[ CAS No. 101555-60-6 ] {[proInfo.proName]}

Name: 101555-60-6|(R)-2-(1-(tert-Butoxycarbonyl)pyrrolidin-2-yl)acetic acid|95%
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Quality Control of [ 101555-60-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 101555-60-6 ]

CAS No. :	101555-60-6	MDL No. :	MFCD06202402
Formula :	C₁₁H₁₉NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GDWKIRLZWQQMIE-MRVPVSSYSA-N
M.W :	229.27	Pubchem ID :	688606
Synonyms :

Calculated chemistry of [ 101555-60-6 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.82
Num. rotatable bonds :	5
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	63.17
TPSA :	66.84 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) :	-6.87 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.12
Log Po/w (XLOGP3) :	1.16
Log Po/w (WLOGP) :	1.48
Log Po/w (MLOGP) :	1.03
Log Po/w (SILICOS-IT) :	0.6
Consensus Log Po/w :	1.28

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-1.66
Solubility :	4.99 mg/ml ; 0.0218 mol/l
Class :	Very soluble
Log S (Ali) :	-2.16
Solubility :	1.59 mg/ml ; 0.00694 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-0.78
Solubility :	38.0 mg/ml ; 0.166 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.75

Safety of [ 101555-60-6 ]

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

Application In Synthesis of [ 101555-60-6 ]

* 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 [ 101555-60-6 ]
Downstream synthetic route of [ 101555-60-6 ]

[ 101555-60-6 ] Synthesis Path-Upstream 1~6

1
[ 118758-56-8 ]
[ 56502-01-3 ]
[ 101555-60-6 ]

Reference： [1] Tetrahedron Asymmetry, 2004, vol. 15, # 21, p. 3407 - 3412

2
[ 24424-99-5 ]
[ 101555-60-6 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: With sodium hydroxide In water; acetone at 0 - 20℃; Stage #2: With hydrogenchloride In water at 0℃;	(R)-2-Carboxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester: At about 0° C., a 5percent sodium hydroxide solution was added dropwise to a solution of (R)-2-(pyrrolidin-2-yl)acetic acid hydrochloride (3.00 g, 18.18 mmol) in water (30 mL). After diluting the solution with acetone (30 mL), di-tert-butyl dicarbonate (5.94 g, 27.27 mmol) was added dropwise. The resulting mixture was stirred at ambient temperature for about 6 hours and the acetone was removed in vacuo. The pH was adjusted to 3 by adding 3M hydrochloric acid dropwise, at about 0° C. Following standard extractive workup with ethyl acetate, the crude residue was purified by silica gel column chromatography (10percent ethyl acetate in chloroform) to yield the title product as an off-white solid (2.70 g, 65percent). m.p. 98-102° C.; [α]_D²⁰+33.8° (c 2.0, DMF); ¹H NMR (400 MHz, DMSO-d₆) δ 1.37 (s, 3H), 1.60-1.85 (m, 3H), 1.90-2.00 (m, 1H), 2.14-2.27 (m, 1H); 2.54-2.93 (m, 1H), 3.15-3.24 (m, 2H), 3.87-3.95 (m, 1H), 12.13 (s, 1H, exchangeable with deuterium oxide); IR (KBr) υ 3184, 2976, 2882, 1736, 1656, 1421 cm^-1; MS 228 (M-1).

Reference： [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2571 - 2578
[2] Patent: US2009/203763, 2009, A1, . Location in patent: Page/Page column 34

3
[ 152665-79-7 ]
[ 101555-60-6 ]

Reference： [1] Helvetica Chimica Acta, 1999, vol. 82, # 10, p. 1539 - 1558

4
[ 118758-56-8 ]
[ 56502-01-3 ]
[ 101555-60-6 ]

Reference： [1] Tetrahedron Asymmetry, 2004, vol. 15, # 21, p. 3407 - 3412

5
[ 37784-17-1 ]
[ 101555-60-6 ]

Reference： [1] Helvetica Chimica Acta, 1999, vol. 82, # 10, p. 1539 - 1558

6
[ 24424-99-5 ]
[ 61350-65-0 ]
[ 101555-60-6 ]

Reference： [1] European Journal of Medicinal Chemistry, 2011, vol. 46, # 8, p. 3455 - 3461

[ 101555-60-6 ] Synthesis Path-Downstream 1~88

1
[ 101555-60-6 ]
(S)-2-[(S)-3-(1H-Indol-3-yl)-2-((R)-2-pyrrolidin-2-yl-acetylamino)-propionylamino]-3-phenyl-propionamide; hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 2571 - 2578

2
[ 101555-60-6 ]
[(S)-2-((R)-2-[(S)-1-((S)-1-Carbamoyl-2-phenyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethylcarbamoyl]-methyl}-pyrrolidin-1-yl)-1-(4-hydroxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 2571 - 2578

3
[ 101555-60-6 ]
Tyr-D-β-Pro-Trp-Phe-NH2 hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 2571 - 2578

4
[ 37784-17-1 ]
[ 101555-60-6 ]

Reference： [1]Helvetica Chimica Acta,1999,vol. 82,p. 1539 - 1558

5
[ 101555-60-6 ]
[ 59378-81-3 ]

Yield	Reaction Conditions	Operation in experiment
		Scheme 13 : Preparation of 2-(R)-[(2-methyl-3-phenyl-allylamino)-methyl]- pyrrolidin-l-carboxylic acid tert-butyl ester [00197] Experimental condition analogous to Example 22 were used with 2-(R)-[(2-METHYL-3-PHENYL-ALLYLAMINO)-METHYL]-PYRROLIDINE-1-CARBOXYLIC acid tert-butyl ester (prepared according to the scheme 13) were used with 2- (R)-CARBOXYMETHYL-PYRROLIDINE-1-CARBOXYLIC acid tert-butyl ester) 0.5 g (1.51 MMOL), 3,4, 5-trimethoxy benzoic acid 0.38 g (1.8 MMOL), triethylamine 0.1 ML, 1- (DIMETHYLAMINOPROPYL)-3-ETHYLCARBODIIMIDE 0.43 g (2.2 MMOL), and 1- hydroxybenzotriazole 0.2 g (1.5 MMOL) in 10 ml DCM. The reaction yielded 0.46 g of 2- (R) { [2-METHYL-3-PHENYL-ALLYL)-3, 4, 5-trimethoxy-benzoyl)-amino]- METHYL}-PYRROLIDINE-1-CARBOXYLIC acid tert-butyl ester. After BOC deprotection analogous to the Example 13, the compound was transformed to the HCI salt, 0.35 g of a white solid was obtained. Yield : 50% [00198] LC-MSD, m/z for C25H32N204 [M+H] +: 425.4 [00199] H NMR (300 MHz, MeOD) : 8 1.1-1. 4 (m, 1 H), 1.6-1. 9 (m, 3H), 2.0-2. 2 (m, 2 H), 2.2-2. 3 (m, 1 H), 3.2-3. 5 (m, 3 H), 3.5-3. 7 (m, 1 H), 3.7-3. 10 (m, 10 H), 4.1 (s, 3 H), 6.5 (s, 1 H), 7.0 (m, 2 H), 7.2-7. 5 (m, 5 H).

Reference： [1]Patent: WO2004/58705,2004,A2 .Location in patent: Page 57-58

6
[ 101555-60-6 ]
[ 132482-06-5 ]

Yield	Reaction Conditions	Operation in experiment
100%		STEP A: 4-Methylmorfoline (0.240 mL, 2.181 mmol) is added under nitrogen to the solution of (R)-2-(N- Boc-pyrrolidin-2-yl)acetic acid (0.5 g, 2.181 mmol) in anhydrous THF (8 mL). The reaction is cooled with an ice bath and isobuthyl chloroformate (0.283 mL, 2.18 mmol) is added dropwise in 10 min. After 10 min, the white precipitate is filtered off and the solid is washed with anhydrous THF (6 mL). To the solution NaBH4 (0.1 12 g, 2.97 mmol), dissolved in H20 (3 mL), is added dropwise cooling the reaction with an ice bath. The reaction is stirred for 1 h. The organic solvent is evaporated under reduced pressure and the residue is dissolved in EtOAc and washed with 5% citric acid, 5% di NaHC03 and brine. The organic phase is dried over Na2S04, filtered and concentrated under reduced pressure. The crude is purified by flash column chromatography (eluent petroleum ether/EtOAc 7/3) to give the expected compound (0.47 g, 2.18 mmol, Yield: 100%).
90%	With lithium aluminium tetrahydride; In tetrahydrofuran; dichloromethane; at 55℃; for 4h;Inert atmosphere;	Intermediate 5: tert-Butyl (2R)-2-(2-hydroxyethyl)pynOlidine-l-carboxylateTo a mixture of [(2R)-l-(tert-butoxycarbonyl)pyrrolidin-2-yl]acetic acid (2.0 g, 8.7 mmol) in anhydrous DCM (20 mL) lithium aluminum hydride 2.0 M in tetrahydrofurane (6.55 g, 7.23 mL, 13.05 mmol) was added dropwise (under argon), and the reaction mixture was heated to 55C. After stirring for 4 hours (at 55C), the reaction mixture was cooled to room temperature, diluted with AcOEt (20 mL) and treated with saturated NaHC03 (4 mL). Then the solution was concentrated under reduce pressure. To the residue were added DCM. The organic layer was washed with water and brine, and then dried over anhydrous Na2S04, and concentrated under reduced pressure to give title compound (1.68 g, 7.8 mmol, 90%)Light oil C CnH2iN03, MW 215.29, Monoisotopic Mass 215.15, [M+H]+ 216.2. UPLC Rt = 4.69. NMR (300 MHz, CDC13) delta (ppm) 1.41-1.45 (m, 9 H), 1.48-1.64 (m, 7 H), 1.75-1.96 (m, 1 H), 2.20-2.49 (m, 1 H), 3.58-3.71 (m, 1 H), 3.77-3.96 (m, 1 H), 4.29-4.44 (m, 1 H).
90%	With lithium aluminium tetrahydride; In tetrahydrofuran; dichloromethane; at 55℃; for 4h;Inert atmosphere;	General procedure: To a mixture of 2-((2S)-1-tert-butoxycarbonylpyrrolidin-2-yl)acetic acid (2.0g, 8.7mmol) in anhydrous CH2Cl2 (20mL) lithium aluminum hydride 2.0M in THF (7.23mL, 13.05mmol) was added dropwise and the reaction mixture was heated to 55C in inert atmosphere (under argon). After stirring for 4h, the reaction mixture was cooled to room temperature, diluted with AcOEt (20mL) and treated with saturated NaHCO3 (3mL). Then the solution was concentrated under reduce pressure. To the residue were added CH2Cl2 (20mL) and the organic layer was washed with water and brine, and then dried over anhydrous Na2SO4, and concentrated under reduced pressure to give intermediate 6 (1.72g, 8.0mmol) as light oil (yield 91.9%). The same procedure was used for the synthesis of intermediates 7-10.

72%		(R)-2-(2-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester: At about 0 C., N-methylmorpholine (1.16 mL, 10.55 mmol) was added dropwise to a mixture of (R)-2-[1-(tert-butoxycarbonyl)pyrrolidin-2-yl]acetic acid (2.0 g, 8.72 mmol), isobutyl chloroformate (1.36 mL, 10.49 mmol) and tetrahydrofuran (30 mL). After stirring for about 10 min at about 0 C., the mixture was filtered through a pad of Celite. The filtrate was then added to a suspension of sodium borohydride (0.40 g, 10.57 mmol) in tetrahydrofuran (30 mL). The reaction mixture was stirred at about 0 C. for 30 minutes and then at ambient temperature for about 16 hours. Following standard extractive workup with ethyl acetate, the crude residue was purified by silica gel column chromatography (7% ethyl acetate in chloroform) to yield the title compound as an oil (1.35 g, 72%). 1H NMR (400 MHz, DMSO-d6) delta 1.39 (s, 9H), 1.61-2.06 (m, 6H), 3.12-3.28 (m, 2H), 3.35-3.44 (m, 2H), 3.67-3.79 (m, 1H), 4.37 (t, J=5.2 Hz, 1H, exchangeable with deuterium oxide); IR (KBr) upsilon 3425, 2969, 2880, 1681, 1404 cm-1; MS 216 (M+1).
		EXAMPLE 552 2-([2-({2-[(2S)-2-pyrrolidinyl]ethyl}amino)phenyl]sulfonyl}amino)-5,6,7,8-tetrahydro-1-naphthalenecarboxylic acid EXAMPLE 552A tert-butyl(2R)-2-(2-hydroxyethyl)-1-pyrrolidinecarboxylate [0940] A mixture of [(2R)-1-(tert-butoxycarbonyl)-2-pyrrolidinyl]acetic acid (1.004 g, 4.4 mmol) in THF (10 mL) at -10 C. was treated with NMM (0.484 mL, 4.4 mmol) and isopropyl chloroformate (0.572 mL, 4.4 mmol), stirred for 30 minutes, filtered, then added dropwise to a stirred solution of sodium borohydride (0.37 g, 9.8 mmol) in water (4 mL) and stirred for 1 hour. The solution was acidified to pH 4 with 0.1M HCl, then transferred to a separatory funnel and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered, and concentrated to provide the desired product (0.546 g). MS (DCI) m/e 216 (M+H)+.

Reference： [1]Patent: WO2013/64919,2013,A1 .Location in patent: Page/Page column 69
[2]Patent: WO2016/3296,2016,A1 .Location in patent: Page/Page column 21; 22
[3]European Journal of Medicinal Chemistry,2018,vol. 145,p. 790 - 804
[4]Patent: US2009/203763,2009,A1 .Location in patent: Page/Page column 40
[5]Patent: US2004/167128,2004,A1 .Location in patent: Page 106

7
[ 101555-60-6 ]
[ 60307-26-8 ]

Yield	Reaction Conditions	Operation in experiment
82%		(R)-2-(1-Methylpyrrolidin-2-yl)ethanol: At about 0 C., a solution of (R)-2-carboxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.30 g, 5.68 mmol) in dry 1,4-dioxane (10 mL) was added dropwise to a stirred suspension of lithium aluminum hydride (1.08 g, 28.46 mmol) in dry 1,4-dioxane (10 mL). With slow temperature ramping, the mixture was first heated at about 50 C. for about 1 hour, then heated at about 70 C. for about 1 hour, and finally heated at reflux for about 5 hours. After cooling the mixture to about 0 C., cold water was added dropwise until a white granular precipitate was obtained. The precipitate was collected by filtration, washed with ethyl acetate, and the washes were combined with the filtrate. The combined filtrate was concentrated in vacuo to yield the title compound as a brown oil which was used in the next step without further purification (0.600 g, 82%). 1H NMR (400 MHz, DMSO-d6) delta 1.46-1.56 (m, 1H), 1.72-1.84 (m, 3H), 1.87-2.05 (m, 2H), 2.12-2.20 (m, 1H), 2.36 (s, 3H), 2.56-2.63 (m, 1H), 3.03-3.09 (m, 1H), 3.65-3.72 (m, 1H), 3.96-4.03 (m, 1H); IR (KBr) upsilon 3379, 2955, 2789, 1655, 1458 cm-1; MS 130 (M+1).

Reference： [1]Patent: US2009/203763,2009,A1 .Location in patent: Page/Page column 34

8
[ 925922-99-2 ]
[ 101555-60-6 ]
tert-butyl (2R)-2-{2-[(3-{3-cyano-6-[4-fluoro-2-(methoxymethoxy)phenyl]-2-[(furan-2-ylcarbonyl)amino]pyridin-4-yl}phenyl)amino]-2-oxoethyl}pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 5157 - 5171

9
[ 6638-79-5 ]
[ 101555-60-6 ]
[ 1202039-17-5 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 196 - 199
[2]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

10
[ 101555-60-6 ]
[ 1260216-06-5 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 196 - 199

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[ 101555-60-6 ]
[ 1260216-05-4 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 196 - 199

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[ 101555-60-6 ]
[ 1260216-08-7 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 196 - 199

13
[ 101555-60-6 ]
[ 1260216-15-6 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 196 - 199

14
[ 101555-60-6 ]
[ 1260216-17-8 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 196 - 199

15
[ 101555-60-6 ]
[ 1315052-97-1 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 196 - 199

16
[ 626-58-4 ]
[ 101555-60-6 ]
[ 1314696-16-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	General procedure: To a solution of 10 (1 eq.) in DMF (2 ml per mmol of starting material) were added HOBt (1.1 eq.), EDCI (1.1 eq.) and triethylamine (1.6 eq.). The amine (4-methylpiperidine or 1-(2-methoxyphenyl)piperazine, 1.1 eq.) was added last to that mixture. After stirring overnight at room temperature AcOEt was added (15 ml for 1 ml of DMF) and the resulting solution was washed several times with 10% LiCl and brine. The organic layer was dried over MgSO4 and concentred in vacuo to afford the expected product with a satisfactory purity, without further purification.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

17
[ 35386-24-4 ]
[ 101555-60-6 ]
[ 1314696-17-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	General procedure: To a solution of 10 (1 eq.) in DMF (2 ml per mmol of starting material) were added HOBt (1.1 eq.), EDCI (1.1 eq.) and triethylamine (1.6 eq.). The amine (4-methylpiperidine or 1-(2-methoxyphenyl)piperazine, 1.1 eq.) was added last to that mixture. After stirring overnight at room temperature AcOEt was added (15 ml for 1 ml of DMF) and the resulting solution was washed several times with 10% LiCl and brine. The organic layer was dried over MgSO4 and concentred in vacuo to afford the expected product with a satisfactory purity, without further purification.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

18
[ 24424-99-5 ]
[ 61350-65-0 ]
[ 101555-60-6 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

19
[ 101555-60-6 ]
[ 1314696-19-9 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

20
[ 101555-60-6 ]
[ 1314696-20-2 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

21
[ 101555-60-6 ]
[ 1314696-21-3 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

22
[ 101555-60-6 ]
[ 1314696-23-5 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

23
[ 101555-60-6 ]
[ 1314696-26-8 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

24
[ 101555-60-6 ]
[ 1314696-28-0 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

25
[ 101555-60-6 ]
[ 1314696-32-6 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

26
[ 101555-60-6 ]
[ 1314696-33-7 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

27
[ 101555-60-6 ]
[ 1314696-35-9 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

28
[ 101555-60-6 ]
C₁₇H₂₇N₃O [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

29
[ 101555-60-6 ]
[ 1314696-36-0 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

30
[ 101555-60-6 ]
[ 1314696-37-1 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

31
[ 101555-60-6 ]
[ 1314696-40-6 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

32
[ 101555-60-6 ]
[ 1314696-41-7 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

33
[ 101555-60-6 ]
[ 201039-15-8 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

34
[ 101555-60-6 ]
[ 201039-14-7 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3455 - 3461

35
[ 101555-60-6 ]
[ 132482-08-7 ]

Reference： [1]Patent: WO2013/64919,2013,A1

36
[ 101555-60-6 ]
[ 1433607-76-1 ]

Reference： [1]Patent: WO2013/64919,2013,A1

37
[ 101555-60-6 ]
[ 1433607-60-3 ]

Reference： [1]Patent: WO2013/64919,2013,A1

38
[ 101555-60-6 ]
(R)-2-(pyrrolidin-2-yl)acetic acid hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In 1,4-dioxane; at 25℃;	A solution of (R)-2-carboxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester in 2 N hydrogen chloride in dioxane (250 mg, 1 .1 mmol) in 4 N hydrogen chloride in dioxane (2 ml, 8 mmol) was stirred for 2 h at 25C and evaporated to dryness and redissolved in ethanol. After addition of a few drops of 12 M aqueous hydrochloric acid the mixture was stirred at 25C overnight. Solvents were evaporated to give 200 mg (95 %) of (R)-pyrrolidin-2-yl-acetic acid ethyl ester hydrochloride (25 mg, 55 %).

Reference： [1]Patent: WO2013/113860,2013,A1 .Location in patent: Page/Page column 150

39
[ 101555-60-6 ]
[ 916263-26-8 ]

Reference： [1]Patent: WO2016/3296,2016,A1
[2]European Journal of Medicinal Chemistry,2018,vol. 145,p. 790 - 804

40
4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-(piperazin-1-yl)-1,3,5-triazin-2-yl)morpholine [ No CAS ]
[ 101555-60-6 ]
C₃₀H₃₉F₂N₉O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V); N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	General procedure: To a solution of the N-protected amino acid (2 equiv.) inDMF (1 mL) was added HCTU (2 equiv.) followed by DIPEA (4 equiv.). A suspensionof 9 (1 equiv.) in DMF (1 mL) was added and the solution stirred atambient temperature for 1.5 - 2 h. A 5% aqueous NaHCO3 solution(20-30 mL) was added and the resulting suspension stirred vigorously for 15 -30 min. The precipitate was collected, washed with H2O and dried invacuo to give the crude product. (NB: in some cases the reaction mixture wasdried and directly chromatographed or crystallized but this gave inferioryields)

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 4790 - 4794

41
[ 101555-60-6 ]
(7R,8aS)-octahydro-5,5-dimethylindolizin-7-amine [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

42
[ 101555-60-6 ]
(7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine hydrochloride [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

43
[ 101555-60-6 ]
C₁₀H₁₇NO [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

44
[ 101555-60-6 ]
C₁₀H₁₇NO [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

45
[ 101555-60-6 ]
C₁₀H₁₈N₂O [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

46
[ 101555-60-6 ]
(R/S)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

47
[ 101555-60-6 ]
1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-yl-amino)-5-fluoropyrimidin-2-yl-amino)-2-cyclopropyl-4-fluorophenyl)-4-methyl-1H-tetrazol-5-(4H)-one [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

48
[ 101555-60-6 ]
1-(5-(4-((7S,8aR)-octahydro-5,5-dimethylindolizin-7-yl-amino)-5-fluoropyrimidin-2-yl-amino)-2-cyclopropyl-4-fluorophenyl)-4-methyl-1H-tetrazol-5-(4H)-one [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

49
[ 101555-60-6 ]
C₁₅H₂₅NO₃ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

50
[ 101555-60-6 ]
C₁₀H₁₇NO [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

51
[ 101555-60-6 ]
C₁₀H₁₈N₂O [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

52
[ 101555-60-6 ]
C₁₀H₂₀N₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

53
[ 101555-60-6 ]
(S/R)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2953 - 2961

54
8-(2-aminoethoxy)-6-nitro-3,4-dihydroquinolin-2(1H)-one hydrochloride [ No CAS ]
[ 101555-60-6 ]
(R)-tert-butyl 2-(2-((2-((6-nitro-2-oxo-1,2,3,4-tetrahydroquinolin-8-yl)oxy)ethyl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 4386 - 4402

55
[ 101555-60-6 ]
(R)-5-((2-(2-(4-(5-chloro-1H-indol-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethyl)pyrrolidin-1-yl)sulfonyl)quinoline [ No CAS ]