. The crude productwas purified by flash column chromatography under the indicatedconditions to yield the oxime ethers 5-7.

Reference： [1]Crane, Erika A.; Heydenreuter, Wolfgang; Beck, Katharina R.; Strajhar, Petra; Vomacka, Jan; Smiesko, Martin; Mons, Elma; Barth, Lydia; Neuburger, Markus; Vedani, Angelo; Odermatt, Alex; Sieber, Stephan A.; Gademann, Karl [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 12, p. 2508 - 2520]

65
[ 33428-64-7 ]
[ 21663-79-6 ]
(R)-6-((R)-1-hydroxy-1-((4aS,4bS,6aS,7S,9aS,9bS,9cS,10aS,10bR,E)-10b-hydroxy-4a,6a-dimethyl-4-((prop-2-yn-1-yloxy)imino)hexadecahydro-1H-cyclopenta[1,2]phenanthro[9,10-b]oxiren-7-yl)ethyl)-3,4-dimethyl-5,6-dihydro-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With pyridine at 70℃; for 7h;	General procedure A for oxime ethers 5-7 General procedure: To a solution of ketone (1.0 equiv.) in pyridine (freshly distilled overKOH pellets, 1.0 equiv.) was added the O-propargyl hydroxylaminehydrochloride (S4, 3.0 equiv, see Supporting information for syntheticdetails of S4) in an oven-dried round-bottom flask with stir bar(equipped with oven-dried reflux condenser), and the mixture washeated at 70 °C for the indicated time. The solvent was then removedunder high vacuum, and the resulting residue was dissolved in CH2Cl2.Saturated NH4Cl (aqueous) solution was added and the aqueous phasewas extracted with CH2Cl2 (3×). The combined organic phases weredried over Na2SO4, filtered and concentrated in vacuo. The crude productwas purified by flash column chromatography under the indicatedconditions to yield the oxime ethers 5-7.

Reference： [1]Crane, Erika A.; Heydenreuter, Wolfgang; Beck, Katharina R.; Strajhar, Petra; Vomacka, Jan; Smiesko, Martin; Mons, Elma; Barth, Lydia; Neuburger, Markus; Vedani, Angelo; Odermatt, Alex; Sieber, Stephan A.; Gademann, Karl [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 12, p. 2508 - 2520]

66
5-hydroxy-2,6-dimethyl-4(1-naphthalenylcarbonyl)-3(2H)-pyridazinone [ No CAS ]
[ 21663-79-6 ]
5-hydroxy-2,6-dimethyl-4-[(E)-(2-propyn-1-yloxy)imino-1-naphthalenylmethyl]-3(2H)-pyridazinone [ No CAS ]
5-hydroxy-2,6-dimethyl-4-[(Z)-(2-propyn-1-yloxy)imino-1-naphthalenylmethyl]-3(2H)-pyridazinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 2.3 g 2: 3.1 g	With sodium hydrogencarbonate In methanol at 45℃;	2.D Step D: Preparation of 5-hydroxy -2, 6-dimethyl-4-[(Z?)-[(2-propyn-l-yloxy )imino]-l - naphthalenylmethyl]-3(2T/)-pyridazinone and 5-hydroxy-2,6-dimethyl-4-[(Z)- [(2-propyn-l-yloxy)imino]-l-naphthalenylmethyl]-3(2/ )-pyridazinone To a solution of 5-hydroxy-2,6-dimethyl-4-(l-naphthalenylcarbonyl)-3(2fl)- pyndazinone (i.e. the product from Step C) (5.8 g, 19.71 mmol) and sodium bicarbonate (2.48 g, 29.56 mmol) in 50 mL of methanol was added 0-2-propargylhydroxylamine hydrochloride (4.24 g, 39.42 mmol). The reaction mixture was heated at 45 °C over the weekend and partitioned between water and dichloromethane. The aqueous phase was extracted with additional dichloromethane and the combined organic phases were washed with brine. The organic phase was dried over magnesium sulfate, filtered, and concentrated under vacuum. The crude material was purified via silica gel chromatography using ethyl acetate in dichloromethane as the solvent gradient to provide 2 3 g the T’-isomer and 3.1 g of the Z-isomer. E-isomer 1H NMR12.37 (s, 11 1). 7.85-7.92 (m, 21 1 ). 7.62-7.69 (m, 11 1). 7.41-7.54 (m, 31 1). 7.26-7.29 (m, 1H), 4.61 (m, 2H), 3.47 (s, 3H), 2.54-2 60 (m, 1H), 2.35-2.42 (m, 31 1). Z-isomer 1H NMR d 8.25-8.28 (m, i l l ). 7.83-7.90 (m, 21 1). 7.38-7.54 (m, 4H), 4.96-5.00 (m, 2H), 3.53-3.56 (m, 31 1 ). 2.62-2.65 (m, 1 1 1). 2.39-2.43 (m, 31 1 ).

Reference： [1]Current Patent Assignee: FMC CORP - WO2019/143757, 2019, A1 Location in patent: Page/Page column 43; 44

67
[ 1035222-37-7 ]
[ 21663-79-6 ]
C₂₃H₁₈N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In methanol at 20℃;

Reference： [1]Current Patent Assignee: GEORGIA INSTITUTE OF TECHNOLOGY - US2019/276454, 2019, A1 Location in patent: Paragraph 0360-0361

68
[ 4509-90-4 ]
[ 21663-79-6 ]
5-bromo-N-(2-propyn-1-yloxy)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;

Reference： [1]Kobori, Yukiko; Okamura, Kohei; Takeda, Norihiko; Ueda, Masafumi; Yasui, Motohiro [Organic Letters, 2020, vol. 22, # 24, p. 9740 - 9744]

69
methyl (E)-3-methoxy-2-(4-oxotetralin-6-yl)prop-2-enoate [ No CAS ]
[ 21663-79-6 ]
methyl (E)-3-methoxy-2-[(4E)-4-prop-2-ynoxyiminotetralin-6-yl]prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol at 20℃; for 2h;	4.3 Step 3: Preparation of methyl (E)-3-methoxy-2-[(4E)-4-prop-2-vnoxyiminotetralin-6-yl]prop-2-enoate To a solution of methyl (E)-3-methoxy-2-(4-oxotetralin-6-yl)prop-2-enoate (61 .0 mg, 0.23 mmol, 1 .00 equiv.) in methanol (1 .20 ml_) was added O-prop-2-ynylhydroxylamine hydrochloride (53.0 mg, 0.47 mmol, 2.00 equiv.). After the suspension was stirred at RT for 2 hours the reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane:EtOAc) to give methyl (E)-3-methoxy-2-[(4E)-4-prop-2-ynoxyiminotetralin-6-yl]prop-2-enoate as a white solid. Melting point: 104-106°C. LC-MS (Method A), Rt = 1 .07 min, MS: (M+H) = 314. 1H NMR (400 MHz, CDCl3) d ppm: 7.95 (d, 1 H), 7.57 (s, 1 H), 7.23 (dd, 1 H), 7.13-7.17 (m, 1 H), 4.80 (d, 2H), 3.87 (s, 3H), 3.75 (s, 3H), 2.77 (m, 4H), 2.49 (t, 1 H), 1 .87 (m, 2H).

Reference： [1]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD; Syngenta (in: Sinochem Holdings) - WO2021/9026, 2021, A1 Location in patent: Page/Page column 56-57

70
methyl (E)-3-methoxy-2-(4-oxoisochroman-6-yl)prop-2-enoate [ No CAS ]
[ 21663-79-6 ]
methyl (E)-3-methoxy-2-[(4Z)-4-prop-2-ynoxyiminoisochroman-6-yl]prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol at 20℃; for 3h;	9 Example 9: Preparation of methyl (E)-3-methoxy-2-[(4Z)-4-prop-2-ynoxyiminoisochroman-6-yl]prop-2- enoate (Compound 1 .42 of Table T1). To a solution of methyl (E)-3-methoxy-2-(4-oxoisochroman-6-yl)prop-2-enoate (100 mg, 0.38 mmol, 1 .00 equiv.) in methanol (0.76 mL) was added O-prop-2-ynylhydroxylamine hydrochloride (90.0 mg, 0.76 mmol, 2.00 equiv.). After, the orange solution was stirred at RT for 3 hours and the reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane :EtOAc) to give methyl (E)-3-methoxy-2-[(4Z)-4-prop-2-ynoxyiminoisochroman-6-yl]prop-2-enoate as a white solid. LC-MS (Method A), Rt = 0.97 min, MS: (M+H) = 316. 1H NMR (400 MHz, CDCl3) d ppm: 7.94 (d, 1 H), 7.59 (s, 1 H), 7.30 (dd, 1 H), 7.1 1 (d, 1 H), 4.79 (d, 2H), 4.78 (s, 2H), 4.68 (s, 2H), 3.88 (s, 3H), 3.76 (s, 3H), 2.50 (t, 1 H).

Reference： [1]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD; Syngenta (in: Sinochem Holdings) - WO2021/9026, 2021, A1 Location in patent: Page/Page column 64

71
[ 960058-93-9 ]
[ 21663-79-6 ]
C₂₄H₂₅N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In water at 20℃; for 6h;	4.3. Synthetic procedure and characterization of prodrug 2 6 (40 mg, 0.1 mmol) and 4 (0.2 mmol) were added to a 25 mL roundbottom flask and partially dissolved in distilled water (1 mL). N-(3- Dimethylaminopropyl)-N′ -ethylcarbodiimide hydrochloride (0.4 mmol) was then added to the mixture in one portion. The pH was monitored and adjusted to 4.5 with a NaOH and / or HCl aqueous solution (1 M). The reaction was stirred for 6 h at rt and constant pH (4.5). Water was removed under reduced pressure, and crude suspended in acetonitrile and vacuum filtered. Solution was purified by semi-preparative TLC eluting with DCM:MeOH/7:3 giving rise a light-yellow solid (12 mg, 27%). 1 H NMR (500 MHz, DMF) δ 11.42 (bs, 1H), 10.69 (s, 1H), 7.54 (d, J = 7.4 Hz, 2H), 7.49 (d, J = 15.9 Hz, 1H), 7.38 (dd, J = 14.0, 7.9 Hz, 3H), 7.21 (dt, J = 8.0, 0.8 Hz, 1H), 6.96 (ddd, J = 8.1, 7.1, 1.2 Hz, 1H), 6.90 (ddd, J = 8.0, 7.1, 1.1 Hz, 1H), 6.44 (d, J = 15.0 Hz, 1H), 4.54 (d, J = 2.4 Hz, 2H), 3.85 (s, 2H), 3.61 (t, J = 2.3 Hz, 1H), 2.83 (m, 2H), 2.72 (m, 2H), 2.30 (s, 3H). 13C NMR (126 MHz, DMSO) δ 162.9, 139.5, 135.2, 133.5, 132.0, 129.0, 128.2 (x2), 127.6 (x2), 119.9, 118.1 (x2), 117.9, 117.3, 110.4, 107.3, 78.9, 78.6, 62.5, 51.7, 48.9, 23.4, 11.2. HRMS (ESI) m/z [M + H]+ calculated for C24H26O2N3, 388.2019; found, 388.2018. UPLC purity: > 95%; Rt: 1.496 min.

Reference： [1]Rubio-Ruiz, Belén; Pérez-López, Ana M.; Sebastián, Víctor; Unciti-Broceta, Asier [Bioorganic and Medicinal Chemistry, 2021, vol. 41]

72
[ 60851-41-4 ]
[ 21663-79-6 ]
C₄₅H₇₁NO₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With sodium methylate In methanol at 20℃; for 12h;

Reference： [1]Duan, Wenfang; Hao, Jie; Hu, Yuhua; Li, Bo; Li, Tianlei; Li, Zhongwen; Lian, Xu; Qin, Tong; Tang, Lei; Wu, Jun; Wu, Song; Zhang, Chi; Zhang, Jihong; Zhang, Wenxuan; Zhao, Xintong [Organic and Biomolecular Chemistry, 2022, vol. 20, # 4, p. 870 - 876]

73
methyl (E)-3-methoxy-2-(3-oxotetralin-5-yl)prop-2-enoate [ No CAS ]
[ 21663-79-6 ]
methyl (E)-3-methoxy-2-[(3E)-prop-2-ynoxyiminotetralin-5-yl]prop-2-enoate [ No CAS ]
methyl (E)-3-methoxy-2-[(3Z)-prop-2-ynoxyiminotetralin-5-yl]prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With anhydrous Sodium acetate In methanol at 20℃; for 0.25h;	2.3 Step 3: Preparation of methyl (E)-3-methoxy-2-(3-prop-2-ynoxyiminotetralin-5-yl)prop-2-enoate To a solution of methyl (E)-3-methoxy-2-(3-oxotetralin-5-yl)prop-2-enoate (100 mg, 0.31 mmol, 1.00 equiv.) in methanol (4.00 mL) was added O-prop-2-ynylhydroxylamine hydrochloride (100 mg, 0.92 mmol, 3.00 equiv.) followed by sodium acetate (76.4 mg, 0.92 mmol, 3.00 equiv.). The resulting reaction mixture was stirred at room temperature for 15 min, diluted with TBME and water, and then extracted with TBME. The total combined organic fraction was washed with water and brine, dried with Na2SO4, filtered, and concentrated under reduced pressure. The resultant crude residue was purified by flash chromatography (cyclohexane:EtOAc) to give methyl (E)-3-methoxy-2-(3-prop-2-ynoxyiminotetralin-5- yl)prop-2-enoate as 2 separate oxime isomers that were isolated as orange oils. (Z)-isomer Compound 1.3 LCMS (Method A), Rt: 0.97 min, M+H: 314,1H NMR (CDCl3) δ: 7.62 (s, 1H), 7.17-7.23 (m, 1H), 7.11-7.15 (m, 1H), 7.04 (m, 1H), 4.68 (d, 2H), 3.86 (s, 3H), 3.73 (s, 3H), 3.60 (s, 2H), 2.92-2.97 (m, 2H), 2.58-2.63 (m, 2H), 2.48 (m, 1H) (E)-isomer Compound 1.4 LCMS (Method A), Rt: 0.99 min, M+H: 314, 1H NMR (CDCl3) δ: 7.61 (s, 1H), 7.15-7.24 (m, 2H), 7.10 (m, 1H), 4.64 (d, 2H), 3.85 (s, 3H), 3.72 (s, 3H), 3.41 (s, 2H), 2.85-2.90 (m, 2H), 2.69-2.74 (m, 2H), 2.45 (m, 1H)
	With anhydrous Sodium acetate In methanol at 20℃; for 0.25h;	2.3 Step 3: Preparation of methyl (E)-3-methoxy-2-(3-prop-2-ynoxyiminotetralin-5-yl)prop-2-enoate To a solution of methyl (E)-3-methoxy-2-(3-oxotetralin-5-yl)prop-2-enoate (100 mg, 0.31 mmol, 1.00 equiv.) in methanol (4.00 mL) was added O-prop-2-ynylhydroxylamine hydrochloride (100 mg, 0.92 mmol, 3.00 equiv.) followed by sodium acetate (76.4 mg, 0.92 mmol, 3.00 equiv.). The resulting reaction mixture was stirred at room temperature for 15 min, diluted with TBME and water, and then extracted with TBME. The total combined organic fraction was washed with water and brine, dried with Na2SO4, filtered, and concentrated under reduced pressure. The resultant crude residue was purified by flash chromatography (cyclohexane:EtOAc) to give methyl (E)-3-methoxy-2-(3-prop-2-ynoxyiminotetralin-5- yl)prop-2-enoate as 2 separate oxime isomers that were isolated as orange oils. (Z)-isomer Compound 1.3 LCMS (Method A), Rt: 0.97 min, M+H: 314,1H NMR (CDCl3) δ: 7.62 (s, 1H), 7.17-7.23 (m, 1H), 7.11-7.15 (m, 1H), 7.04 (m, 1H), 4.68 (d, 2H), 3.86 (s, 3H), 3.73 (s, 3H), 3.60 (s, 2H), 2.92-2.97 (m, 2H), 2.58-2.63 (m, 2H), 2.48 (m, 1H) (E)-isomer Compound 1.4 LCMS (Method A), Rt: 0.99 min, M+H: 314, 1H NMR (CDCl3) δ: 7.61 (s, 1H), 7.15-7.24 (m, 2H), 7.10 (m, 1H), 4.64 (d, 2H), 3.85 (s, 3H), 3.72 (s, 3H), 3.41 (s, 2H), 2.85-2.90 (m, 2H), 2.69-2.74 (m, 2H), 2.45 (m, 1H)

Reference： [1]Current Patent Assignee: Syngenta (in: Sinochem Holdings); SINOCHEM HOLDINGS CORPORATION LTD - WO2022/58580, 2022, A1 Location in patent: Page/Page column 57-58
[2]Current Patent Assignee: Syngenta (in: Sinochem Holdings); SINOCHEM HOLDINGS CORPORATION LTD - WO2022/58580, 2022, A1 Location in patent: Page/Page column 57-58

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	21663-79-6	MDL No. :	MFCD12912207
Formula :	C₃H₆ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CEFBXYRCGUITCZ-UHFFFAOYSA-N
M.W :	107.54	Pubchem ID :	13502403
Synonyms :

Num. heavy atoms :	6
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.33
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	25.45
TPSA :	35.25 Å²

GI absorption :	High
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) :	-6.78 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.25
Log Po/w (WLOGP) :	0.39
Log Po/w (MLOGP) :	0.49
Log Po/w (SILICOS-IT) :	-0.64
Consensus Log Po/w :	0.1

[ CAS No. 21663-79-6 ] {[proInfo.proName]}

Quality Control of [ 21663-79-6 ]

Related Doc. of [ 21663-79-6 ]

Product Details of [ 21663-79-6 ]

Calculated chemistry of [ 21663-79-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 21663-79-6 ]

Application In Synthesis of [ 21663-79-6 ]

[ 21663-79-6 ] Synthesis Path-Downstream 1~73

Related Functional Groups of
[ 21663-79-6 ]

Alkynes

Aliphatic Chain Hydrocarbons

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-0.6
Solubility :	27.1 mg/ml ; 0.252 mol/l
Class :	Very soluble
Log S (Ali) :	-0.55
Solubility :	30.2 mg/ml ; 0.281 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	0.39
Solubility :	266.0 mg/ml ; 2.47 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.97

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
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. 21663-79-6 ] {[proInfo.proName]}

Quality Control of [ 21663-79-6 ]

Related Doc. of [ 21663-79-6 ]

Product Details of [ 21663-79-6 ]

Calculated chemistry of [ 21663-79-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 21663-79-6 ]

Application In Synthesis of [ 21663-79-6 ]

[ 21663-79-6 ] Synthesis Path-Downstream 1~73

Related Functional Groups of [ 21663-79-6 ]

Alkynes

Aliphatic Chain Hydrocarbons

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

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[ 21663-79-6 ]