Name: 159634-94-3|(R)-2-(2-((tert-Butoxycarbonyl)amino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acid|97%
Brand: Ambeed
SKU: A740275
Rating: 94 (32 reviews)

1
[ 4735-50-6 ]
[ 159634-94-3 ]
{1-[(R)-2-(1H-Indol-3-yl)-1-(2-naphthalen-1-yl-ethylcarbamoyl)-ethylcarbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In dichloromethane

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

2
[ 2018-90-8 ]
[ 159634-94-3 ]
(1-{(R)-2-(1H-Indol-3-yl)-1-[(naphthalen-2-ylmethyl)-carbamoyl]-ethylcarbamoyl}-1-methyl-ethyl)-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In dichloromethane

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

3
[ 13214-66-9 ]
[ 159634-94-3 ]
{1-[(R)-2-(1H-Indol-3-yl)-1-(4-phenyl-butylcarbamoyl)-ethylcarbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In dichloromethane

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

4
[ 2038-57-5 ]
[ 159634-94-3 ]
{1-[(R)-2-(1H-Indol-3-yl)-1-(3-phenyl-propylcarbamoyl)-ethylcarbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In dichloromethane

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

5
[ 118-31-0 ]
[ 159634-94-3 ]
(1-{(R)-2-(1H-Indol-3-yl)-1-[(naphthalen-1-ylmethyl)-carbamoyl]-ethylcarbamoyl}-1-methyl-ethyl)-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In dichloromethane

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

6
[ 64-04-0 ]
[ 159634-94-3 ]
{1-[(R)-2-(1H-Indol-3-yl)-1-phenethylcarbamoyl-ethylcarbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In dichloromethane

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

7
[ 159634-93-2 ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen In ethanol
	With hydrogen

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]
[2]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

8
[ 39512-51-1 ]
[ 159634-94-3 ]
{1-[(R)-1-(1H-Indol-3-ylmethyl)-2-oxo-2-(4-o-tolyl-piperazin-1-yl)-ethylcarbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

9
[ 39512-50-0 ]
[ 159634-94-3 ]
{1-[(R)-2-[4-(2-Chloro-phenyl)-piperazin-1-yl]-1-(1H-indol-3-ylmethyl)-2-oxo-ethylcarbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

10
[ 35386-24-4 ]
[ 159634-94-3 ]
(1-{(R)-1-(1H-Indol-3-ylmethyl)-2-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethylcarbamoyl}-1-methyl-ethyl)-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

11
[ 119695-82-8 ]
[ 159634-94-3 ]
(1-{(R)-1-(1H-Indol-3-ylmethyl)-2-[4-(2-isopropyl-phenyl)-piperazin-1-yl]-2-oxo-ethylcarbamoyl}-1-methyl-ethyl)-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

12
[ 5241-64-5 ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: EDC, DMAP / CH₂Cl₂ / 0 °C 2: HCl / ethyl acetate / 0 °C 3: HOBt, EDC / Ambient temperature 4: H₂ / Pd/C

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

13
[ 141595-98-4 ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: HOBt, EDC / Ambient temperature 2: H₂ / Pd/C
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]
[2]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

14
[ 126090-33-3 ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: HCl / ethyl acetate / 0 °C 2: HOBt, EDC / Ambient temperature 3: H₂ / Pd/C

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

15
[ 159634-94-3 ]
2-Amino-N-[(R)-1-(1H-indol-3-ylmethyl)-2-oxo-2-(4-o-tolyl-piperazin-1-yl)-ethyl]-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: HOBt, EDC / CH₂Cl₂ 2: HCl / ethyl acetate / 0 °C

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

16
[ 159634-94-3 ]
2-Amino-N-[(R)-2-[4-(2-chloro-phenyl)-piperazin-1-yl]-1-(1H-indol-3-ylmethyl)-2-oxo-ethyl]-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: HOBt, EDC / CH₂Cl₂ 2: HCl / ethyl acetate / 0 °C

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

17
[ 159634-94-3 ]
2-Amino-N-{(R)-1-(1H-indol-3-ylmethyl)-2-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: HOBt, EDC / CH₂Cl₂ 2: HCl / ethyl acetate / 0 °C

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

18
[ 159634-94-3 ]
2-Amino-N-{(R)-1-(1H-indol-3-ylmethyl)-2-[4-(2-isopropyl-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: HOBt, EDC / CH₂Cl₂ 2: HCl / ethyl acetate / 0 °C

Reference： [1]Barakat, Khaled J.; Cheng, Kang; Chan, Wanda W.-S; Butler, Bridget S.; Jacks, Thomas M.; Schleim, Klaus D.; Hora Jr., Donald F.; Hickey, Gerard J.; Smith, Roy G.; Patchett, Arthur A.; Nargund, Ravi P. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 11, p. 1431 - 1436]

19
[ 30992-29-1 ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr
	Multi-step reaction with 2 steps 1: triethylamine; 3-hydroxy-3,4-dihydrobenzotriazine-4-one; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 3 h / 38 °C / Inert atmosphere; Large scale 2: sodium hydroxide / water; tert-butyl methyl ether / 20 °C / Large scale

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]
[2]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

20
[ 159634-94-3 ]
2-Amino-N-[(R)-2-(1H-indol-3-yl)-1-phenethylcarbamoyl-ethyl]-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

21
[ 159634-94-3 ]
2-Amino-N-[(R)-2-(1H-indol-3-yl)-1-(3-phenyl-propylcarbamoyl)-ethyl]-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

22
[ 159634-94-3 ]
2-Amino-N-[(R)-2-(1H-indol-3-yl)-1-(4-phenyl-butylcarbamoyl)-ethyl]-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

23
[ 159634-94-3 ]
2-Amino-N-{(R)-2-(1H-indol-3-yl)-1-[(naphthalen-2-ylmethyl)-carbamoyl]-ethyl}-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

24
[ 159634-94-3 ]
2-Amino-N-{(R)-2-(1H-indol-3-yl)-1-[(naphthalen-1-ylmethyl)-carbamoyl]-ethyl}-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

25
[ 159634-94-3 ]
2-Amino-N-[(R)-2-(1H-indol-3-yl)-1-(2-naphthalen-1-yl-ethylcarbamoyl)-ethyl]-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: EDC, HOBt, DIEA / CH₂Cl₂ 2: H₂ / Pd/C / ethanol / 760 Torr

Reference： [1]Yang, Lihu; Morriello, Greg; Pan, Yanping; Nargund, Ravi P.; Barakat, Khaled; Prendergast, Kristine; Cheng, Kang; Chan, Wanda W.-S.; Smith, Roy G.; Patchett, Arthur A. [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 7, p. 759 - 764]

26
C₁₇H₁₇N₃O₂ [ No CAS ]
[ 159634-94-3 ]
[ 220541-26-4 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 16h;	1.1T.R4 A mixture of ethyl 2-(2-naphthyl)-2-(4-nitroimidazolyl) acetate (2.04 grams, 6.27 mmol), tetrahydrofuran (20 mL), and 10% palladium on carbon (2.04 gram) was hydrogenated at ambient temperature and pressure until complete as determined by hplc (20 hours). The catalyst was removed by filtration and rinsed with tetrahydrofuran (10 mL). The filtrate was added to a slurry consisting of 1-[3-(dimethyl amino)propyl-3-ethylcarbodiimide hydrochloride (1.20 grams, 6.27 mmol), tetrahydrofuran (10 mL), and (2R)-2-{2-[(tert-butoxy)carbonylamino]-2-methylpropanoylamino}-3-indol-3-ylpropanoic acid (2.44 grams, 6.27 mmol) and stirred 16 hours at ambient temperature. The reaction mixture was partitioned between water (150 mL) and ethyl acetate (3×50 mL). The organic extracts were combined, washed with saturated sodium chloride solution, dried using sodium sulfate, and evaporated. The resulting crude oil was purified by column chromatography on silica gel with hexane ethyl acetate: methanol (10:10:1) as an eluent giving 1.72 grams (41%) of ethyl 2-[4-((2R)-2-{2-[(tert-butoxy) carbonylamino]-2-methylpropanoylamino}-3-indol-3-ylpropanoyl amino)imidazolyl]-2-(2-naphthyl)acetate. A 0.2 gram sample was further purified using preparative reverse phase hplc to give 0.16 grams of ethyl 2-[4-{(2R)-2-{2-[(tert-butoxy) carbonylamino]-2-methylpropanoylamino}-3-indol-3-ylpropanoyl amino)imidazolyl]-2-(2-naphthyl)acetate for analytical study. MS (FIA) m/z 667.4 [(M+H)+]. Anal. calcd. exact mass for C37H43N6O6 [((M+H)+]=667.3244. Exact mass found by mass spectrometry: C37H43N6O6 [(M+H)+]=667.3254. 1H nmr (CDCl3): 1.25-1.42 (m, 19H), 3.24-3.33 (m, 2H), 4.28-4.33 (m, 2H), 4.98-5.01 (m, 1H), 5.94 (s, 1H), 6.85-7.01 (m, 3H), 7.18-7.21 (m, 2H), 7.35-7.39 (m, 2H), 7.49-7.58 (m, 4H), 7.78-7.84 (m, 4H), 8.69 (s, 1H), 10.65 (s, broad, 1H).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 48

27
C₁₆H₂₀N₄O₂ [ No CAS ]
[ 159634-94-3 ]
[ 220530-33-6 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In tetrahydrofuran at 20℃;	2-43.15 The product of Preparation EX9A (0.85 g, 2.57 mmol) was combined with 10% palladium/carbon (0.50 g) and palladium/black (0.15 g) in tetrahydrofuran (40 mL)and the mixture shaken under a hydrogen atmosphere (38 psi) in a Parr apparatus. After reduction was complete, the catalyst was removed by filtration through celite and the amine/tetrahydrofuran solution was immediately combined with 1,3-dicyclohexylcarbodiimide (0.53 g, 2.57mmol), 1-hydroxybenzotriazole (0.35 g, 2.57 mmol), the product of Preparation 1L (1.00 g, 2.57 mmol) and additional tetrahydrofuran (60 mL) After stirring overnight at ambient temperature, the mixture was concentrated and the residue slurried in ethyl acetate and filtered. The filtrate was concentrated and the residue purified by flash chromatography(silica gel, chloroform/methanol) which gave 1.62 g of the desired product which was used without further purification.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 117

28
C₁₉H₁₉N₃O₂ [ No CAS ]
[ 159634-94-3 ]
[ 220534-00-9 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 16h;	2-46.345 To a mixture of the product of Preparation 11 (6.0 g, 17.1 mmol) and 10% palladium on carbon (6.0 g) in tetrahydrofuran (100 mL). The reaction mixture was placed under a hydrogen atmosphere (40 psi) using a Parr apparatus for 30 min then filtered through Celite. The resulting solution was then added to a previously prepared mixture of the product of Preparation 1L (6.66 g, 17.1 mmol), 1-hydroxybenzotriazole (2.31 g, 17.1 mmol), and 1,3 dicyclohexylcarbodiimide (3.53 g, 17.1 mmol) in tetrahydrofuran (75 mL). After 16 h at room temperature, the reaction mixture was concentrated and the crude material purified by flash chromatography (silica gel, 4% methanol/dichloromethane) to yield 6.17 g (52%) of the desired product as a brown foam: 1H NMR consistent with structure; MS (ion spray) 693 (M+1).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 122

29
C₁₄H₁₈N₄O₂ [ No CAS ]
[ 159634-94-3 ]
[ 220530-51-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;	2-44.19 The compound of preparation 17 (0.73 g, 2.38 mmol) was combined with 10% palladium/carbon (0.50 g) and palladium/black (0.10 g) in tetradyrofuran(40 mL)and the mixture shaken under hydrogen (38 psi) in a Parr apparatus. After reduction was complete, the catalyst was removed by filtration through celite and the resulting solution was immediately combined with dicyclohexylcarbodiimide (0.49 g, 2.38 mmol), 1-hydroxybenzotriazole mono-hydrate (0.32 g, 2.37 mmol), the product of Preparation 1L (0.93 g, 2.39 mmol) and additional tetrahydrofuran (60 mL). After stirring overnight at ambient temperature, the mixture was concentrated and the residue slurried in ethyl acetate and filtered. The filtrate was concentrated and the residue purified by silica gel chromatography (chloroform/methanol) to provide 0.76 g (50%) of the desired product as an off white solid which was used without further purification.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 119

Yield	Reaction Conditions	Operation in experiment
		2.C C. C. (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid To a solution of 1.03 g (2.64 mmol) of 2B in 10 mL of THF was added 381 mg (9.1 mmol) of lithium hydroxide hydrate in 2 mL of water and the mixture was stirred overnight at room temperature. Excess THF was removed by evaporation, and the basic aqueous mixture was extracted three times with ethyl acetate, and then acidified to pH 4 with dilute acetic or hydrochloric acid. The product was extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over MgSO4 and evaporated to give 1.03 g of 2C as an orange foam. MS (Cl, NH3) 390 (MH+). 1H NMR (CDCl3 300 MHz) δ7.61 (d, 1H), 7.48 (d, 1H), 7.27 (t, 1H), 7.10 (t, 1H), 4.81 (bs, 1H), 3.35 (m, 1H), 1.49 (s, 6H), 1.32 (s, 9H).
		4.C C. C. (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid The product from 4B was hydrolyzed according to the method described in General Procedure D to give 1.03 g of 4C as an orange foam. 1 H NMR (CDCl3 300 MHz) δ 7.61 (d, 1H), 7.48 (d,1H), 7.27 (t,1H), 7.10 (t, 1H), 4.81 (bs, 1H), 3.35 (m, 1H), 1.49 (s, 6H), 1.32 (s, 9H). MS (Cl, NH3) 390 (MH+)
		2.C C. C. (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1 H-indol-3-yl)-propionic acid To a solution of 1.03 g (2.64 mmol) of 2 B in 10 mL of THF was added 381 mg (9.1 mmol) of lithium hydroxide hydrate in 2 mL of water and the mixture was stirred overnight at room temperature. Excess THF was removed by evaporation, and the basic aqueous mixture was extracted three times with ethyl acetate, and then acidified to pH 4 with dilute acetic or hydrochloric acid. The product was extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over MgSO4 and evaporated to give 1.03 g of 2 C as an orange foam. MS (Cl, NH3) 390 (MH+). 1 H NMR (CDCl3 300 MHz)δ 7.61 (d, 1 H), 7.48 (d, 1 H), 7.27 (t, 1 H), 7.10 (t, 1 H), 4.81 (bs, 1 H), 3.35 (m, 1 H), 1.49 (s, 6 H), 1.32 (s, 9 H).

		16.C C. C. (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid To a stirring solution of 30.6 g (0.15 mol) of D-trypotophan, 30.4 g (0.30 mol) of N-methylmorpholine in 450 mL of (4:1) dioxane:water, was added 45.0 g (0.15 mol) of 14E and the mixture was stirred for about 72 h. Excess dioxane was removed by evaporation and water and ethyl acetate were added to the mixture. The pH of the solution was adjusted to 3 with concentrated HCl and the layers were separated. The organic layer was washed with water and brine, dried over MgSO4 and concentrated. The residue was crystallized from ethyl acetate/hexanes to give 37.0 g of an off-white solid.
102%		6.D Step D Step D (R)-α-[(2-t-Butoxycarbonylamino-2-methyl-1-oxopropyl)amino]-1H-indole-3-propanoic acid The benzyl ester (0.82 g, 1.71 mmol) obtained in Step C and 10% palladium on carbon (150 mg) were stirred together in ethyl acetate (5 mL). The solution was degassed and a hydrogen atmosphere introduced over the reactants using a balloon for 32 hours. The reaction products were isolated by filtering the reaction mixture through a Celite plug. The plug was washed with additional ethyl acetate (3*10 mL). The combined filtrates were evaporated under vacuum to afford the product (680 mg, 102%). 1 H NMR (400 MHz, CDCl3): 1.30 (s, 9H), 1.41 (s, 6H), 3.32 (dd, 1H), 3.42 (m, 1H), 4.87 (br s, 1H), 6.82 (d, 1H), 7.13-7.35 (m, 8H), 7.60 (d, 1H), 8.28 (br s, 1H).

31
[ 153-94-6 ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine In 1,4-dioxane; water; ethyl acetate	16.C C. C. (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid To a stirring solution of 30.6 g (0.15 mol) of D-tryptophan, 30.4 g (0.30 mol) of N-methylmorpholine in 450 mL of (4:1) dioxane:water, was added 45.0 g (0.15 mol) of 14E and the mixture was stirred for about 72 h. Excess dioxane was removed by evaporation and water and ethyl acetate were added to the mixture. The pH of the solution was adjusted to 3 with concentrated HCl and the layers were separated. The organic layer was washed with water and brine, dried over MgSO4 and concentrated. The residue was crystallized from ethyl acetate/hexanes to give 37.0 g of an off-white solid.

Reference： [1]Current Patent Assignee: PFIZER INC - US6448263, 2002, B1

32
[ 159634-94-3 ]
N-[1(R)-[(3,4-dihydro-6-methanesulfonylamino-4-oxo-spiro[2H-1-benzopyran-2,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-amino-2-methylpropanamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		13 N-[1(R)-[(3,4-dihydro-6-methanesulfonylamino-4-oxo-spiro[2H-1-benzopyran-2,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-amino-2-methylpropanamide hydrochloride EXAMPLE 13 N-[1(R)-[(3,4-dihydro-6-methanesulfonylamino-4-oxo-spiro[2H-1-benzopyran-2,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-amino-2-methylpropanamide hydrochloride The title compound was prepared from α(R)-[[2-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid and 3,4-dihydro-6-methanesulfonylamino-4-oxo-spiro[2H-1-benzopyran-2,4'-piperidine]following procedures described in Example 10, Steps A and B.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5536716, 1996, A

33
[ 159634-94-3 ]
[ 185525-55-7 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1,2-dichloro-ethane	17.C N-[1(R)-[(spiro[9H-fluorene-9,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-[[(1,1-dimethylethyloxy)carbonyl]amino]-2-methylpropanamide Step C N-[1(R)-[(spiro[9H-fluorene-9,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-[[(1,1-dimethylethyloxy)carbonyl]amino]-2-methylpropanamide The title compound was prepared by the procedure described in Example 15, Step D using the intermediate from the previous step (275 mg, 1.162 mmol), α(R)-[[2-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid (453 mg, 1.16 mmol), HOBT (156 mg, 1.16 mmol), and EDC (223 mg, 1.16 mmol). Reaction time: 30 minutes. Yield: 371 mg (53%). 1 H NMR (400 MHz, CDCl3): δ8.225 (br. s, 1H), 7.698-7.159 (m, 13H), 6.610 (d, 1H), 5.348-5.265 (m, 1H), 5.020 (br. s, 1H), 3.988-3.905 (m, 1H), 3.595-3.502 (m, 2H) 3.365-3.296 (m, 1H), 3.189 (t, 1H), 1.718-1.655 (m, 1H), 1.545, 1.518, (2s, 6H), 1.611-1.281 (m, 3H), 1.467 (s, 9H), 0.932-0.865 (m, 1H). FAB-MS calc. for C37 H42 N4 O4 606; found 607 (M+H, 23%).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5578593, 1996, A

34
[ 109-02-4 ]
[ 159634-94-3 ]
[ 180465-59-2 ]

Yield	Reaction Conditions	Operation in experiment
21 mg (81%)	With benzotriazol-1-ol; 1,2-dichloro-ethane	5.A Step A Step A N-[1(R)-[(3-hydrospiro[1H-isobenzofuran-1,4'-piperidin]-1'-yl)-carbonyl]-2-(indol-3-yl)ethyl]-2-[[(1,1-dimethyl -ethyloxy)carbonyl]amino]-2-methylpropanamide Prepared by the procedure described in Example 3, Step B. 3-Hydrospiro[1H-isobenzofuran-1,4'-piperidine]hydrochloride (10 mg, 0.044 mmol), (Bauer et al U.S. Pat. No. 3,985,889) α(R)-[[2-[[(1,1-dimethyl-ethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid (20 mg, 0.051 mmol), HOBT (1 eq.), N-methyl-morpholine (0.01 mL, 0.093 mmol), and EDC (20 mg, 0.10 mmol). Reaction time: 5 hours. Yield: 21 mg (81%). The product exists as a mixture of two conformers (1:1): (1 H NMR CDCl3): δ5 8.096 (s, 1 H), 7.689 (t, 1 H), 7.341 (d, 1 H), 7.244-6.611 (m, 6 H), 5.288-5.202 (m, 1/2H), 4.945 (br. s, 1/2H), 4.161 (d, 1/2H), 4.003 (d, 1/2H), 3.338 (d, 1/2H), 3.280-3.115 (m, 2 H), 3.005-2.861 (m, 1 H), 2.751 (d, 1/2H), 2.416 (d, 1/2H), 1.787-1.549 (m 3 1/2H), 1.491, 1.461, 1.421, 1.410 (4s, 12 H), 1.281-1.212 (m, 3 H), 0.857 (t, 6 H). FAB-MS calc. for C32 H40 N4 O5 560; found 561 (M+H, 33%).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5536716, 1996, A

35
[ 109-02-4 ]
[ 159634-94-3 ]
[ 159634-69-2 ]

Yield	Reaction Conditions	Operation in experiment
34 mg (86%)	With benzotriazol-1-ol; 1,2-dichloro-ethane	6.A Step A Step A N-[1(R)-[(3,4-dihydro-6-methyl-4-oxospiro[2H-1-benzopyran-2,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-[[(1,1 -dimethylethyloxy)carbonyl]amino]-2-methylpropanamide Prepared by the procedure described in Example 3, Step B. 3,4-Dihydro-6-methylspiro[2H- 1 -benzopyran-2,4'-piperidine]-4-one hydrochloride (20 mg, 0.058 mmol), (Hashigaki et al Chem. Pharm. Bull. 32 pg 3561-3568 (1984)) α(R)-[[2-[[(1,1-dimethylethoxy)-carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3propanoic acid) (32 mg, 0.082 mmol), HOBT (1 eq.), N-methyl morpholine (0.03 mL, 0.28 mmol), and EDC (40 mg, 0.21 mmol). Reaction time: 8 hours. Yield: 34 mg (86%). 1 H NMR (400 MHz, CDCl3): The product exists as a mixture of two conformers (2:1): δ8.154 (s, 2/3H), 8.088 (s, 1/3H), 7.626 (d, 2/3H), 7.591-7.060 (m, 6 H), 6.725-6.688 (m, 2/3H), 5.265-5.168 (m, 2/3H), 4.985-4.900 (m, 2/3H), 4.289-4.178 (m, 2/3H), 3.469 (s, 2/3H), 3.229-3.064 (m, 2 2/3H), 2.730 (t, 2/3H), 2.562 (s, 2 1/3H), 2.251 (d, 2 1/3H), 2.158 (d, 2/3H), 2.068 (d, 2/3H), 1.680-1.541 (m, 3 H), 1.502, 1.475, 1.454, 1.427, 1.402 (5s, 15 H), 1.292-1.226 (m, 3 H), 0.616-0.532 (m, 1/3H), -0.495 -0.590 (m, 1/3H). FAB-MS calc. for C34 H42 N4 O6 602; found 603. (M+H, 37%).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5536716, 1996, A

36
[ 109-02-4 ]
[ 159634-94-3 ]
N-[1(R)-[(1,4-dihydro-4-phenyl-1-oxospiro[3H-2-benzopyran-3,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-[[(1,1-dimethylethyloxy)carbonyl]amino]-2-methylpropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9.2 mg (86%)	With benzotriazol-1-ol; 1,2-dichloro-ethane	10.B Step B Step B N-[1(R)-[(1,4-dihydro-4-phenyl-1-oxospiro[3H-2-benzopyran-3,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-[[(1,1-dimethylethyloxy)carbonyl]amino]-2-methylpropanamide Prepared by the procedure described in Example 3, Step B. The intermediate from previous Step (5 mg, 0.017 mmol), α(R)-[[2-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid (12 mg, 0.030 mmol), HOBT (1 eq.), N-methyl morpholine (1 eq.), and EDC (12 mg, 0.060 mmol). Reaction time: 5 hours. Yield: 9.2 mg (86%). 1 H NMR(400 MHz, CD3 OD): The product exists as a mixture of two conformers (1:1): δ8.185-8.072 (m, 1 1/2H), 7.885 (s, 1/2H), 7.710- 6.813 (m; 12 H), 5.331-5.309 (m; 1/2H), 5.198-5.111 (m, 1/2H), 4.710-4.605 (m, 1/2H), 4.300-4.235 (m, 1/2H), 3.876 (d, 1/2H), 3.719-3.617 (m, 1 H), 3.355-3.046 (m; 1 1/2H) 2.746 (q, 1/2H), 2.006-1.960 (m, 1 H), 1.678-1.574 (m, 2 H), 1.438, -1.368 (m, 6 H), 1.257, 1.240, 1.227, 1.208, 1.186 (5s, 5 H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5536716, 1996, A

37
(2R)-[[-2-[[1,1-dimethylethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid [ No CAS ]
[ 137730-67-7 ]
[ 159634-94-3 ]
[ 185525-56-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With 4-methyl-morpholine; hydrogenchloride; benzotriazol-1-ol; 1,2-dichloro-ethane; In hexane; dichloromethane; ethyl acetate;	Step A N-[1(R)-[(spiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl]-2-[[(1,1-dimethylethyloxy)carbonyl]amino ]-2-methylpropanamide To a stirred solution of alpha(R)-[[2-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid (50 mg, 0.13 mmol), (Example 4, Step D) spiro[1H-indene-1,4'-piperidine]hydrochloride (28.5 mg, 0.13 mmol) (Chambers, M. et al, J. Med. Chem. 1992, 35, 2033-2039), HOBT (17.3 mg, 0.13 mmol) and N-methylmorpholine (14.1 muL, 0.13 mmol) in dichloromethane (5 mL) at room temperature was added EDC (49.3 mg, 0.26 mmol). The reaction mixture was stirred for four hours and poured into a mixture of brine (10 mL) and HCl (3N, 1 mL). The mixture was extracted with ethyl acetate (20 mL) and the organic extract was dried (MgSO4) and evaporated. The residue was purified by silica gel column eluding with a solvent gradient of 40-60% ethyl acetate in hexane to give the product (63.6 mg, 89%). 1 H NMR (400 MHz, CDCl3): compound exists as a mixture of conformers (ratio 2:1): delta8.28, 8.24 (2 br. s, 1H), 7.74, 7.62 (2d, 7.7 Hz, 1H), 7.62, 7.39 (2d, 8.0 Hz, 1H), 7.30-7.10 (m, 7H), 6.68-6.30 (m, 2H), 5.35-5.20 (2m, 1H), 5.00 (br. s, 1H), 4.45-4.36 (m, 1H), 3.62, 3.53 (br. d, 14 Hz, 1H), 3.30-3.00 (m, 2H), 2.86-2.71 (m, 1H), 2.42-2.23 (m, 1/3H), 1.71 (v. br. s, 2H), 1.51, 1.49, 1.47 (3s, 6H), 1.44, 1.43, (2s, 9H), 1.40-1.07 (m, 2H), 0.88, 0.72 (2 br. d, 1H), 0.42 (dt, 4 Hz, 12 Hz, 1/3H).

Reference： [1]Patent: US5578593,1996,A

38
[ 159634-94-3 ]
[ 159635-27-5 ]
[ 159635-30-0 ]

Yield	Reaction Conditions	Operation in experiment
		51.E Step E Step E N-[1(R)-[(2-Methylspiro[isoindolin-1-one-3,4'-piperidin]-1'-yl)carbonyl]-2-(indol-3-yl)ethyl ]-2-[[(1,1-dimethylethyloxy)carbonyl]amino]-2-methylpropanamide The compound was prepared according to standard peptide coupling technology from α(R)-[[2-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid (25 mg) and the product from Step B 1 H NMR (400 MHz, CDCl3): δ8.58, 8.44 (2 br. s, 1H), 7.80-7.15, 6.44 (m, d, J=7.6Hz, total 10H), 5.43-5.36, 5.22-5.15, (2m, 1H), 4.98 (br. s, 1H), 4.60-4.50 (br. m, 1H), 3.64-3.50 (br. m, 1H), 3.40-3.05, 2.72-2.64, (2m, 4H), 2.88, 2.51 (2s, 3H), 2.00-1.90 (m, 2H), 1.52, 1.51 (2s, 3H), 1.49 (s, 3H), 1.45, 1.44 (2s, 9H), 1.40-0.40 (several m, 2H). FAB-MS calc. for C33 H41 N5 O5, 587; found 588 (M+H), 532, 488.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5536716, 1996, A

39
[ 159634-94-3 ]
Ethyl 2-[4-((2R)-2-{2-[(Tert-butoxy)carbonylamino]-2-methyl propanoylamino}-3-indol-3-ylpropanoylamino)imidazolyl]-2-phenylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	In methanol; dichloromethane	4 Ethyl 2-[4-((2R)-2-{2-[(Tert-butoxy)carbonylamino]-2-methyl propanoylamino}-3-indol-3-ylpropanoylamino)imidazolyl]-2-phenylacetate Preparation 4 Ethyl 2-[4-((2R)-2-{2-[(Tert-butoxy)carbonylamino]-2-methyl propanoylamino}-3-indol-3-ylpropanoylamino)imidazolyl]-2-phenylacetate This compound was obtained from the reduction of ethyl 2-(4-nitroimidazolyl)-2-phenylacetate and subsequent reaction with (2R)-2-{2-[(tert-butoxy)carbonylamino]-2-methyl propanoylamino}-3-indole-3-ylpropanoic acid as a yellow foam in 73% yield after purification by flash chromatography using dichloromethane:methanol (19:1) as the eluent. MS (FIA) m/z 617.5 [(M+H)+]. 1H nmr (CDCl3): δ1.19-1.32 (m, 18H), 3.10-3.12 (m, 1H), 3.16-3.17 (m, 1H), 3.32 (s, 1H), 4.22-4.27 (m, 2H), 4.69 (s, broad, 1H), 6.44 (s, 1H), 6.85-6.91 (m, 2H), 7.00 (t, 1H), 7.07-7.08 (m, 1H), 7.38-7.40 (m, 1H), 7.42-7.45 (m, 6H), 7.55-7.56 (m, 2H), 10.16 (s, broad, 1H), 10.75 (s, 1H).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6329342, 2001, B1

40
[ 109-02-4 ]
[ 3140-73-6 ]
2-(4-aminoimidazolyl)-2-phenyl-1-pyrrolidinylethan-1-one, hydrochloride [ No CAS ]
[ 159634-94-3 ]
[ 220540-73-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	In water	1 N-((1R)-2-indol-3-yl-1-{N-[1-(2-oxo-1-phenyl-2-pyrrolidinylethyl)imidazol-4-yl]carbamoyl}ethyl)-2-[(tert-butoxy)carbonylamino]-2-methylpropanamide Example 1 N-((1R)-2-indol-3-yl-1-{N-[1-(2-oxo-1-phenyl-2-pyrrolidinylethyl)imidazol-4-yl]carbamoyl}ethyl)-2-[(tert-butoxy)carbonylamino]-2-methylpropanamide N-Methyl morpholine (0.28 mL, 8.32 mm, 1 eq) was added to a stirred slurry of 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.46 g, 2.57 mm, 1 eq) and (2R)-2-{2-[(tert-butoxy)carbonylamino]-2-methylpropanoylamino}-3-indol-3-ylpropanoic acid (1 g, 2.57 mm) in 10 mL of anhydrous tetrahydrofuran cooled to less than 0° C. After 1.5 hours, 2-(4-aminoimidazolyl)-2-phenyl-1-pyrrolidinylethan-1-one, hydrochloride (0.97 g, 2.82 mm, 1.1 eq) was added and stirring was continued at ice bath temperatures. The reaction was stirred for 4 hours and quenched by the addition of 15 mL of deionized water and ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution, dried over magnesium sulfate and the volatiles were removed under vacuum to give the crude product as a light purple foam (1.4 g, 84%) The crude product was purified by preparative chromatography to provide 0.52 g (31.5%) of the product as a foam. 1H nmr (CDCl3): δ1.10-1.40 (m, 15H), 1.67-1.92 (m, 3H), 2.92-3.60 (m, % H), 4.90 (s, broad, 1H), 5.33 (s, broad, 1H), 5.85 (d, 1H), 6.80-7.05 (m, 3H), 7.13-7.39 (m, 10H), 7.44-7.80 (m, 2H), 8.96 (s, broad, 1H), 10.20 (s, broad, 1H).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6329342, 2001, B1

41
[ 220535-75-1 ]
[ 159634-94-3 ]
[ 220541-31-1 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 2-(4-nitroimidazolyl)-2-phenylacetic acid Stage #2: (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid	1.1T.R5 This compound was obtained from the reduction of ethyl 2-(4-nitroimidazolyl)-2-phenylacetate and subsequent reaction with (2R)-2-{2-[(tert-butoxy) carbonylaminol]-2-methyl propanoylamino}-3-indole-3-ylpropanoic acid as a yellow foam in 73% yield after purification by flash chromatography using dichloromethane: methanol (19:1) as the eluent. MS (FIA) m/z 617.5 [(M+H)+]. 1H nmr (CDCl3): δ 1.19-1.32 (m, 18H), 3.10-3.12 (m, 1H), 3.16-3.17 (m, 1H), 3.32 (s, 1H), 4.22-4.27 (m, 2H), 4.69 (s, broad, 1H), 6.44 (s, 1H), 6.85-6.91 (m, 2H), 7.00 (t, 1H), 7.07-7.08 (m, 1H), 7.38-7.40 (m, 1H), 7.42-7.45 (m, 6H), 7.55-7.56 (m, 2H), 10.16 (s, broad, 1H), 10.75 (s, 1H).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 49

42
2-(4-amino imidazolyl)-2-phenyl-1-pyrrolidinylethan-1-one dihydrochloride [ No CAS ]
[ 159634-94-3 ]
[ 220540-73-8 ]

Yield	Reaction Conditions	Operation in experiment
31.5%	Stage #1: (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In tetrahydrofuran at 0℃; for 1.5h; Stage #2: 2-(4-amino imidazolyl)-2-phenyl-1-pyrrolidinylethan-1-one dihydrochloride In tetrahydrofuran at 0℃; for 4h;	2-51 N-Methyl morpholine (0.28 mL, 8.32 mm, 1 eq) was added to a stirred slurry of 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.46 g, 2.57 mm, 1 eq) and (2R)-2-(2-[(tert-butoxy)carbonylamino]-2-methylpropanoylamino}-3-indol-3-ylpropanoic acid (1 g, 2.57 mm) in 10 mL of anhydrous tetrahydrofuran cooled to less than 0° C. After 1.5 hours, 2-(4-aminoimidazolyl)-2-phenyl-1-pyrrolidinylethan-1-one, hydrochloride (0.97 g, 2.82 mm, 1.1 eq) was added and stirring was continued at ice bath temperatures. The reaction was stirred for 4 hours and quenched by the addition of 15 mL of deionized water and ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution, dried over magnesium sulfate and the volatiles were removed under vacuum to give the crude product as a light purple foam (1.4 g, 84%) The crude product was purified by preparative chromatography to provide 0.52 g (31.5%) of the product as a foam. 1H nmr (CDCl3): δ 1.10-1.40 (m, 15H), 1.67-1.92 (m, 3H), 2.92-3.60 (m, %H), 4.90 (s, broad, 1H), 5.33 (s, broad, 1H), 5.85 (d, 1H), 6.80-7.05 (m, 3H), 7.13-7.39 (m, 10H), 7.44-7.80 (m, 2H), 8.96 (s, broad, 1H), 10.20 (s, broad, 1H).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 131-132

43
[ 1203798-53-1 ]
[ 159634-94-3 ]
[ 1415234-49-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / N,N-dimethyl-formamide / 24 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 20.75 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US2012/302540, 2012, A1

44
[ 1203798-53-1 ]
[ 159634-94-3 ]
[ 1415235-76-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 24h;	1.9.1 A mixture comprising 4-(4-fluorophenyl)-2-methyl-2,7-diazaspiro[4.5]decan-1-one (ASW MedChem) (269 mg, 0.899 mmol), (R)-2-(2-(tert-butoxycarbonylamino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acid (Intermediate 3C) (350 mg, 0.899 mmol) and DIPEA (0.628 ml, 3.59 mmol) in DMF (4 ml) was treated with T3P (50% in DMF, 0.525 ml, 1.797 mmol) and stirred at RT for 24 hours. The reaction mixture was diluted with water (5 ml) and extracted with EtOAc. The organic portion was dried (MgSO4) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 1% MeOH in DCM afforded the title compound;LC-MS Rt 2.57 mins; MS m/z 634 [M+H]+; Method LowpH_v002.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US2012/302540, 2012, A1 Location in patent: Page/Page column 45

45
[ 1203797-39-0 ]
[ 159634-94-3 ]
[ 1415235-84-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 2.33333h;	3.0.1 A mixture comprising (R)-3-(benzyloxy)-2-(2-(tert-butoxycarbonylamino)-2-methyl propanamido)propanoic acid (Intermediate 3A) (300 mg, 0.789 mmol), rac-2-methyl-3-phenyl-2,6-diazaspiro[3.5]nonan-1-one (Intermediate 2A) (182 mg, 0.789 mmol) and DIPEA (0.551 ml, 3.15 mmol) in DMF (4 ml) was treated with T3P (amide coupling agent 50% in DMF, 0.460 ml, 1.577 mmol) and stirred at RT for 17 hours. The reaction mixture was diluted with water (5 ml) and extracted with EtOAc. The organic portion was dried (MgSO4) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 1% MeOH in DCM afforded the title compound;LC-MS Rt 2.45 mins; MS m/z 594[M+H]+; Method LowpH_v002.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US2012/302540, 2012, A1 Location in patent: Page/Page column 51

46
[ 1203797-39-0 ]
[ 159634-94-3 ]
N-((2R)-3-(1H-indol-3-yl)-1-(2-isopropyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-amino-2-methylpropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / N,N-dimethyl-formamide / 2.33 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 17 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US2012/302540, 2012, A1

47
[ 1450600-46-0 ]
[ 159634-94-3 ]
C₃₃H₄₁N₅O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.5h; Stage #2: 2'-oxa-1,2,3,5,6,7-hexahydrospiro-4H-azepine-4,3'-3H-indole With N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; for 15h;	6.2.6 General procedure for the coupling reaction General procedure: N-Boc protected amino acid or N-Boc-Aib-TrpOH (0.57 mmol) was suspended in CH2Cl2 (2.5 mL) at 0 °C. EDC·HCl (248 mg, 1.3 mmol) and HOBt (175 mg, 1.3 mmol) were added to the mixture that was stirred for 30 min. Compound 6a or 6b or 10a or 11a (0.52 mmol), suspended in CH2Cl2 (2.5 mL) and DIPEA (222 μL 0.57 mmol), were added in sequence to the reaction mixture containing activated amino acid and the mixture was warmed at 25 °C under stirring for 15 h (TLC: CH2Cl2/MeOH, 10:1). The organic layer was washed with H2O (1.5 mL) and dried over Na2SO4. The solvent was evaporated. The crude mixture was purified on silica gel (CH2Cl2/MeOH, from 1:0 to 100:1). Yields are reported in Table 3. It is possible to separate the mixture of (-)-8a/(+)-9a using flash chromatography (cyclohexane/AcOEt, 1:1), while any attempt to separate 8b/9b and 12b/13b mixture failed.

Reference： [1]Pellegrino, Sara; Ruscica, Massimiliano; Magni, Paolo; Vistoli, Giulio; Gelmi, Maria Luisa [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5470 - 5479]

48
C₁₆H₂₅N₃O*2ClH [ No CAS ]
[ 159634-94-3 ]
[ 339539-90-1 ]
(S,R)-{1-[2-[3-benzyl-3-(N,N',N'-trimethyl-hydrazinocarbonyl)piperidin-1-yl]-1-(1H-indol-3-ylmethyl)-2-oxo-ethylcarbamoyl]-1-methylethyl}carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 3-hydroxy-3,4-dihydrobenzotriazine-4-one In dichloromethane at 20℃; Stage #2: C₁₆H₂₅N₃O*2ClH In dichloromethane at 20℃;

Reference： [1]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

49
C₁₆H₂₅N₃O*2ClH [ No CAS ]
[ 159634-94-3 ]
[ 339539-90-1 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; 3-hydroxy-3,4-dihydrobenzotriazine-4-one In dichloromethane at 25℃; for 20h; Inert atmosphere;

Reference： [1]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

50
[ 30992-29-1 ]
[ 153-94-6 ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	at 38℃;

Reference： [1]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

51
(R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid methyl ester [ No CAS ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
2.48 kg	With sodium hydroxide In tert-butyl methyl ether; water at 20℃; Large scale;

Reference： [1]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

52
[ 159634-94-3 ]
RC-1291 fumarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: 3-hydroxy-3,4-dihydrobenzotriazine-4-one; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C 1.2: 20 °C 2.1: hydrogenchloride / ethyl acetate 3.1: sodium carbonate / dichloromethane
	Multi-step reaction with 3 steps 1: triethylamine; 3-hydroxy-3,4-dihydrobenzotriazine-4-one; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 h / 25 °C / Inert atmosphere 2: hydrogenchloride / ethyl acetate 3: sodium carbonate / dichloromethane

Reference： [1]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]
[2]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

53
[ 159634-94-3 ]
[ 249921-19-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 3-hydroxy-3,4-dihydrobenzotriazine-4-one; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C 1.2: 20 °C 2.1: hydrogenchloride / ethyl acetate
	Multi-step reaction with 2 steps 1: triethylamine; 3-hydroxy-3,4-dihydrobenzotriazine-4-one; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 h / 25 °C / Inert atmosphere 2: hydrogenchloride / ethyl acetate

Reference： [1]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]
[2]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

54
(R)-(+)-tryptophan methyl ester hydrochloride [ No CAS ]
[ 159634-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; 3-hydroxy-3,4-dihydrobenzotriazine-4-one; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 3 h / 38 °C / Inert atmosphere; Large scale 2: sodium hydroxide / water; tert-butyl methyl ether / 20 °C / Large scale

Reference： [1]Paul, Bernhard J.; Littler, Benjamin J.; Jos, Frederic; Vogt, Paul F.; Pines, Seemon H. [Organic Process Research and Development, 2006, vol. 10, # 2, p. 339 - 345]

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. :	159634-94-3	MDL No. :	MFCD08704784
Formula :	C₂₀H₂₇N₃O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DSCBSBPYDCIRPP-OAHLLOKOSA-N
M.W :	389.45	Pubchem ID :	15895387
Synonyms :

Num. heavy atoms :	28
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.45
Num. rotatable bonds :	10
Num. H-bond acceptors :	5.0
Num. H-bond donors :	4.0
Molar Refractivity :	105.47
TPSA :	120.52 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.33 cm/s

Log Po/w (iLOGP) :	1.87
Log Po/w (XLOGP3) :	1.9
Log Po/w (WLOGP) :	2.58
Log Po/w (MLOGP) :	1.05
Log Po/w (SILICOS-IT) :	2.39
Consensus Log Po/w :	1.96

[ CAS No. 159634-94-3 ] {[proInfo.proName]}

Quality Control of [ 159634-94-3 ]

Related Doc. of [ 159634-94-3 ]

Product Details of [ 159634-94-3 ]

Calculated chemistry of [ 159634-94-3 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 159634-94-3 ]

Application In Synthesis of [ 159634-94-3 ]

[ 159634-94-3 ] Synthesis Path-Downstream 1~54

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 :	0.0
Bioavailability Score :	0.56

Log S (ESOL) :	-3.03
Solubility :	0.364 mg/ml ; 0.000935 mol/l
Class :	Soluble
Log S (Ali) :	-4.05
Solubility :	0.0344 mg/ml ; 0.0000884 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.82
Solubility :	0.00595 mg/ml ; 0.0000153 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.42

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	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
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P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
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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.
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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.
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P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
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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:
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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
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P331	Do NOT induce vomiting.
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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
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P413
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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