[ CAS No. 172843-97-9 ] {[proInfo.proName]}

Name: 172843-97-9|4-((tert-Butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid|97%
Brand: Ambeed
SKU: A245736
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Quality Control of [ 172843-97-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 172843-97-9 ]

SDS Specification

Alternatived Products of [ 172843-97-9 ]

Product Details of [ 172843-97-9 ]

CAS No. :	172843-97-9	MDL No. :	MFCD02683136
Formula :	C₁₁H₁₉NO₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SPPDKPRJPFTBEV-UHFFFAOYSA-N
M.W :	245.27	Pubchem ID :	1268219
Synonyms :

Calculated chemistry of [ 172843-97-9 ]

Physicochemical Properties

Num. heavy atoms :	17
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.82
Num. rotatable bonds :	5
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	60.29
TPSA :	84.86 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.28 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.71
Log Po/w (XLOGP3) :	0.72
Log Po/w (WLOGP) :	1.14
Log Po/w (MLOGP) :	0.22
Log Po/w (SILICOS-IT) :	0.62
Consensus Log Po/w :	0.88

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.48
Solubility :	8.04 mg/ml ; 0.0328 mol/l
Class :	Very soluble
Log S (Ali) :	-2.08
Solubility :	2.04 mg/ml ; 0.00831 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.33
Solubility :	11.5 mg/ml ; 0.0469 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.69

Safety of [ 172843-97-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 172843-97-9 ]

* 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 [ 172843-97-9 ]
Downstream synthetic route of [ 172843-97-9 ]

[ 172843-97-9 ] Synthesis Path-Upstream 1~6

1
[ 39124-19-1 ]
[ 24424-99-5 ]
[ 172843-97-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: for 48 h; Reflux Stage #2: With sodium hydroxide In 1,4-dioxane; methanol; water at 20℃; for 15 h;	[Step 2] Synthesis of 4-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid: Calcium hydroxide (3.0 g, 41 mmol) was added to an aqueous solution (30 mL) of Reference Example Compound 31 (2.2 g, 13 mmol) at room temperature. The resulting reaction solution was heated to reflux for 48 hours with stirring, and then filtered through Celite, followed by washing of the filtered product with hot water. The filtrate was concentrated under reduced pressure, and the obtained crude product was dissolved in a mixture of water, 1,4-dioxane and methanol (water: 1,4-dioxane:methanol = 10:10:3, 23 mL). Di-tert-butyldicarbonate (3.4 g, 16 mmol) and sodium hydroxide (0.50 g, 13 mmol) were added to the reaction solution at room temperature. The reaction solution was stirred at room temperature for 15 hours, and then concentrated under reduced pressure. Dilute hydrochloric acid (15 mL) was added to the obtained crude product, and extraction was performed with a mixture of chloroform and methanol (chloroform:methanol = 10:1). The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure, to obtain 2.6 g (82percent) of 4-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid (hereinafter referred to as Reference Example Compound 32).

Reference： [1] Patent: EP2832724, 2015, A1, . Location in patent: Paragraph 0181

2
[ 24424-99-5 ]
[ 39124-20-4 ]
[ 172843-97-9 ]

Yield	Reaction Conditions	Operation in experiment
3 g	at 20℃;	To a suspension of dihydro-2H-pyran-4(3H)-one (5.0 g, 50 mmol) and (NH4)2CO3 (24.5 g,255 mmol) in ethanol/water (1:1, 100 mL) was added sodium cyanide (2.5 g, 51 mmol). Thereaction mixture was heated at 50 °C for 12 h and then heated to 80 °C to decompose an excess of (NH4)2CO3. Ethanol was removed and sodium hydroxide (8.16 g, 0.76 mmol) was added. The reaction mixture was refluxed overnight and then cooled to room temperature. The mixture was adjusted to pH=10 with 2 N HCl solution and Boc2O (11.1 g, 51 mmol) andacetonitrile (50 mL) were added. The reaction mixture was stirred overnight at room temperature and ethyl acetate was added. The resulting mixture was adjusted to pH=3-4 with 2 N HCl solution carefully and the organic layer was separated and concentrated. The residue was purified by flash column chromatography on silica gel (DCM/MeOH = 100:1) to afford compound 7 (3.0 g, yield 24percent over three steps) as a white solid.

Reference： [1] Journal of the American Chemical Society, 1997, vol. 119, # 49, p. 11807 - 11816
[2] Patent: WO2015/32945, 2015, A1, . Location in patent: Page/Page column 26; 28

3
[ 29943-42-8 ]
[ 172843-97-9 ]

Reference： [1] Journal of the American Chemical Society, 1997, vol. 119, # 49, p. 11807 - 11816
[2] Patent: EP2832724, 2015, A1,
[3] Patent: WO2015/32945, 2015, A1,
[4] Journal of Organic Chemistry, 2016, vol. 81, # 3, p. 1057 - 1074

4
[ 39124-19-1 ]
[ 172843-97-9 ]

Reference： [1] Journal of the American Chemical Society, 1997, vol. 119, # 49, p. 11807 - 11816
[2] Patent: WO2015/32945, 2015, A1,

5
[ 130312-00-4 ]
[ 172843-97-9 ]

Reference： [1] Journal of Organic Chemistry, 2016, vol. 81, # 3, p. 1057 - 1074

6
[ 66505-81-5 ]
[ 172843-97-9 ]

Reference： [1] Journal of Organic Chemistry, 2016, vol. 81, # 3, p. 1057 - 1074

[ 172843-97-9 ] Synthesis Path-Downstream 1~67

1
[ 949-67-7 ]
[ 172843-97-9 ]
(S)-2-[(4-tert-Butoxycarbonylamino-tetrahydro-pyran-4-carbonyl)-amino]-3-(4-hydroxy-phenyl)-propionic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 5023 - 5030

2
[ 172843-97-9 ]
4-amino-tetrahydropyran-4-carboxylic acid methyl ester hydrochloride [ No CAS ]
[ 199330-67-1 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 11807 - 11816

3
[ 24424-99-5 ]
[ 39124-20-4 ]
[ 172843-97-9 ]

Yield	Reaction Conditions	Operation in experiment
3 g	In acetonitrile; at 20℃;pH 10.0;	To a suspension of dihydro-2H-pyran-4(3H)-one (5.0 g, 50 mmol) and (NH4)2CO3 (24.5 g,255 mmol) in ethanol/water (1:1, 100 mL) was added sodium cyanide (2.5 g, 51 mmol). Thereaction mixture was heated at 50 C for 12 h and then heated to 80 C to decompose an excess of (NH4)2CO3. Ethanol was removed and sodium hydroxide (8.16 g, 0.76 mmol) was added. The reaction mixture was refluxed overnight and then cooled to room temperature. The mixture was adjusted to pH=10 with 2 N HCl solution and Boc2O (11.1 g, 51 mmol) andacetonitrile (50 mL) were added. The reaction mixture was stirred overnight at room temperature and ethyl acetate was added. The resulting mixture was adjusted to pH=3-4 with 2 N HCl solution carefully and the organic layer was separated and concentrated. The residue was purified by flash column chromatography on silica gel (DCM/MeOH = 100:1) to afford compound 7 (3.0 g, yield 24% over three steps) as a white solid.

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 11807 - 11816
[2]Patent: WO2015/32945,2015,A1 .Location in patent: Page/Page column 26; 28

4
[ 172843-97-9 ]
[ 519031-86-8 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2225 - 2239

5
[ 172843-97-9 ]
[ 519031-87-9 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2225 - 2239

6
[ 172843-97-9 ]
[ 519031-88-0 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2225 - 2239

7
[ 172843-97-9 ]
[ 519031-90-4 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2225 - 2239

8
[ 172843-97-9 ]
[ 519031-89-1 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2225 - 2239

9
[ 172843-97-9 ]
2-(4-amino-tetrahydro-pyran-4-yl)-5,6-dihydroxy-pyrimidine-4-carboxylic acid 4-fluoro-benzylamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2225 - 2239

10
[ 172843-97-9 ]
{4-[4-(4-fluoro-benzylcarbamoyl)-5,6-dihydroxy-pyrimidin-2-yl]-tetrahydro-pyran-4-yl}-carbamic acid <i>tert</i>-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2225 - 2239

11
[ 29943-42-8 ]
[ 172843-97-9 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 11807 - 11816
[2]Patent: EP2832724,2015,A1
[3]Patent: WO2015/32945,2015,A1
[4]Journal of Organic Chemistry,2016,vol. 81,p. 1057 - 1074

12
[ 39124-19-1 ]
[ 172843-97-9 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 11807 - 11816
[2]Patent: WO2015/32945,2015,A1

13
[ 172843-97-9 ]
3,12-Dioxa-7,15-diaza-dispiro[5.2.5.2]hexadecane-8,16-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 11807 - 11816

14
[ 172843-97-9 ]
(S)-3-(4-Hydroxy-phenyl)-2-[4-((S)-2-mercapto-3-methyl-butyrylamino)-tetrahydro-pyran-4-carbonyl]-amino}-propionic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 5023 - 5030

15
[ 172843-97-9 ]
[ 169319-45-3 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 5023 - 5030

16
[ 172843-97-9 ]
(S)-2-[(4-Amino-tetrahydro-pyran-4-carbonyl)-amino]-3-(4-hydroxy-phenyl)-propionic acid ethyl ester; hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 5023 - 5030

18
[ 172843-97-9 ]
[ 209919-51-7 ]
[ 675834-02-3 ]

Yield	Reaction Conditions	Operation in experiment
43%	With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; triethylamine; In chloroform; for 26h;Heating / reflux;	4-tert- Butoxycarbonylamino-tetrahydro-pyran-4-carboxylic acid (1.00 g, 4. 08 mmol), 4'- [AMINO-3'-FLUORO-BIPHENYL-2-SULFONIC] acid [TERT-BUTYLAMIDE] (1.31 g, 4.08 [MMOL),] and EEDQ (1.21 g, 4.89 mmol) were dissolved in dry [CHC13] (40 mL). Triethylamine (0.852 mL, 6.12 mmol) was added and the solution heated at reflux for 26 h. The solution was cooled, EtOAc added, and then washed sequentially with 10% aq. citric acid, 1N [NAOH,] water, and brine before drying over [MGS04.] Concentration of the solution under reduced pressure and purification of the crude product by flash chromatography revealed 16a (0.972 g, 43%) as a white foam.

Reference： [1]Patent: WO2004/24679,2004,A1 .Location in patent: Page 79

19
[ 172843-97-9 ]
[ 1029716-09-3 ]

Yield	Reaction Conditions	Operation in experiment
		Ethyl chloroformate (0.234 mL, 0.00245 mol) was added to a solution of 4-[(tert- butoxycarbonyl)amino]tetrahydro-2H-pyran-4-carboxylic acid (0.5 g, 2.0 mmol) and triethylamine (0.341 mL, 2.45 mmol) in THF (6.8 mL) at -10 C. The mixture was stirred at RT for 30 min., filtered, and washed with THF. Sodium tetrahydroborate (0.15 g, 4.1 mmol) in water (1.0 mL) was added to the filtrate at 0 C, and then stirred at RT for 2 h. The reaction mixture was quenched with saturated NH4Cl solution, extracted with EtOAc. The extract was washed with saturated NaHCO3, brine, dried over MgSO4, filtered, and concentrated to give the crude product which was directly used in next step without further purification. LCMS: (M+Na) = 254.1; (M-100+H) = 132.1.
		Part A: (4-Hydroxymethyl-tetrahydro-pyran-4-yl)-carbamic acid tert-butyl esterNeat 4-methylmorpholine (2.7 mL, 24.6 mmol) was added, via syringe, to a rapidly stirred, 0 C, solution of 4-tert-butoxycarbonylamino-tetrahydro-pyran-4- carboxylic acid (5.0 g, 20.4 mmol) and isobutyl chloroformate (3.2 mL, 24.5 mmol) in anhydrous tetrahydrofuran (200 mL) contained in a 1000 mL round bottomed flask. Precipitate immediately formed. The suspension was allowed to stir at 0 C under 2 blanket for 20 minutes then a hand swirled, gas evolving, suspension of sodium borohydride (2.3 g, 61.3 mmol) in methanol (65 mL) was added, at as fast of a rate as possible while maintaining control of the concomitant reaction foaming. When observable gas evolution had ceased the opaque white reaction suspension was transferred to a separatory funnel containing saturated aqueous sodium chloride (500 mL) and extracted with ethyl acetate. Combined organic extracts were dried (MgS04), passed through a plug of silica gel, and evaporated to obtain 4.89 g of off white solid which was used without further purification. LRMS (ESI) m/z 232.2 [(M+H)+, calcd for CnH22N04232.3].

Reference： [1]Patent: WO2008/64157,2008,A1 .Location in patent: Page/Page column 104-105
[2]Patent: WO2011/44212,2011,A1 .Location in patent: Page/Page column 37-38

20
[ 172843-97-9 ]
[ 18107-18-1 ]
[ 885498-48-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	In methanol; hexanes; dichloromethane; at 20℃;	Preparation of methyl 1-(tert-butoxycarbonylamino)cyclohexanecarboxylate; 1-(t-Butoxycarbonylamino)cyclohexanecarboxylic acid (2.5 g, 10.3 mmol) was stirred as a suspension in DCM:MeOH (25 mL, 4:1) at rt and TMSDAM (2 M solution in hexanes (6.5 mL, 13 mmol) was added dropwise. Excess reagent was decomposed with the dropwise addition of AcOH. The reaction was concentrated in-vacuo and the residue purified by Biotage (20% EtOAc/pet ether) to give methyl 1-(tert-butoxycarbonylamino)cyclohexanecarboxylate (2.68 g, 100%).

Reference： [1]Patent: US2009/270394,2009,A1 .Location in patent: Page/Page column 16

21
[ 960080-15-3 ]
[ 172843-97-9 ]
C₄₂H₅₅N₅O₇S [ No CAS ]

Reference： [1]ChemMedChem,2010,vol. 5,p. 65 - 78

22
[ 172843-97-9 ]
[ 97964-72-2 ]
[ 1254318-91-6 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 48h;Product distribution / selectivity;	4-(tert-Butoxycarbonylamino)tetrahydro-2H-pyran-4-carboxylic acid (0.801 g), (5)-2-amino- 3-(4-iodophenyl)propanamide (Example 1, step (ii), 0.947 g) and JV-ethyl-JV-opropylpropan- 2-amine (1.422 mL) were dissolved in DMF (10 mL) and to the solution was added TBTU (1.573 g). The reaction mixture was stirred, at room temperature, for 2 days. The reaction mixture was evaporated to dryness dissolved in dichloromethane (20 mL) and evaporated onto silica. The silica was put on the top of a silica column and eluted with 20% ethyl acetate in ohexane then 50% ethyl acetate in ohexane then 100% ethyl acetate followed by 10% then 20% methanol in ethyl acetate to afford the sub-titled compound (2.00 g).m/e (APCI+) 418.0 [M+2H-BOC]+

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2357 - 2367
[2]Patent: WO2010/128324,2010,A1 .Location in patent: Page/Page column 43-44

23
[ 1254318-97-2 ]
[ 172843-97-9 ]
[ 1254318-98-3 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 48h;	4-(tert-Butoxycarbonylamino)tetrahydro-2H-pyran-4-carboxylic acid (374 mg), (5)-2-amino- 3-(4'-cyanobiphenyl-4-yl)propanamide (Example 3, step (iii), 405 mg) and N-ethyl-N- opropylpropan-2-amine (0.664 mL) were dissolved in DMF (10 mL) and to the solution was added TBTU (734 mg). The reaction mixture was stirred at room temperature for 2 days. The reaction mixture was evaporated to dryness, dissolved in dichloromethane (20 mL) and was absorbed onto silica. The product was purified by chromatography on silica eluting with 20% ethyl acetate in ohexane, then 50% ethyl acetate in ohexane and then 100% ethyl acetate to afford after evaporation of the relevant fractions the sub-titled compound (700 mg).m/e (APCI+) 393 [M+2Eta-BOC]4

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2357 - 2367
[2]Patent: WO2010/128324,2010,A1 .Location in patent: Page/Page column 52

24
[ 172843-97-9 ]
[ 885498-49-7 ]

Reference： [1]Patent: WO2011/44212,2011,A1

25
[ 172843-97-9 ]
[ 1287205-92-8 ]

Reference： [1]Patent: WO2011/44212,2011,A1

26
[ 172843-97-9 ]
(4-[(4-bromophenyl)-(2-pyridin-2-ylcyclopropanecarbonyl)amino]methyl}tetrahydropyran-4-yl)carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: WO2011/44212,2011,A1

27
cis-N-[5-(3,4-dimethylphenyl)piperidin-3-yl]benzenecarboxamide [ No CAS ]
[ 172843-97-9 ]
tert-butyl cis-[4-({3-(3,4-dimethylphenyl)-5-[(phenylcarbonyl)amino]piperidin-1-yl}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With dmap; HATU; In N,N-dimethyl-formamide; at 20℃;	75 mg (0.3 mmol) of <strong>[172843-97-9]4-[(tert-butoxycarbonyl)amino]tetrahydro-2H-pyran-4-carboxylic acid</strong> together with 110 mg (0.3 mmol) of HATU and 47 mg (0.4 mmol) of 4-dimethylaminopyridine were initially charged in 2 ml of DMF, and 60 mg (0.2 mmol) of N-[5-(3,4-dimethylphenyl)piperidin-3-yl]benzamide were added. The reaction mixture was stirred overnight at RT and then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 46 mg (44% of theory)LC-MS (Method 1B): Rt=2.45 min; m/z=536 [M+H]+.

Reference： [1]Patent: US2012/46268,2012,A1 .Location in patent: Page/Page column 28

28
cis-N-[5-(3,4-dimethylphenyl)piperidin-3-yl]benzenecarboxamide [ No CAS ]
[ 172843-97-9 ]
cis-N-{1-[(4-aminotetrahydro-2H-pyran-4-yl)carbonyl]-5-(3,4-dimethylphenyl)piperidin-3-yl}benzenecarboxamide hydrochloride [ No CAS ]

Reference： [1]Patent: US2012/46268,2012,A1

29
[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-ethyl-4-oxo-buten-1-yl]amine trifluoroacetate [ No CAS ]
[ 172843-97-9 ]
1,1-dimethylethyl [4-([(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-ethyl-4-oxo-2-buten-1-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 0 - 20℃;Cooling with ice;	Intermediate 7; 1,1-dimethylethyl [4-([(lS,2JE)-4-(2,3-dihydro-lH-indol-l-yl)-l-ethyl-4- l-yl]amin arbonyl)tetrahydro-2H-pyran-4-yl] car amate; A solution of 50 wt% T3P in EtOAc (1.3 mL, 2.184 mmol) was added dropwise to a solution of [(15',2E)-4-(2,3-dihydro-lH-indol-l-yl)-l-ethyl-4-oxo-2-buten-l-yl]amine trifluoroacetate (500 mg, 1.452 mmol), 4-((tert-butoxycarbonyl)amino)tetrahydro-2H- pyran-4-carboxylic acid (356 mg, 1.452 mmol), and Et3N (1 mL, 7.21 mmol) in CH2CI2 (5 mL) at 0 C (bath temp). The ice bath was removed, and the reaction was stirred at RT. After 1 h 20 min, the reaction mixture was washed with saturated aq. NaHC03 (1 x 5 mL) and 10% citric acid (1 x 5 mL). The organic layer was concentrated under a stream of nitrogen, and the residue was purified by flash column chromatography, giving 251 mg (38%) of the title compound. LC-MS m/z 458 (M+H)+, 0.96 (ret time).

Reference： [1]Patent: WO2012/109415,2012,A1 .Location in patent: Page/Page column 33

30
[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amine trifluoroacetate [ No CAS ]
[ 172843-97-9 ]
1,1-dimethylethyl [4-([(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 0 - 20℃;Cooling with ice;	Intermediate 14; 1,1-dimethylethyl [4-([(lS,2JE)-4-(2,3-dihydro-lH-indol-l-yl)-l-(2-methylpropyl)-4- oxo-2- ten-l-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate; A solution of 50 wt% T3P in EtOAc (1.2 mL, 2.016 mmol) was added dropwise to a solution of [(15',2E)-4-(2,3-dihydro-lH-indol-l-yl)-l-(2-methylpropyl)-4-oxo-2- buten-l-yl] amine trifluoroacetate (500 mg, 1.343 mmol), 4-((tert- butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid (329 mg, 1.343 mmol), and Et3N (0.93 mL, 6.71 mmol) in CH2C12 (5 mL) at 0 C (bath temp). The ice bath was removed, and the reaction was stirred at RT. After 1 h 20 min, the reaction was washed with saturated aq. NaHC03 (1 x 5 mL) and 10% citric acid (1 x 5 mL). The organic layer was concentrated under a stream of nitrogen, and the residue was purified by flash column chromatography, giving 204 mg (31%) of the title compound. LC-MS m/z 486 (M+H)+, 1.07 min (ret time).

Reference： [1]Patent: WO2012/109415,2012,A1 .Location in patent: Page/Page column 36

31
[ 1269407-87-5 ]
[ 172843-97-9 ]
[ 1394001-74-1 ]

Yield	Reaction Conditions	Operation in experiment
67%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 20℃; for 0.416667h;	Intermediate 5; 1,1-dimethylethyl [4-([(3S)-l-(3-cyano-4'-fluoro-4-biphenylyl)-3- pyrrolidinyl] amino} carbonyl)tetrahydro-2H-pyran-4-yl] carbamateHCIA solution of 50 wt% T3P in EtOAc (0.48 mL, 0.806 mmol) was added to a solution of <strong>[172843-97-9]4-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid</strong> (131 mg, 0.535 mmol), 4-[(35)-3-amino- 1 -pyrrolidinyl]-4'-fluoro-3-biphenylcarbonitrilehydrochloride (170 mg, 0.535 mmol), and Et3N (0.22 mL, 1.587 mmol) in CH2C12 (3 mL). The reaction was stirred at RT. After 25 min, CH2C12 (1 mL) and saturated NaHC03 (3 mL) were added. The layers were separated, and the organic layer was washed with 10%> citric acid (3 mL), causing some of the product to precipitate. The precipitate was filtered off and washed with water (1 mL) and CH2C12 (1 mL) and then set aside. The layers of the filtrate were separated, and the organic layer was concentrated under reduced pressure and purified via flash column chromatography. The pure fractions were combined with the precipitate to afford the title compound (183 mg, 67%). LC-MS m/z 509 (M+H)+, 1.14 min (ret time).

Reference： [1]Patent: WO2012/112733,2012,A1 .Location in patent: Page/Page column 26-27

32
[ 100-39-0 ]
[ 172843-97-9 ]
[ 1413936-75-0 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2012,vol. 8,p. 1265 - 1270

33
[ 172843-97-9 ]
[ 557087-61-3 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2012,vol. 8,p. 1265 - 1270

34
[ 172843-97-9 ]
[ 1413936-77-2 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2012,vol. 8,p. 1265 - 1270

35
[ 172843-97-9 ]
[ 1413936-78-3 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2012,vol. 8,p. 1265 - 1270

36
[ 172843-97-9 ]
benzyl 4-(((3R,6R)-3-(3-[(2,3-dihydro-2,2,4,6,7-pentamethyl-2H-1-benzofuran-5-yl)sulfonyl]guanidino)propyl)-6-(4-(tert-butoxycarbonylamino)butyl)-9-((S)-2'-(3-methylbutoxy)-1,1'-binaphth-2-yloxy)-1,4,7-triaza-2,5,8-trioxononan-1-yl)tetrahydro-2H-pyran-4-carboxylate [ No CAS ]

Reference： [1]Beilstein Journal of Organic Chemistry,2012,vol. 8,p. 1265 - 1270

37
[ 172843-97-9 ]
C₅₂H₆₅N₇O₈*2ClH [ No CAS ]

Reference： [1]Beilstein Journal of Organic Chemistry,2012,vol. 8,p. 1265 - 1270

38
[ 172843-97-9 ]
[ 1452228-22-6 ]

Reference： [1]Patent: US2013/225593,2013,A1
[2]Patent: WO2014/127816,2014,A1

39
[ 172843-97-9 ]
C₁₂H₁₅ClN₄O₅ [ No CAS ]

Reference： [1]Patent: US2013/225593,2013,A1
[2]Patent: WO2014/127816,2014,A1

40
[ 172843-97-9 ]
[ 74-88-4 ]
[ 1452228-21-5 ]

Yield	Reaction Conditions	Operation in experiment
		<strong>[172843-97-9]4-(Boc-amino)tetrahydropyran-4-carboxylic acid</strong> (1.96 g, 8.00 mmol) is mixed with N,N-dimethylformamide (15 mL) and sodium hydride (60% in oil, 0.800 g, 20.0 mmol). [0324] Then methyl iodide (1.49 mL, 24.0 mmol) is added and the reaction mixture is stirred for 12 h at room temperature. The precipitate is filtered off. The filtrate is concentrated in vacuo. The residue is extracted with water and EA. The organic phase is dried over magnesium sulfate and concentrated in vacuo to give the product as an oil. MS (ESI+): m/z=274 [M+H]+ HPLC (Method A): Rt=1.13 min
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 12h;	Then methyl iodide (1 .49 mL, 24.0 mmol) is added and the reaction mixture is stirred for 12 h at room temperature. The precipitate is filtered off. The filtrate is concentrated in vacuo. The residue is extracted with water and EA. The organic phase is dried over magnesium sulfate and concentrated in vacuo to give the product as an oil. MS (ESI+): m/z = 274 [M+H]+ HPLC (Method A): Rt = 1 .13 min

Reference： [1]Patent: US2013/225593,2013,A1 .Location in patent: Paragraph 0323-0326
[2]Patent: WO2014/127816,2014,A1 .Location in patent: Page/Page column 69

41
[ 1082954-30-0 ]
[ 172843-97-9 ]
[ 1579996-88-5 ]