[ CAS No. 29840-56-0 ] {[proInfo.proName]}

Name: 29840-56-0|Methyl 5-aminopentanoate hydrochloride|97%
Brand: Ambeed
SKU: A633490
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Quality Control of [ 29840-56-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 29840-56-0 ]

Product Details of [ 29840-56-0 ]

CAS No. :	29840-56-0	MDL No. :	MFCD13368250
Formula :	C₆H₁₄ClNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FAKIZCQRTPAOSH-UHFFFAOYSA-N
M.W :	167.63	Pubchem ID :	13672034
Synonyms :

Calculated chemistry of [ 29840-56-0 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.83
Num. rotatable bonds :	5
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.91
TPSA :	52.32 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.63 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.97
Log Po/w (WLOGP) :	1.09
Log Po/w (MLOGP) :	0.75
Log Po/w (SILICOS-IT) :	0.34
Consensus Log Po/w :	0.63

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.16
Solubility :	11.6 mg/ml ; 0.0691 mol/l
Class :	Very soluble
Log S (Ali) :	-1.66
Solubility :	3.7 mg/ml ; 0.0221 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.18
Solubility :	11.0 mg/ml ; 0.0659 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.27

Safety of [ 29840-56-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313-P362-P403+P233-P405-P501	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 29840-56-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 29840-56-0 ]
Downstream synthetic route of [ 29840-56-0 ]

[ 29840-56-0 ] Synthesis Path-Upstream 1~6

1
[ 29840-56-0 ]
[ 27219-07-4 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 10, p. 2730 - 2742

2
[ 67-56-1 ]
[ 660-88-8 ]
[ 29840-56-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	at 0 - 20℃;	5-Aminovaleric acid 12 (2 g; 17.07 mmol) was dissolved in CH3-OH (25 mL). The solution was cooled down to -10 C, and SOCl2(2.84 mL; 39.06 mmol) was added dropwise onto the stirred solution.Mixture was warmed to room temperature and left to reactovernight. Solvent was evaporated under vacuum and the solidresidue triturated in Et2O. Final product was a white solid(2.751 mg; 96percent). Rf 0.7 (DCM/MeOH/NH4OH 85:14:1); 1H NMR(MeOD, 400 MHz) d 3.69 (s, 3H), 2.96 (m, 2H), 2.41–2.45 (m, 2H),1.70–1.74 (m, 4H); 13C NMR (MeOD, 100 MHz) d 173.9, 50.9,39.1, 32.7, 26.5, 21.5; MS (ESI), m/z calculated for [C6H13NO2+H+]= 132.1, found 132.1.
95%	at 0 - 20℃; for 2 h; Cooling with ice	General procedure: To a solution of amino substituted fatty acid derivatives 10a-10d (10 mmol) in 20 mL methanol was added thionyl chloride (20 mmol) dropwise under ice bath. After stirring at room temperature for about 2 h, the solution was evaporated to give the desired products 11a-11d.
92%	at 20℃; Reflux	General procedure: To a solution of the amino acid 1a–1e (22.45 mmol, 1 mol equiv) in 20–30 cm3 of dry methanol in a two-neck flask with a reflux condenser 2.3 cm3 thionyl chloride (31.43 mmol,1.4 mol equiv) was added drop-wise over 5–10 min. After the addition was complete, the mixture was heated to reflux for 3 h. The reaction mixture was left to stir over night at room temperature. After the reaction was complete, the solvent was removed by evaporation (RVE). The white or light-yellow solid was washed with n-hexane(2 9 50 cm3), and evaporated with another portion of n-hexane. The product was dried at low pressure. Methyl 5-aminopentanoate hydrochloride (2a) was isolatedas semi-transparent solid in 3.46 g (92percent yield). M.p.:141–143 C (146.3 C [42]); 1H NMR (300 MHz, D2O):d = 3.57 (s, 3H COOCH3), 2.88 (t, 2H, J(4,5) = 7.0 Hz,C5-H2), 2.30–2.35 (m, 2H, C2-H2), 1.53–1.59 (m, 4H, C3-H2 and C4-H2) ppm; 13C NMR (75 MHz, D2O): d = 179.2(C1), 54.7 (COOCH3), 41.6 (C5), 35.5 (C2), 28.6 (C4),23.6 (C3) ppm; IR (solid): m = 3021 (s), 2945 (s), 1735 (s),1596 (m), 1576 (m), 1519 (s), 1474 (w), 1444 (w), 1414(w), 1346 (w), 1271 (m), 1187 (s), 1152 (m), 1068 (w),1055 (m), 984 (w), 952 (m), 899 (w), 882 (w), 865 (w), 748(s), 651 (w) cm-1.

79%

at -10℃; for 3 h; Reflux

To a stirred solution 5-aminopentanoic acid (500 mg, 4.27 mmol) in dry MeOH (5 mL) kept at -10°C, SOCl₂ (1.1 mL, d=1.631 g/mL, 15 mmol) was dropwise added. The obtained reaction mixture was refluxed for 3h. Then, SOCl₂ excess and MeOH were distilled under reduced pressure, using a NaOH trap. The product was obtained as a white solid in 79percent yield (645 mg) and used in the following reaction without any further purification. NMR (300 MHz, CDCl₃, δ) : 8.28 (bs, 3H, NH₃) ; 3.67 (s, 3H, OCH₃) ; 3.04 (m, 2H, CNH₂); 2.38 (t, 2H, CH₂CO) ; 1.8-1.73 (m, 4H, CH₂CH₂).

Reference： [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 20, p. 6094 - 6103
[2] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 10, p. 2730 - 2742
[3] Angewandte Chemie - International Edition, 2013, vol. 52, # 28, p. 7228 - 7232[4] Angew. Chem., 2013, vol. 125, # 28, p. 7369 - 7373,5
[5] Organic and Biomolecular Chemistry, 2016, vol. 14, # 25, p. 6010 - 6023
[6] European Journal of Medicinal Chemistry, 2018, vol. 154, p. 44 - 59
[7] Monatshefte fur Chemie, 2018, vol. 149, # 5, p. 901 - 911
[8] Patent: WO2017/187352, 2017, A1, . Location in patent: Page/Page column 20; 22; 23
[9] Journal of Medicinal Chemistry, 1990, vol. 33, # 1, p. 223 - 228
[10] Patent: EP1489078, 2004, A1, . Location in patent: Page 194-195
[11] Patent: EP1582521, 2005, A1, . Location in patent: Page/Page column 120
[12] Patent: EP1666455, 2006, A1, . Location in patent: Page/Page column 45
[13] Patent: WO2007/67814, 2007, A2, . Location in patent: Page/Page column 69-70
[14] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1185 - 1190
[15] ChemMedChem, 2016, vol. 11, # 11, p. 1172 - 1187
[16] European Journal of Medicinal Chemistry, 2017, vol. 141, p. 404 - 416

3
[ 675-20-7 ]
[ 67-56-1 ]
[ 29840-56-0 ]

Yield	Reaction Conditions	Operation in experiment
72%	With hydrogenchloride In water at 20 - 55℃; for 20 h; Inert atmosphere	To a stirred solution of piperidin-2-one 10-lA (500 mg, 5.05 mmol) in MeOH (10 mL) was passed HCl gas. The reaction mixture was stirred at RT for 4 hr under N₂ atmosphere. Then reaction mixture warmed to 55 °C and stirring continued for 16 hr. Reaction solvents were evaporated under reduced pressure and the crude residue was washed with diethyl ether to afford 10-2A (608 mg, 129.57 mmol, 72percent yield) as an off-white solid.

Reference： [1] Patent: WO2016/154241, 2016, A1, . Location in patent: Paragraph 443; 444

4
[ 660-88-8 ]
[ 29840-56-0 ]

Reference： [1] Patent: US4722810, 1988, A,
[2] Patent: US4742068, 1988, A,

5
[ 77-76-9 ]
[ 660-88-8 ]
[ 29840-56-0 ]

Reference： [1] Journal of Organic Chemistry, 2007, vol. 72, # 16, p. 6162 - 6170

6
[ 67-56-1 ]
[ 627-95-2 ]
[ 29840-56-0 ]

Reference： [1] Journal of Medicinal Chemistry, 2017, vol. 60, # 2, p. 787 - 796

[ 29840-56-0 ] Synthesis Path-Downstream 1~88

1
[ 590-28-3 ]
[ 29840-56-0 ]
[ 18126-15-3 ]

Reference： [1]Pharmaceutical Chemistry Journal,1967,p. 436 - 439
Khimiko-Farmatsevticheskii Zhurnal,1967,p. 9 - 13

2
[ 67402-86-2 ]
[ 29840-56-0 ]
[ 115932-99-5 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 223 - 228

3
[ 116-31-4 ]
[ 29840-56-0 ]
[ 94887-45-3 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1984,p. 1669 - 1673
Zhurnal Organicheskoi Khimii,1984,vol. 20,p. 1831 - 1835

4
[ 13734-34-4 ]
[ 29840-56-0 ]
Boc-Phe-δApe-OMe [ No CAS ]

Reference： [1]Farmaco, Edizione Scientifica,1987,vol. 42,p. 815 - 822

5
[ 29840-56-0 ]
[ 102697-90-5 ]
[ 102697-95-0 ]

Reference： [1]Liebigs Annalen der Chemie,1986,vol. 1986,p. 1528 - 1539

6
[ 29840-56-0 ]
(1S,3S)-3-((E)-3-Hydroxy-oct-1-enyl)-2,2-dimethyl-cyclopropanecarboxylic acid benzotriazol-1-yl ester [ No CAS ]
[ 102697-90-5 ]

Reference： [1]Liebigs Annalen der Chemie,1986,vol. 1986,p. 1528 - 1539

7
[ 29840-56-0 ]
(1R,3R)-2,2-Dimethyl-3-{(E)-3-[(S)-(tetrahydro-pyran-2-yl)oxy]-oct-1-enyl}-cyclopropanecarboxylic acid benzotriazol-1-yl ester [ No CAS ]
[ 102697-91-6 ]

Reference： [1]Liebigs Annalen der Chemie,1986,vol. 1986,p. 1528 - 1539

8
[ 29840-56-0 ]
[ 39947-70-1 ]
[ 116952-12-6 ]
(Z)-dimethyl 2-formyl-4-azanon-2-ene-1,9-dioate [ No CAS ]

Reference： [1]Chemische Berichte,1989,vol. 122,p. 83 - 94

9
[ 29840-56-0 ]
(E)4-(mesyloxymethylene)-2-oxabicyclo<3.3.0>-6-octen-3-one [ No CAS ]
5-[(3aR,6aR)-2-Oxo-6,6a-dihydro-3aH-cyclopenta[b]furan-(3E)-ylidenemethyl]-amino}-pentanoic acid methyl ester [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,1993,vol. 29,p. 635 - 641
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 743 - 750

10
[ 29840-56-0 ]
3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chloride [ No CAS ]
[ 246154-02-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5526 - 5530

11
[ 10211-88-8 ]
[ 29840-56-0 ]
[ 913338-39-3 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 6094 - 6103

12
[ 1474-14-2 ]
[ 29840-56-0 ]
[ 913338-69-9 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 6094 - 6103

13
[ 29840-56-0 ]
[ 862510-14-3 ]
N-[[ethyl 4-(4-chlorophenyl)-6-phenyl-3-pyridine-carboxylate]-2-yl]caproic acid methyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 8488 - 8494

14
[ 29840-56-0 ]
[ 862510-15-4 ]
N-[[ethyl 4-(3,4-dichlorophenyl)-6-phenyl-3-pyridine-carboxylate]-2-yl]caproic acid methyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 8488 - 8494

15
[ 77-76-9 ]
[ 660-88-8 ]
[ 29840-56-0 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 6162 - 6170

16
triethylammonium 5-N-Boc-guanidinocarbonyl-1H-pyrrole-2-carboxylate [ No CAS ]
[ 29840-56-0 ]
[ 948863-37-4 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 6162 - 6170

17
[ 29840-56-0 ]
C₁₂H₁₇N₅O₄ [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 6162 - 6170

18
[ 29840-56-0 ]
5-[2-(3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-propylamino]-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 6094 - 6103

19
[ 29840-56-0 ]
5-[2-(3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-propionylamino]-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 6094 - 6103

20
[ 29840-56-0 ]
[ 908020-51-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5526 - 5530

21
[ 29840-56-0 ]
[ 246153-83-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5526 - 5530

22
[ 29840-56-0 ]
5-(9-chloro-3-methyl-4-oxo-4H-isoxazolo[4,3-c]quinolin-5-yl)-pentanoic acid (3,4,5-trimethoxy-phenyl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5526 - 5530

23
[ 29840-56-0 ]
5-[((2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-Hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydro-picene-2-carbonyl)-amino]-pentanoic acid [ No CAS ]

Reference： [1]Russian Journal of Organic Chemistry,2000,vol. 36,p. 982 - 995

24
[ 29840-56-0 ]
[ 251456-59-4 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4669 - 4679

25
[ 29840-56-0 ]
5-(4-dimethylaminobenzoyl)aminovaleric acid hydroxamate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4669 - 4679

26
[ 29840-56-0 ]
[ 251456-82-3 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4669 - 4679

27
[ 29840-56-0 ]
5-[((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-Hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysene-3a-carbonyl)-amino]-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 1069 - 1083

28
[ 29840-56-0 ]
5-{5-[((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-Hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysene-3a-carbonyl)-amino]-pentanoylamino}-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 1069 - 1083

29
[ 29840-56-0 ]
5-{8-[((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-Hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysene-3a-carbonyl)-amino]-octanoylamino}-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 1069 - 1083

30
[ 29840-56-0 ]
5-[[[5-methoxy-3-(1-methylethoxy)benzo[b]thien-2-yl]carbonyl]amino]pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4597 - 4614

31
[ 29840-56-0 ]
H-Phe-δApe-OMe*TFA [ No CAS ]

Reference： [1]Farmaco, Edizione Scientifica,1987,vol. 42,p. 815 - 822

32
[ 29840-56-0 ]
5-{Acetyl-[(3aR,6aR)-2-oxo-6,6a-dihydro-3aH-cyclopenta[b]furan-(3E)-ylidenemethyl]-amino}-pentanoic acid methyl ester [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,1993,vol. 29,p. 635 - 641
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 743 - 750

33
[ 29840-56-0 ]
5-{Benzoyl-[(3aR,6aR)-2-oxo-6,6a-dihydro-3aH-cyclopenta[b]furan-(3E)-ylidenemethyl]-amino}-pentanoic acid methyl ester [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,1993,vol. 29,p. 635 - 641
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 743 - 750

34
[ 29840-56-0 ]
5-{Benzoyl-[(3aR,6aR)-2-oxo-6,6a-dihydro-3aH-cyclopenta[b]furan-(3Z)-ylidenemethyl]-amino}-pentanoic acid methyl ester [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,1993,vol. 29,p. 635 - 641
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 743 - 750

35
[ 29840-56-0 ]
[ 17994-87-5 ]

Reference： [1]Pharmaceutical Chemistry Journal,1967,p. 436 - 439
Khimiko-Farmatsevticheskii Zhurnal,1967,p. 9 - 13

36
[ 29840-56-0 ]
[ 4635-59-0 ]
[ 609805-78-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In chloroform; at 0 - 20℃; for 2h;	(1) 5-Aminovaleric acid (7.35 g) is dissolved in methanol (50 ml), thereto is added dropwise thionyl chloride (4.9 ml) under ice-cooling, and the reaction solution is warmed to room temperature and stirred for 17 hours. The reaction solution is concentrated under reduced pressure, and the resulting residue is suspended in diethyl ether and the precipitates are collected by filtration to give methyl 5-aminovalerate hydrochloride (9.93 g). APCI-MS M/Z:132[M+H]+.(2) Methyl 5-aminovalerate hydrochloride (1.68 g) obtained in (1) is suspended in chloroform (20 ml). To the suspension, triethylamine (2.54 g) is added under ice-cooling, and then 4-chlorobutyryl chloride (1.55 g) is added dropwise. The reaction solution is warmed to room temperature, stirred for 2 hours, ice-water is poured to the reaction solution and the mixture is extracted with chloroform. The organic layer is washed with 10 % hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over sodium sulfate. The resultant is evaporated to remove the solvent under reduced pressure to give methyl 5-(4-chlorobutyrylamino)pentanoate (2.34 g). APCI-MS M/Z:236/238[M+H]+.(3) Methyl 5-(4-chlorobutyrylamino)pentanoate (2.33 g) obtained in (2) is dissolved in N,N-dimethylacetamide (20 ml) and 60 % sodium hydride in oil (0.47 g) is added thereto gradually under ice-cooling. The reaction solution is warmed to room temperature, stirred for 20 hours and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: chloroform followed by chloroform/ethyl acetate = 20/1) to give methyl 5-(2-oxopyrrolidin-1-yl)pentanoate (2.15 g). APCI-MS M/Z:200[M+H]+.(4) Methyl 5-(2-oxo-pyrrolidin-1-yl)pentanoate (1.00 g) obtained in (3) is dissolved in methanol (20 ml), thereto is added 4 N aqueous sodium hydroxide solution (2.5 ml), the reaction solution is warmed to room temperature and stirred for 18 hours. The reaction solution is washed with diethyl ether, thereto is added 2 N hydrochloric acid (5.0 ml), and then concentrated under reduced pressure. The resulting residue is extracted with chloroform and dried over sodium sulfate. The resultant is evaporated to remove solvent under reduced pressure to give the title compound (0.90 g). ESI-MS M/Z:184[M-H]-.
	With triethylamine; In chloroform; at 0 - 20℃; for 2h;	(2) Methyl 5-aminovalerate hydrochloride (1.68 g) obtained in (1) above is suspended in chloroform (20 ml), and to the suspension is added triethylamine (2.54 g) under ice-cooling, followed by dropwise addition of 4-chlorobutyryl chloride (1.55 g). The reaction solution is warmed to room temperature and stirred for 2 hours. Ice-water is poured to the reaction solution and the mixture is extracted with chloroform. The organic layer is washed with 10 % hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over sodium sulfate. The solvent is evaporated under reduced pressure to give methyl 5-[(4-chlorobutanoyl)amino]-pentanoate (2.34 g). APCI-MS M/Z:236/238[M+H]+.
	With triethylamine; In chloroform; at 0 - 20℃; for 2h;	Methyl 5-aminovalerate hydrochloride (1.68 g) obtained in (1) above is suspended in chloroform (20 ml), and to the suspension is added triethylamine (2.54 g) under ice-cooling, followed by dropwise addition of 4-chlorobutyryl chloride (1.55 g). The reaction solution is warmed to room temperature and stirred for 2 hours. Ice-water is poured to the reaction solution and the mixture is extracted with chloroform. The organic layer is washed with 10 % hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over sodium sulfate. The solvent is evaporated under reduced pressure to give methyl 5-[(4-chlorobutanoyl)amino]pentanoate (2.34 g). APCI-MS M/Z:236/238[M+H]+

Reference： [1]Patent: EP1489078,2004,A1 .Location in patent: Page 194-195
[2]Patent: EP1582521,2005,A1 .Location in patent: Page/Page column 120
[3]Patent: EP1666455,2006,A1 .Location in patent: Page/Page column 45

37
[ 29840-56-0 ]
[ 93206-09-8 ]
[ 727736-40-5 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 48h;	(1) Methyl 5-aminovalerate hydrochloride (3.35 g) obtained in Reference Example 6(1), [2-(benzyloxy)ethoxy]acetic acid (4.63 g) obtained in Reference Example 4(1) and 1-hydroxybenzotriazole (3.78 g) are dissolved in N,N-dimethylformamide (80 ml). To the mixture are added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.37 g) and triethylamine (3.35 ml) successively under ice-cooling, and the mixture is stirred at room temperature for 2 days. The reaction solution is concentrated under reduced pressure, and the resulting residue is diluted with ice-water and extracted with ethyl acetate. The organic layer is washed with aqueous sodium hydrogen carbonate solution, water and saturated brine successively, dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 1:1 followed by ethyl acetate) to give methyl 5-([2-(benzyloxy)ethoxy]acetyl}amino)pentanoate (5.56 g). APCI-MS M/Z:324[M+H]+.
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 48h;	(1) Methyl 5-aminovalerate hydrochloride (3.35 g) obtained in Reference Example 6(1), [2-(benzyloxy)-ethoxy]acetic acid (4.63 g) obtained in Reference Example 4(1) and 1-hydroxybenzotriazole (3.78 g) are dissolved in N,N-dimethylformamide (80 ml). To the mixture are added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.37 g) and triethylamine (3.35 ml) successively under ice-cooling, and the mixture is stirred at room temperature for 2 days. The reaction solution is concentrated under reduced pressure, and the resulting residue is diluted with ice-water and extracted with ethyl acetate. The organic layer is washed with aqueous sodium hydrogen carbonate solution, water and saturated brine successively, dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 1:1 followed by ethyl acetate) to give methyl 5-([2-(benzyloxy)ethoxy]acetyl}amino)pentanoate (5.56 g). APCI-MS M/Z:324[M+H]+

Reference： [1]Patent: EP1582521,2005,A1 .Location in patent: Page/Page column 121
[2]Patent: EP1666455,2006,A1 .Location in patent: Page/Page column 46

38
[ 2942-58-7 ]
[ 29840-56-0 ]
[ 189060-51-3 ]
[ 383669-14-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In N,N-dimethyl-formamide;	(1) To a solution of (3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-acetic acid (2.0 g, 4.18 mmol) and <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong> (0.77 g, 4.60 mmol) in N,N-dimethylformamide (20 ml) were added diethyl cyanophosphate (0.82 g, 5.02 mmol) and then triethylamine (1.1 g, 10.5 mmol). The mixture was stirred at room temperature for 30 minutes. This was diluted with ethyl acetate (100 ml), washed with water, 5% aqueous potassium hydrogen sulfate solution, saturated aqueous sodium hydrogen carbonate solution and saturated saline, dried with sodium sulfate, and then concentrated under reduced pressure. The residue was purified by recrystallization from ethyl acetate-hexane (1:1) to obtain methyl 5-[[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]amino]pentanoate (2.57 g, 4.35 mmol, quant) as colorless prisms. Melting point 84-85 C. [alpha]D22-190.6 (c=0.13, MeOH). IR numax (KBr) cm-1: 3600-3200 (br, OH, NH), 1738, 1660 (C=O). 1H-NMR (CDCl3) delta: 0.637 (3H, s), 1.046 (3H, s), 1.45-1.68 (4H, m), 2.337 (2H, t, J=7.0 Hz), 2.627 (1H, dd, J=5.6, 14.4 Hz), 2.840 (1H, dd, J=7.4, 14.4 Hz), 3.139 (1H, t, J=11.2 Hz), 3.237 (2H, q, J=6.2 Hz), 3.379 (1H, d, J=14.2 Hz), 3.606 (3H, s), 3.610 (1H, dd, J=4.4, 11.2 Hz), 3.672 (3H, s), 3.892 (3H, s), 4.196 (1H, dd, J=4.4, 11.2 Hz), 4.401 (1H, dd, J=5.6, 7.4 Hz), 4.459 (1H, d, J=14.2 Hz), 5.88-5.94 (1H, br), 6.151 (1H, s), 6.601 (1H, s), 6.96-7.36 (5H, m). Elemental analysis (C30H39N2O8Cl.H2O) Cal'd: C, 59.16; H, 6.78; N, 4.60. Found: C, 59.05; H, 6.64; N, 4.29.

Reference： [1]Patent: US2003/78251,2003,A1

39
[ 29840-56-0 ]
[ 1077-28-7 ]
methyl 5-[5-(1,2-dithiolan-3-yl)pentanoylamino]pentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium chloride; triethylamine; 1,1'-carbonyldiimidazole; In N-methyl-acetamide; water;	EXAMPLE 118 Methyl-5-[5-(1,2-dithiolan-3-yl)pentanoylamino]pentanoate (Compound No. 1-2657 Methyl Ester) STR132 The reaction was carried out as described in Example 47, but using 1.00 g of D,L-alpha-lipoic acid, 40 ml of anhydrous dimethylformamide, 0.86 g of N,N'-carbonyldiimidazole, 0.74 ml of triethylamine and 0.89 g of <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong>. The solvent was removed form the reaction mixture by evaporation under reduced pressure, and water was added to the residue, after which it was extracted with ethyl acetate. The extraction solution was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The ethyl acetate was removed from the extraction solution by evaporation under reduced pressure, and the residue was subjected to silica gel column chromatography, using 2:1 and 1:0 by volume mixtures of ethyl acetate and hexane as the eluent. It was then recrystallized from ethyl acetate, to obtain 1.10 g of the title compound as pale yellow crystals, melting at 60 to 62 C.

Reference： [1]Patent: US6013663,2000,A

40
3β-acetoxy-20(29)-lupen-28-oyl chloride [ No CAS ]
betulic acid acetate [ No CAS ]
[ 29840-56-0 ]
methyl N-[3β-acetoxy-20(29)-lupen-28-oyl]-5-aminopentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In chloroform;	EXAMPLE 1 650 mg of <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong> and then 1.07 cm3 of triethylamine are added to 50 cm 3 of a chloroform solution of 3beta-acetoxy-20(29)-lupen-28-oyl chloride (prepared from 1.7 g of 3beta-acetoxy-20(29)-lupen-28-oic acid). The solution is then stirred for 20 hours at a temperature in the region of 20 C. After addition of 60 cm3 of distilled water, the organic phase is separated off and the aqueous phase is washed with a total of 40 cm3 of chloroform. The combined organic phases are washed with a total of 40 cm3 of distilled water, dried over anhydrous sodium sulphate and concentrated to dryness under reduced pressure (2.7 kPa) at a temperature in the region of 40 C. 1.9 g of a yellow foam is obtained which is chromatographed on a column with a diameter of 2.2 cm containing 38 g of silica.(0.02-0.045 mm) eluted with diisopropyl ether while collecting 10 cm3 fractions. After discarding the first 23 fractions, the following 17 are combined and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40 C. 1.1 g of methyl N-[3beta-acetoxy-20(29)-lupen-28-oyl]-5-aminopentanoate is thus obtained in the form of a white foam (Rf =0.35; silica thin film chromatography; eluent: diisopropyl ether).

Reference： [1]Patent: US5468888,1995,A

41
[ 110-87-2 ]
(RS)-2-(4-chlorobenzenesulfonylamino)-3-hydroxypropanoic acid [ No CAS ]
[ 29840-56-0 ]
[ 169184-50-3 ]

Yield	Reaction Conditions	Operation in experiment
		Example 10 Preparation of (RS)-2-(4-chlorobenzenesulfonylamino)-N-(4-methoxycarbonylbutyl)-3-(tetrahydropyran-2-yloxy)propanamide The procedure described in Example 1 was repeated, except that dihydropyran (2.9 ml) and methyl 5-aminopentanate hydrochloride (2.158 g) were successively reacted with (RS)-2-(4-chlorobenzenesulfonylamino)-3-hydroxypropanoic acid (3 g) to obtain (RS)-2-(4-chlorobenzenesulfonylamino)-N-(4-methoxycarbonylbutyl)-3-(tetrahydropyran-2-yloxy)propanamide (2.059 g). IR numax cm-1 (neat): 3373, 3305, 2945, 1736, 1655, 1439, 1340, 1167, 1124, 1086 1 H-NMR delta ppm (CDCl3): 1.259 (2H, t, J=7.1 Hz), 1.4-1.9 (8H, m), 2.329 (2H, t, J=7.1 Hz), 3.1-3.3 (2H, m), 3.3-3.5 (2H, m), 3.673 (3H, s), 3.7-3.9 (2H, m), 4.122 (1H, dd, J=14.4 Hz, J=7.1 Hz), 4.3-4.4 (1H, m), 7.4-7.6 (2H, m), 7.7-7.9 (2H, m) 13 C-NMR delta ppm (CDCl3): 14.15, 20.53, 24.93 and 25.00, 28.74, 30.57 and 30.65, 33.40, 39.23, 56.17 and 56.35, 64.42, 68.31, 100.91 and 101.06, 128.71 and 128.93, 137.44 and 137.84, 139.56 and 139.64, 168.46 and 168.68, 173.74 Fab-MS m/z: 477 (MH+), 393 (MH+ -THP)

Reference： [1]Patent: US5650428,1997,A

42
[ 1013-88-3 ]
[ 29840-56-0 ]
C₁₉H₂₁NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; for 18h;	Methylaminopentanoate hydrochloride ( 720 mg, 4.3 mmol) and benzophenoneimine (722 mg, 4.3 mmol) were stirred together in dichloromethane for 18 hrs. At this point, the reaction was washed with aqueous sodium bicarbonate and the organic layer EPO <DP n="68"/>dried with MgSO4 and evaporated to leave 1.3 g of a thick oil. The product (530 mg, 1.8 mmol) was then dissolved in THF (15 niL) and cooled (under N2) to -780C. DIBAL ( 2.0 niL, 1 M solution) was added dropwise and the reaction stirred for lhr. When TLC indicated the absence of the ester starting material and the presence of a aldehyde (via DNP stain), 1.3 eq of butyl magnesium bromide was added to the reaction. This was allowed to warm to room temperature over 2.5 hrs. The reaction was quenched with bicarbonate solution and the organic layer was dried and evaporated to give the imino alcohol (350 mg) as an oil. The imino alcohol (150 mg) was stirred with aqueous HCl (IM, ImL) and diethyl ether (5 niL) overnight. The aqueous layer was evaporated and 1 equivalent of 1-adamantylisocyanate was added as a solution in dichloromethane (5 ml) and triethylamine (0.5 mL). This was stirred overnight. The crude reaction was chromatographed on silica gel (1:1 EtOAc :hexanes) to give the product as an oil (35 mg). 1H NMR (300 MHz, CDCl3) delta= 4.22 (br, IH), 4.08 (br, IH), 3.91 (br, IH), 3.10 (m, IH), 2.30 (br, 2H), 2.2 - 1.0 (br m, 32 H)

Reference： [1]Patent: WO2006/45119,2006,A2 .Location in patent: Page/Page column 66-67

43
[ 911634-88-3 ]
[ 29840-56-0 ]
[3-oxo-1-(2-oxo-piperidin-1-ylmethyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-propyl]-(1S)-carbamic acid t-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%		77 mg (0.2 mmol) of [l-formyl-3-oxo-3-(3-trifluoromethyl-5,6-dihydro-8H-[l,2,4] triazolo[4,3-a]pyrazin-7-yl)-propyl]-lS-carbamic acid t-butyl ester was added 33 mg (0.2 mmol) of 5-amino-pentanoic acid methyl ester hydrochloric acid salt was dissolved in dichloroethane, followed by stirring for 30 minutes. 83 mg (0.4 mmol) of sodium triacetoxyborohydride was added to the solution, followed by stirring for about 1 hour and 40 minutes. The resulting solution was heated to 80C about 7 hours and concentrated, then the residue was purified by prep-TLC (10:1 CH Cl :MeOH) to give about 20 g of the title compound in a total yield of 21 %[598] 1K NMR (CD3OD) delta 6.5 (IH, m), 4.9-5.1 (2H, m), 4.0-4.4 (5H, m), 3.35-3.5 (3H, m), 2.6-2.8 (2H, m), 2.28 (2H, t, J = 6.0 Hz), 1.7-1.8 (4H, m), 1.36 (9H, s)[599] Mass (m/e) 475 (M+l)

Reference： [1]Patent: WO2006/104356,2006,A1 .Location in patent: Page/Page column 43

44
[ 29840-56-0 ]
[ 153248-79-4 ]
[ 911635-25-1 ]

Yield	Reaction Conditions	Operation in experiment
46%		A solution in which 576 mg (3.44 mg) of 5-amino-pentanoic acid methylester hydrochloric acid salt was dissolved in 1,2-dichloroethane 5 mL was added at room temperature to a solution in which 1.80 g of 3S-t-butoxycarbonylamino-4-oxo-butryic acid t-butylester (product of PREPARATION 41) was dissolved in 50 mL of 1,2-dichloroethane. After stirring at room temperature for 15 minutes, 1.46 g (6.88 mmol) of sodium triacetoxyborohydride was added thereto. After stirring at room temperature for 5 hours, the resulting solution was diluted with methyl chloridem and then washed with IN aqueous hydrochloric acid and saline, sequently. An organic layer thus obtained was dried over anhydrous magnesium sulfate, and the the solvent was distilled off under reduced pressure, then the residue, which was obtained by concentration under reduced pressure, was purified by column chromatography to give 568 mg of the title compound in a total yield of 46%.[788] 1K NMR (CDCl3) delta 5.34-5.29 (IH, m), 4.17 (IH, bra), 3.92-3.84 (IH, m),3.51-3.46 (IH, m), 3.27-3.23 (IH, m), 3.10-3.05 (IH, m), 2.56-2.51 (IH, m), 2.41-2.31 (3H, m), 1.82-1.75 (4H, m), 1.45 (9H, s)[789] Mass (m/e) 357 (M+l)

Reference： [1]Patent: WO2006/104356,2006,A1 .Location in patent: Page/Page column 58

45
t-butoxycarbonylphenylalanine (BOC-Phe) [ No CAS ]
[ 29840-56-0 ]
[ 543-27-1 ]
t-butoxycarbonyl-N-(5-methoxy-5-oxopentyl)-L-phenylalaninamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; In N-methyl-acetamide;	EXAMPLE 1 t-butoxycarbonyl-N-(5-methoxy-5-oxopentyl)-L-phenylalaninamide To a cold (ca -30), stirred solution of 26.5 g (0.1 mole) of t-butoxycarbonylphenylalanine (BOC-Phe) and 11.2 g (0.1 mole) of N-methylmorpholine in 150 ml of dimethylformamide (DMF) was added dropwise 13.2 ml (0.1 mole) of isobutylchloroformate. After warming and then holding the temperature at ca. -15 for about ten minutes, the solution was recooled to ca. -39. To the cold mixture was added additional N-methylmorpholine (12.3 ml, ca. 0.11 mole), followed by 18.5 g (0.11 mole) of <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong>. The mixture was allowed to warm to room temperature and to stand overnight. Solvent and other volatiles were removed by concentration in vacuo. The residue was triturated with ethyl acetate, which was then washed successively with water, 0.5 M potassium bisulfate, water, and again with 0.5 M potassium bisulfate, and then dried over magnesium sulfate, filtered, and concentrated to a white solid. After collection, the white solid was washed thoroughly with Skellysolve B to give 36.4 g of the title compound, m.p. 98-100. Recrystallization from ethyl acetate/Skellysolve B afforded analytically pure crystals. Analysis. Calcd. For C20 H30 N2 O5: C, 63.47; H, 7.99; N, 7.40. Found: C, 63.32; H, 8.03; N, 7.24.
	With 4-methyl-morpholine; In N-methyl-acetamide;	Example 1 t-butoxycarbonyl-N-(5-methoxy-5-oxopentyl)-L-phenylalaninamide To a cold (ca -30), stirred solution of 26.5 g (0.1 mole) of t-butoxycarbonylphenylalanine (BOC-Phe) and 11.2 g (0.1 mole) of N-methylmorpholine in 150 ml of dimethylformamide (DMF) was added dropwise 13.2 ml (0.1 mole) of isobutylchloroformate. After warming and then holding the temperature at ca. -15 for about ten minutes, the solution was recooled to ca. -39. To the cold mixture was added additional N-methylmorpholine (12.3 ml, ca. 0.11 mole), followed by 18.5 g (0.11 mole) of <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong>. The mixture was allowed to warm to room temperature and to stand overnight. Solvent and other volatiles were removed by concentration in vacuo. The residue was triturated with ethyl acetate, which was then washed successively with water, 0.5M potassium bisulfate, water, and again with 0.5M potassium bisulfate, and then dried over magnesium sulfate, filtered, and concentrated to a white solid. After collection, the white solid was washed thoroughly with Skellysolve B to give 36.4 g of the title compound, m.p. 98-100. Recrystallization from ethyl acetate/Skellysolve B afforded analytically pure crystals. Analysis. Calcd. For C20 H30 N2 O5: C, 63.47; H, 7.99; N, 7.40. Found: C, 63.32; H, 8.03; N, 7.24.
	With 4-methyl-morpholine; In N-methyl-acetamide;	EXAMPLE 1 t-butoxycarbonyl-N-(5-methoxy-5- oxopentyl)-L-phenylalaninamide To a cold (ca -30), stirred solution of 26.5 g (0.1 mole) of t-butoxycarbonylphenylalanine (BOC-Phe) and 11.2 g (0.1 mole) of N-methylmorpholine in 150 ml of dimethylformamide (DMF) was added dropwise 13.2 ml (0.1 mole) of isobutylchloroformate. After warming and then holding the temperature at ca. -15 for about ten minutes, the solution was recooled to ca. -39. To the cold mixture was added additional N-methylmorpholine (12.3 ml, ca. 0.11 mole), followed by 18.5 g (0.11 mole) of <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong>. The mixture was allowed to warm to room temperature and to stand overnight. Solvent and other volatiles were removed by concentration in vacuo. The residue was triturated with ethyl acetate, which was then washed successively with water, 0.5M potassium bisulfate, water, and again with 0.5M potassium bisulfate, and then dried over magnesium sulfate, filtered, and concentrated to a white solid. After collection, the white solid was washed thoroughly with Skellysolve B to give 36.4 g of the title compound, m.p. 98-100. Recrystallization from ethyl acetate/Skellysolve B afforded analytically pure crystals. Analysis. Calcd. For C20 H30 N2 O5: C, 63.47; H, 7.99; N, 7.40. Found: C, 63.32; H, 8.03; N, 7.24.

Reference： [1]Patent: US4603121,1986,A
[2]Patent: US4722922,1988,A
[3]Patent: US4495178,1985,A

46
[ 79-37-8 ]
[ 29840-56-0 ]
[ 91702-98-6 ]
(+/-)-5-[[2-[(acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]pentanoic acid, methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine;N-methyl-acetamide; In tetrahydrofuran; diethyl ether; dichloromethane; ethyl acetate;	(b) (+-)-5-[[2-[(Acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]pentanoic acid, methyl ester Oxalyl chloride (0.45 ml., 5.2 mmole) is added to a solution of (+-)-2-[(acetylthio)methyl]-3-phenylpropanoic acid (1.19 g., 5 mmole) in ethyl ether (10 ml.). This mixture is cautiously treated with a catalytic amount (3 drops) of dimethylformamide and then stirred for 1 hour at room temperature. The mixture is concentrated in vacuo, producing an oil which is dissolved in tetrahydrofuran (10 ml.) and again concentrated in vacuo. The resulting residue is dissolved in methylene chloride (6 ml.) and added dropwise over 10 minutes to a cold (-5), stirred solution of 5-aminovaleric acid, methyl ester, hydrochloride (0.91 g., 5.4 mmole) and diisopropylethylamine (1.96 ml., 11.25 mmole) in methylene chloride (11 ml.). After stirring in the cold (-5) for 2.5 hours the mixture is allowed to warm to room temperature and allowed to stir overnight. The next day, the mixture is concentrated in vacuo and the residue is taken up into ethyl acetate (60 ml.) and filtered to remove diisopropylethylamine hydrochloride. The filtrate is washed sequentially with 10% potassium bisulfate, water, 50% saturated sodium bicarbonate, and 50% brine (3*20 ml. each). The organic layer is dried (Na2 SO4) and concentrated to give a very light yellow oil (1.49 g.). This oil is applied to a column of 115 g. of silica gel (230-400 mesh) and eluted with 5:2 hexane/acetone to yield 1.41 g. of (+-)-5-[[2-[(acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]pentanoic acid, methyl ester as a colorless oil.

Reference： [1]Patent: US4722810,1988,A

47
[ 660-88-8 ]
[ 29840-56-0 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In methanol;	(a) 5-Aminovaleric acid, methyl ester, hydrochloride Thionyl chloride (2.93 ml., 40 mmole) is added, dropwise with stirring, to a cold suspension of 5-aminovaleric acid (2.34 g., 20 mmole) in methanol (25 ml.) at a rate so as to maintain the reaction temperature between -5 and -10. After the addition of the thionyl chloride is completed, the mixture is allowed to warm to room temperature and left to stir overnight. The mixture is concentrated in vacuo to give white crystals which are triturated in ether (twice) to give 2.68 g. of 5-aminovaleric acid, methyl ester, hydrochloride as white solids; m.p. 132-137 (softens at 86).
		a. Methyl 5-aminopentanoate Hydrochloride The title compound was prepared using the method of Example 9a after substituting an equivalent amount of 5-aminovaleric acid for 4-aminobutyric acid as a starting material. The title compound was isolated as a white solid, mp 139-142 C.

Reference： [1]Patent: US4722810,1988,A
[2]Patent: US4742068,1988,A

48
[ 1003-29-8 ]
[ 29840-56-0 ]
[ 185610-63-3 ]

Yield	Reaction Conditions	Operation in experiment
300 g (91.1%)	With triethylamine;silica gel; In diethyl ether; chloroform;	EXAMPLE 1 Preparation of 5-[[(1H-pyrrol-2-yl)methylen]amino]pentanoate To a stirred solution of 150 g of 1H-pyrrol-2-carboxaldehyde in 1500 g of trichloromethane were added 690 g of 50 nm molecular sieves. A hot solution of 264 g of <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong> in 1500 g of trichloromethane was added. After stirring for 5 minutes, 465 g of triethylamine was added over ten minutes. The reaction mixture was stirred for 20 hours at ambient temperature. The reaction mixture was filtered over diatomaceous earth and the filtrate was concentrated by evaporation of the solvent. The concentrate was triturated in 1,1'-oxybisethane. The precipitate was filtered off and the filtrate was concentrated, yielding 300 g (91.1%) of 5-[[(1H-pyrrol-2-yl)methylen]amino]pentanoate.

Reference： [1]Patent: US6054468,2000,A

49
[ 140-10-3 ]
[ 29840-56-0 ]
(4-methoxycarbonyl)butyl cinnamamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	Acetyl chloride (5 mL) was added into methanol (150 mL) to prepare hydrogen chloride in methanol solution, and 5-aminopentanoic acid (1 g) was added. The mixture was kept at the room temperature overnight, and evaporated to isolate methyl 5-aminorhoe?tanoate hydrochloride. A mixture of the <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong> (251 mg), cinnamoic acid (74 mg), HBTU (168 mg), diisopropylethylamine (0.87 mL), and dimehylformamide (2 mL) was kept at the room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (20 mL), washed with water twice (10 mL each) followed by brine (10 mL), dried (Na2SO4), and evaporated to isolate (4-methoxycarbonyl)butyl cinnamamide (1, 100 mg). A mixture of (4-methoxycarbonyl)butyl cinnamamide (1, 100 mg), benzaldehyde phenylhydrazone (2, 113 mg), chloramine-T trihydrate (160 mg), and methanol (2 mL) were heated under refluxing for 22 hours. The reaction mixture was diluted with 50% ethyl acetate in n-hexanes (40 mL), filtered, and evaporated. The residue was purified by column chromatography (silica gel 20 g, eluent: 0 to 10% ethyl acetate gradient in hexanes) to isolate methyl 5-(l,3,5-triphenyl-4,5-dihydro-pyrazole-4- carbonyl)aminopentanoate (3, 13 mg) and methyl 5-(l,3,4-triphenyl-4,5-dihydro-pyrazole-5- <n="71"/>carbonyl)aminopentanoate (4, 103 mg). Regiochemistry of each isomer was identified by IH- and 13-C NMR chemical shifts of the CH adjacent to the amide carbonyl. 5-(l,3,5- Triphenyl-4,5-dihydro-pyrazole-4-carbonyl)aminopentanoic acid (5, FN 1-9U) were obtained from 3 by a standard ester hydrolysis condition as shown in the preparation of FN1-2. MS: 464.9 (M+Na), 442.9 (M+H), 325.8, 297.9. 5-(l,3,4-Triphenyl-4,5-dihydro-pyrazole-5- carbonyl)aminopentanoic acid (6, FN1-9S) were obtained from 4 by a similar manner to the preparation of FN1-2. MS: 464.9 (M+Na), 442.9 (M+H), 325.8, 297.9.10270] Assignment of regiochemistry for 5 and 6 is well agreed with their ESI-MS fragmentation: i.e., 5 gives bigger decarbonylation peak (m/z= 297) than 6 because its beta- ketoimino structure facilitates the decarbonylation.[0271] ESI-MS of FN1-9U (upper right panel) and FN1-9S (upper left panel). FN1-9U shows bigger peaks at m/z- 297 than that of FN1-9S, because of the decarbonylated fragment formation (bottom panel).

Reference： [1]Patent: WO2007/67814,2007,A2 .Location in patent: Page/Page column 69-70

50
[ 874100-39-7 ]
[ 29840-56-0 ]
3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-oxo-piperidin-1-ylmethyl)-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With sodium cyanoborohydride; In tetrahydrofuran; at 20 - 60℃; for 49.5h;	Methyl 5-amino-pentanoate hydrochloride {see J. Org. Chem. (1968) 1581} (128 mg, 0.178 mmol) and sodium cyanoborohydride (45 mg, 0.718 mmol) were added to a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (115 mg, 0.239 mmol) obtained in Step F of Example 1 in tetrahydrofuran (anhydrous, 4.0 mL). The mixture was stirred at room temperature for 1.5 hours. Then, the reaction vessel was equipped with a reflux condenser, and the mixture was heated at 60C for 2 days. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 4% methanol/methylene chloride as an eluent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-oxo-piperidin-1-ylmet hyl)-benzamide (Compound H-4, 42.7 mg, 37%) as a white solid. 1H-NMR(CD3OD, 270MHz) delta(PPM) 1.85(4H, m), 2.42(2H, m), 3.40(2H, m) 3.70(2H, dd, J=4.9, 4.3Hz), 3.92(2H, dd, J=4.9, 4.3Hz), 4.65(2H, s), 6.56(1H, td, J=8.9, 4.3Hz), 7.34(1H, m), 7.35(1H, m), 7.45(1H, dd, J=10.7, 2.0Hz) ESI(LC/MS positive mode) m/z 564(M+H)

Reference： [1]Patent: EP1780197,2007,A1 .Location in patent: Page/Page column 141-142

51
[ 1003-29-8 ]
molecular sieves [ No CAS ]
[ 29840-56-0 ]
[ 85504-08-1 ]
[ 137965-52-7 ]

Yield	Reaction Conditions	Operation in experiment
300g (91.1%)	In tricholoromethane; diethyl ether; chloroform;	Step 1 Snythesis of (1-(1H-pyrrol-2-ylmethyl)-2-piperidone. To a stirred solution of 150g of 1H-pyrrol-2-carboxaldehyde in 1500g parts of trichloromethane were added 690, of 5A molecular Sieves. A kit solution of 264, of <strong>[29840-56-0]methyl 5-aminopentanoate hydrochloride</strong> in 1500g of tricholoromethane was added. After stirring for 5 minutes, 465g of thiethylamine were added over 10 minutes. Upon complete addition, the reaction mixture was stirred for 20 hours at ambient temperature. The mixture was filtered over diatomaceous earth and the filtrate was concentrated by evaporation of the solvent. The concentrate was triturated in 1,1'-oxybisethane. The precipitate was filtered off and the filtrate was concentrated, yielding 300g (91.1%) of 5-[[(1H-pyrrol-2-

Reference： [1]Patent: EP832222,2006,B1

52
2-(5-(2,3-dicarbobenzoxy-1-guanidino)-1-oxo-2,3-dihydro-1H-benzo[c]azol-2-yl)acetic acid [ No CAS ]
[ 29840-56-0 ]
[ 1113057-53-6 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2007,vol. 46,p. 1815 - 1832

53
[ 29840-56-0 ]
[ 32909-49-2 ]
[ 917919-73-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 4214 - 4222

54
[ 386703-79-3 ]
[ 29840-56-0 ]
[ 386703-82-8 ]

Reference： [1]European Journal of Inorganic Chemistry,2001,p. 2485 - 2488

55
[RuCl₂(hexamethylbenzene)]2 [ No CAS ]
[ 29840-56-0 ]
[ 56-40-6 ]
[ 386703-82-8 ]

Reference： [1]European Journal of Inorganic Chemistry,2001,p. 2485 - 2488

56
5-(3-tert-butoxycarbonylaminophenyl)isoxazole-3-carboxylic acid [ No CAS ]
[ 29840-56-0 ]
[ 1045792-85-5 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 4370 - 4373

57
5-(4-tert-butoxycarbonylaminophenyl)isoxazole-3-carboxylic acid [ No CAS ]
[ 29840-56-0 ]
[ 1045792-89-9 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 4370 - 4373

58
[ 1002-18-2 ]
[ 29840-56-0 ]
[ 1173531-62-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 460 - 466

59
[ 29840-56-0 ]
[ 2243-83-6 ]
[ 406726-29-2 ]

Reference： [1]European Journal of Medicinal Chemistry,2009,vol. 44,p. 1067 - 1085

60
[ 1144510-31-5 ]
[ 29840-56-0 ]
[ 1144510-36-0 ]

Yield	Reaction Conditions	Operation in experiment
68%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	5-(((5-fluoro-2-oxoindolin-3-ylidene)hydrazono)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (328 mg, 1 mmol) and 8 ml of DMF were stirred at room temperature while 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (394 mg, 2 mmol), hydroxybenzo-triazole (162 mg, 1.2 mmol), triethylamine (404 mg, 4 mmol) and <strong>[29840-56-0]5-aminovaleric acid methyl ester hydrochloride</strong> (202 mg, 1.2 mmol) were added. The mixture was stirred for 24 hours at room temperature. The mixture was diluted with 400 mL of brine. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (300mg, 68% yield) as a red solid. LC-MS (m/z) 442 (M+1).

Reference： [1]Patent: US2009/182029,2009,A1 .Location in patent: Page/Page column 13-14

61
[ 1144510-88-2 ]
[ 29840-56-0 ]
[ 1144510-78-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	3-((5-fluoro-2-oxoindolin-3-ylidene)methyl)benzoic acid (283 mg, 1 mmol) and 8 ml of DMF were stirred at room temperature while 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (394 mg, 2 mmol), hydroxybenzo-triazole (162 mg, 1.2 mmol), triethylamine (404 mg, 4 mmol) and <strong>[29840-56-0]5-aminovaleric acid methyl ester hydrochloride</strong> (202 mg, 1.2 mmol) were added. The mixture was stirred for 24 hours at room temperature. The mixture was diluted with 400 mL of brine. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (337 mg, 89% yield) as a brown solid. LC-MS (m/z) 397 (M+1).

Reference： [1]Patent: US2009/182029,2009,A1 .Location in patent: Page/Page column 29

62
[ 4425-73-4 ]
[ 29840-56-0 ]
[ 1197390-04-7 ]

Yield	Reaction Conditions	Operation in experiment
68%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	Example 5 Preparation of 5-(2-(9H-fluoren-9-ylidene)acetamido)pentanoic acid methyl ester 2-(9H-fluoren-9-ylidene)acetic acid (222 mg, 1 mmol) and 8 ml of DMF were stirred at room temperature while 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (394 mg, 2 mmol), hydroxybenzo-triazole (162 mg, 1.2 mmol), triethylamine (404 mg, 4 mmol) and <strong>[29840-56-0]5-aminovaleric acid methyl ester hydrochloride</strong> (202 mg, 1.2 mmol) were added. The mixture was stirred for 24 hours at room temperature. The mixture was diluted with 400 mL of brine. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (278 mg, 68% yield) as a white solid. LC-MS (m/z) 336 (M+1).

Reference： [1]Patent: US2009/292001,2009,A1 .Location in patent: Page/Page column 10

63
[ 1375557-90-6 ]
[ 29840-56-0 ]
C₃₅H₄₅N₉O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃;	Compound 124:[249] To a solution of acid 123 (87.5 mg, 0.14 mmol) in anhydrous DMF (1 rnL) was added DMAP (21 mg, 0.17 mmol), methyl 5 -amino valerate hydrochloride (26 mg, 0.15 mmol) and EDC (40 mg, 0.21 mmol). The mixture was stirred at room temperature overnight and diluted with ethyl acetate. It was washed with saturated ammonium chloride, brine, saturated sodium bicarbonate and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was striped and the residue was purified through silica gel chromatography (Combiflash, dhchloromethane/MeOH) to give compound 124 (71 mg, y = 70%) as a yel]ow foam. 1H NMR (400 MHz, CDCl3): delta 9.07 (s, IH), 8.62 (s, IH), 8.40 (s, IH), 7.19 (s, IH), 7.17 (s, IH), 7.09 (s, IH), 7.00 (s, IH), 6.74 (s, IH), 6.62 (s, 3H), 6.46 (s, IH), 3.94 (s, 3H), 3.85 (bs, 12H), 3.34-3.31 (m, 2H), 2.32 (t, J = 7.2 MHz, 2H), 1.68-1.55 (m, 4H), 1.48 (s, 9H); MS (ESI, m/z): found 721.0 (M + H) +.

Reference： [1]Patent: WO2010/91150,2010,A1 .Location in patent: Page/Page column 137-138

64
[ 1379588-82-5 ]
[ 29840-56-0 ]
[ 1379588-88-1 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 2694 - 2706

65
[ 1379588-83-6 ]
[ 29840-56-0 ]
[ 1379588-89-2 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 2694 - 2706

66
[ 1379588-84-7 ]
[ 29840-56-0 ]
[ 1379588-90-5 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 2694 - 2706

67
[ 1379588-85-8 ]
[ 29840-56-0 ]
[ 1379588-91-6 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 2694 - 2706

68
[ 1379588-86-9 ]
[ 29840-56-0 ]
[ 1379588-92-7 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 2694 - 2706

69
[ 1379588-87-0 ]
[ 29840-56-0 ]
[ 1379588-93-8 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 2694 - 2706

70
[ 29840-56-0 ]
[ 1392096-50-2 ]