[ CAS No. 68327-04-8 ]

Name: 68327-04-8|(1S,2S)-2-Aminocyclopentanol hydrochloride|98%
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Quality Control of [ 68327-04-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 68327-04-8 ]

Product Details of [ 68327-04-8 ]

CAS No. :	68327-04-8	MDL No. :	MFCD07370092
Formula :	C₅H₁₂ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZFSXKSSWYSZPGQ-FHAQVOQBSA-N
M.W :	137.61	Pubchem ID :	16211106
Synonyms :

Calculated chemistry of [ 68327-04-8 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	34.87
TPSA :	46.25 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) :	0.0
Log Po/w (XLOGP3) :	0.38
Log Po/w (WLOGP) :	0.66
Log Po/w (MLOGP) :	0.21
Log Po/w (SILICOS-IT) :	0.14
Consensus Log Po/w :	0.28

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.93
Solubility :	16.1 mg/ml ; 0.117 mol/l
Class :	Very soluble
Log S (Ali) :	-0.92
Solubility :	16.7 mg/ml ; 0.121 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	0.2
Solubility :	220.0 mg/ml ; 1.6 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.79

Safety of [ 68327-04-8 ]

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

Application In Synthesis of [ 68327-04-8 ]

* 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 [ 68327-04-8 ]
Downstream synthetic route of [ 68327-04-8 ]

[ 68327-04-8 ] Synthesis Path-Upstream 1~3

1
[ 221110-46-9 ]
[ 68327-04-8 ]

Reference： [1] Journal of Organic Chemistry, 1997, vol. 62, # 12, p. 4197 - 4199

2
[ 930-45-0 ]
[ 68327-04-8 ]

Reference： [1] Journal of Organic Chemistry, 1997, vol. 62, # 12, p. 4197 - 4199

3
[ 1428988-52-6 ]
[ 68327-04-8 ]

Reference： [1] Patent: US2016/24142, 2016, A1,

[ 68327-04-8 ] Synthesis Path-Downstream 1~56

1
[ 930-45-0 ]
[ 68327-04-8 ]

Reference： [1]Journal of Organic Chemistry,1997,vol. 62,p. 4197 - 4199

2
[ 108-24-7 ]
[ 68327-04-8 ]
[ 137254-02-5 ]

Reference： [1]Journal of Organic Chemistry,1997,vol. 62,p. 4197 - 4199

3
[ 5987-73-5 ]
[ 68327-04-8 ]
N-[(1S,trans)-2-hydroxycyclopentyl]adenosine 2',3',5'-tri-O-acetate [ No CAS ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2000,vol. 43,p. 11 - 28

4
[ 68327-04-8 ]
6-chloro-[8-14C]purineriboside 2',3',5'-tri-O-acetate [ No CAS ]
N-[(1S,trans)-2-hydroxycyclopentyl]-[8-14C]adenosine 2',3',5'-tri-O-acetate [ No CAS ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2000,vol. 43,p. 11 - 28

5
(1R,2R)-2-acetamidocyclopentanol acetate [ No CAS ]
[ 68327-04-8 ]

Reference： [1]Tetrahedron,2000,vol. 56,p. 9773 - 9779

6
[ 141-75-3 ]
[ 68327-04-8 ]
(1S,2S)-N-(2-hydroxycyclopentyl)butyramide [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2004,vol. 2,p. 3329 - 3336

7
[ 68327-04-8 ]
[ 821801-03-0 ]
[ 821801-05-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2004,vol. 2,p. 3329 - 3336

8
[ 221110-46-9 ]
[ 68327-04-8 ]

Reference： [1]Journal of Organic Chemistry,1997,vol. 62,p. 4197 - 4199

9
[ 85-44-9 ]
[ 68327-04-8 ]
2-(2S-Hydroxy-(S)-cyclopentyl)-isoindole-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; sodium methylate; ethyl acetate; toluene;	2-(2S-Hydroxy-(S)-cyclopentyl)-isoindole-1,3-dione (1S,2S)-2-Amino-cyclopentanol hydrochloride (1.20 g) was dissolved in a solution of sodium methoxide (497 mg) in methanol (10 ml), filtered and evaporated in vacuo. The residue was dissolved in toluene (30 ml) and phthalic anhydride (1.55 g) added, and the mixture heated under reflux for 24 h. After cooling, ethyl acetate was added and the mixture filtered. The filtrate was evaporated in vacuo and the residue purified by flash chromatography over silica (40 g) eluding with cyclohexane-ethyl acetate (2:1) to afford the title compound as a colourless solid (1.08 g). Mass spectrum m/z 232 (MH+).

Reference： [1]Patent: US6407076,2002,B1

10
C₂₂H₂₇Cl₂N₈O₃^(1-)*Li⁽¹⁺⁾ [ No CAS ]
[ 68327-04-8 ]
C₂₇H₃₇Cl₂N₉O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With dmap; HATU; In N,N-dimethyl-formamide; at 20℃; for 20h;	Preparative Exampledelta.A round bottomed flask was charged with intermediate E2 (19 mg, 0.036 mmol), 2-hydroxycyclopentalamine hydrochloride (32 mg, 0.233 mmol), HATU (60 mg, 0.158 mmol), DMAP (60 mg, 0.489 mmol), and DMF (2 ml_). The resulting solution was stirred at room temperature for 20 hours, diluted with ethyl acetate (100 ml_), washed with 1.0 M sodium hydroxide aqueous solution, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative TLC on silica gel using 10% methanol in methylene chloride to afford E3 as a white powder (18 mg, 83%). M+H = 606.

Reference： [1]Patent: WO2006/91428,2006,A2 .Location in patent: Page/Page column 115

11
[ 676559-69-6 ]
[ 68327-04-8 ]
(2S,5R)-5-ethynyl-1-{N-((2S)-2-hydroxycyclopentyl)glycyl}pyrrolidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In acetonitrile;	Example 78 (2S,5R)-5-ethynyl-1-{N-((2S)-2-hydroxycyclopentyl) glycyl}pyrrolidine-2-carbonitrile To a stirred solution of (2S,5R)-1-(chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile (0.040 g, 0.20 mmol, Example 8D) in acetonitrile (1 mL) at room temperature was added trans-2-aminocyclopentanol hydrochloride (56 mg, 0.41 mmol) and triethylamine (0.14 ml, 1.02 mmol). The reaction mixture was stirred at room temperature for 18 hours, concentrated under reduced pressure and purified by flash chromatography with 3% methanol:dichloromethane to provide the titled compound. MS (ESI) m/z 262 (M+H)+; 1H NMR (MeOH) 4.79 (m, 1H), 4.17-4.40 (m, 3H), 3.18 (m, 1H), 2.48 (m, 4H); 2.00-2.30 (m, 4H), 1.80 (m, 2H), 1.66 (2H,m).
	With triethylamine; In acetonitrile;	Example 78 (2S,5R)-5-ethynyl-1-{N-((2S)-2-hydroxycyclopentyl) glycyl}pyrrolidine-2-carbonitrile To a stirred solution of (2S,5R)-1-(chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile (0.040 g, 0.20 mmol, Example 8D) in acetonitrile (1 mL) at room temperature was added trans-2-aminocyclopentanol hydrochloride (56 mg, 0.41 mmol) and triethylamine (0.14 mL, 1.02 mmol). The reaction mixture was stirred at room temperature for 18 hours, concentrated under reduced pressure and purified by flash chromatography with 3% methanol:dichloromethane to provide the titled compound. MS (ESI) m/z 262 (M+H)+; 1H NMR (MeOH) 4.79 (m, 1H), 4.17-4.40 (m, 3H), 3.18 (m, 1H), 2.48 (m, 4H); 2.00-2.30 (m, 4H), 1.80 (m, 2H), 1.66 (2H, m).

Reference： [1]Patent: US2004/259843,2004,A1
[2]Patent: US2005/215784,2005,A1

12
[ 1073973-06-4 ]
[ 68327-04-8 ]
[ 1073969-37-5 ]

Yield	Reaction Conditions	Operation in experiment
28%		4-(3-Ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-indazol-1-yl)-2,6-difluoro-benzonitrile (800 mg, 2.43 mmol), <strong>[68327-04-8](1S,2S)-2-hydroxycyclopentylamine hydrochloride</strong> (351 mg, 2.55 mmol) and diisopropylethylamine (471 mg, 3.6 mmol) are combined in DMSO (3 mL) and stirred at 50 C. After 2 h, additional amino alcohol (70 mg) and diisopropylethylamine (120 muL) are added and stirring is continued overnight. The mixture is then treated three times with 10% NaOH in methanol (1 mL) and 30% hydrogen peroxide (0.25 mL) and methanol (1 mL) and heated to 50 C. The reaction mixture is diluted with water (15 mL) and extracted with methylene chloride (2×10 mL). The organic layers are concentrated and purified via chromatography (silica, 0 to 15% methanol in DCM) to give a glass (1.4 g). The glass is re-purified via chromatography (silica, 30 to 100% EtOAc in hexanes over 16 cv), and is triturated with EtOAc and hexanes to give 4-(3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)benzamide (295 mg, 28%) as a crunchy solid. LC/MS: m/z=429 [M+H]+. 1H NMR (400 MHz, d6 DMSO): delta 7.72 (d, 2H), 7.39 (d, 1H), 6.63 (s, 1H), 6.61 (d, 1H), 2.94 (d, 2H), 2.80 (q, 2H), 2.47 (s, 2H), 2.30 (d, 2H), 2.15-2.13 (m, 1H), 1.76-1.35 (m, 5H), 1.18 (t, 3H), 1.01 (s, 3H), 0.99 (s, 3H).

Reference： [1]Patent: US2008/269193,2008,A1 .Location in patent: Page/Page column 48-49

13
[ 68327-04-8 ]
[ 75321-89-0 ]
(+/-)-tert-butyl 3-((2'-[tert-butoxycarbonyl(3''-fluorophenethyl)amino]ethyl)(methyl)amino)-4-([6'-(tert-butoxycarbonylamino)-4'-methylpyridin-2'-yl]methyl)-pyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%		Example 119Synthesis of (1S,2S)-2-(3-flupsilonorophenethylamino)cyclopentanol (XIII-I) trans-(1S, 2S)-2-Aminocyclopentanol hydrochloride (1.51 g, 0.011 mol) and triethylamine (Et3N, 1.32 g, 1.81 g, 0.013 mol), 3 A molecular sieves (3 g) were dissolved in dry DCE (30 mL). The mixture was stirred at room temperature under a N2 atmosphere for 10 min. NaBH(OAc)3 (2.76 g, 0.013 mol) and 1-4 (1.38 g, 0.01 mol) was then added, and the reaction mixture was stirred at room temperature under a N2 atmosphere overnight. NaOH (1 M, 20 mL) was then added, and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (20 mL x 2). The combined organic layers were washed with 1 M NaOH (20 mL) and H2O (20 mL), and then dried over Na2SO4. The solvent was concentrated in vacuo. The residue was purified by column chromatography (silica gel, CH2Cl2 : MeOH = 9.5 : 0.5) to afford a pale-yellow oil (1.38 g, 62%)

Reference： [1]Patent: WO2008/42353,2008,A1 .Location in patent: Page/Page column 75

14
[ 68327-04-8 ]
[ 123843-67-4 ]
[ 1073973-68-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 120℃; for 2h;	4-Bromo-2,6-difluoro-bezonitrile (2.5 g, 1 eq), (<strong>[68327-04-8](1S,2S)-2-aminocyclopentanol hydrochloride</strong> (1.74 g, 1.1 eq), and DIPEA (3.3 mL, 1.1 eq) are dissolved in DMSO (30 mL), and stirred at 120 C. for 2 h. The reaction mixture is poured to saturated aqueous NH4Cl (150 mL), extracted with EtOAc (3×100 mL), dried over Na2SO4, filtered, and concentrated to give 4-bromo-2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)benzonitrile (3.4 g, 100% yield). LCMS: m/z=299, 301 [M+H]+.

Reference： [1]Patent: US2008/269193,2008,A1 .Location in patent: Page/Page column 58

15
[ 67-56-1 ]
[ 1073973-06-4 ]
[ 68327-04-8 ]
[ 1073969-37-5 ]
[ 1073969-71-7 ]

Yield	Reaction Conditions	Operation in experiment
51%; 8%		4-(3-Ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-indazol-1-yl)-2,6-difluoro-benzonitrile (4.55 g, 13.8 mmol), 1(S),2(S)-amino cyclopentanol HCl (2.28 g, 16.6 mmol) and diethylisopropylamine (5.36 g, 41 mmol) were combined in DMSO (25 mL), and stirred at 50 C. After 2 h additional amino alcohol (500 mg) and diethylisopropylamine (2.4 mL) were added and stirring continued for 16 h. The mixture was then treated with 1N NaOH (3 mL) and 30% hydrogen peroxide (1 mL) and heated to 50 C. After 2 h, sodium hydroxide (1 g) and peroxide solution (1 mL) were added followed after 1 h by methanol (10 mL). More sodium hydroxide (1 g) and peroxide solution (1 mL) were added and the temperature boosted to 70 C. for 1 h. The mixture was allowed to cool and partitioned between water (75 mL) and methylene chloride (75 mL). The methylene chloride layer was removed and the aqueous layer washed with more methylene chloride (50 mL). The combined organic layers were combined, concentrated and added to a column with toluene and chromatographed (silica gel, 20 to 100% ethyl acetate in hexanes) to give 2 separated products, a major product (Example 227) and a minor product (Example 220). Minor product: 4-(3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-((1S,2S)-2-hydroxycyclopentylamino)-6-methoxybenzamide (0.49 g, 8%), a white solid. LC/MS m/z=441 [M+H]+. 1H NMR (400 MHz, DMSO): delta 8.10 (d, 1H), 7.67 (br s, 1H), 7.45 (br s, 1H), 6.51 (d, 1H), 6.43 (d, 1H), 4.84 (d, 1H), 3.84 (m, 1H), 3.83 (s, 3H), 3.48, (m, 1H), 2.94 (2 d, 2H), 2.80 (q, 2H), 2.32 (2 d, 2H), 2.14 (m, 1H), 1.67-1.81 (m, 2H), 1.52 (m, 1H), 1.35 (m, 1H), 1.19 (t, 3H), 1.02 (s, 3H), 0.99 (s, 3H). 4-(3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)benzamideThe major product from Example 220 was recrystallized from ethyl acetate in hexanes to provide 4-(3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)benzamide (3.06 g, 51%) as a white solid. LC/MS m/z=429 [M+H]+. 1H NMR (400 MHz, DMSO): delta 0.99 (3H, s), 1.02 (3H, s), 1.18 (3H, t), 1.36 (1H, m), 1.49-1.83 (4H, 4 m), 2.15 (1H, m), 2.32 (2H, 2d), 2.80 (2H, q), 2.95 (2H, 2d), 3.50 (1H, m), 3.84 (1H, m), 4.90 (1H, d), 6.62 (1H, dd, J=2,12 Hz), 6.73 (1H, br m), 7.40 (1H, d J=6 Hz), 7.67 (1H, br s), 7.72 (1H, br s).

Reference： [1]Patent: US2008/269193,2008,A1 .Location in patent: Page/Page column 62-63

16
[ 1073973-05-3 ]
[ 68327-04-8 ]
[ 1073974-02-3 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 60℃; for 4h;	2,6-Difluoro-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (3 g, 9.51 mmol), <strong>[68327-04-8](1S,2S)-2-hydroxycyclopentylamine hydrochloride</strong> (1.96 g, 14.3 mmol), and diisopropylethylamine (2.46 g, 19 mmol) are combined in DMSO (12 mL) and stirred at 60 C. for 4 h to give 2-fluoro-6-((1S,2S)-2-hydroxy-cyclopentylamino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile. The mixture is then diluted with isopropanol (10 mL) and treated three times with 25% aqueous NaOH (1.5 mL) and 30% aqueous hydrogen peroxide (1 mL). The mixture is then partitioned between EtOAc (100 mL) and water (100 mL), and the aqueous layer is washed with additional EtOAc (100 mL). The combined organic layers are concentrated, and the oily residue is purified via chromatography (elution 30 to 100% EtOAc in hexanes). The clean fractions are combined, concentrated and recrystallized from EtOAc/hexanes to give 2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide (3.53 g, 89%) as a white crystalline solid. LCMS m/z=415 [M+H]-. 1H NMR (400 MHz, d6 DMSO): delta 7.72 (br s, 1H), 7.68 (br s, 1H), 7.38 (d, 1H), 6.72 (d, 1H), 6.61 (dd, 1H), 4.91 (d, 1H), 3.84 (m, 1H), 3.50 (m, 1H), 2.94 (2d, 2H), 2.38 (s, 3H), 2.31 (2 d, 2H), 2.15 (m, 1H), 1.57-1.82 (m, 3H), 1.36 (m, 1H), 1.02 (s, 3H), 1.00 (s, 3H).

Reference： [1]Patent: US2008/269193,2008,A1 .Location in patent: Page/Page column 48

17
[ 1073973-06-4 ]
[ 68327-04-8 ]
4-(3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-fluoro-6-(trans-4-hydroxycyclohexylamino)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.1%		4-(3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-fluoro-6-(trans-4-hydroxycyclohexylamino)-benzonitrile (1.5 g, 4.55 mmol) and trans-4-hydroxycyclohexylamine (1.05 g, 9.1 mmol) are combined in DMSO (6 mL) and stirred at 50 C. for 1 h. The mixture is then treated with 10% NaOH in methanol (2 mL) and 30% hydrogen peroxide (0.5 mL) and methanol (2 mL) and heated to 50 C. for 1 h. The reaction mixture is diluted with water (25 mL), extracted with dichloromethane (2×20 mL), and purified via chromatography (silica, 0 to 20% methanol in DCM over 16 cv) to give the product as a glass, which is triturated with EtOAc/hexanes, stirred overnight, filtered off and air dried to give 4-(3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-fluoro-6-(trans-4-hydroxycyclohexylamino)benzamide (1.72 g, 85.1%) as an off-white solid. LC/MS: m/z=443 [M+H]+. 1H NMR (400 MHz, d6 DMSO): delta 7.71 (br s, 1H), 7.65 (br s, 1 h), 7.28 (d, 1H), 6.61 (d, 1H), 6.59 (dd, 1H), 4.56 (d, 1H), 3.45 (m. 1H), 3.31 (m, 1H), 2.94 (s, 2H), 2.80 (s, 2H), 2.32 (s, 2H), 1.96 (m, 2H), 1.80 (m, 2H), 1.31 (m, 2H), 1.20 (m, 2H), 1.18 (t, 3H), 1.00 (s, 6H).

Reference： [1]Patent: US2008/269193,2008,A1 .Location in patent: Page/Page column 49

18
[ 68327-04-8 ]
[ 313279-15-1 ]
C₂₂H₃₇NO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With magnesium sulfate; triethylamine; In dichloromethane; at 20℃; for 3h;	(1S,2S)-2-(N-(4-((triisopropylsilyloxy)methyl)benzyl)pent-4-enamido)cyclopentyl pent-4-enoate (9). A slurry of trans-(1S,2S)-2-Aminocyclopentanol hydrochloride 5 (89.4 mg,0.65 mmol), 4-((triisopropylsilyloxy)methyl)benzaldehyde 6 (146 mg, 0.5 mmol),triethylamine (0.14 mL, 1 mmol) and MgSO4 (100 mg) in 3 mL of dry CH2Cl2 was stirred at room temperature for 3 h. The mixture was filtered through a thin pad of Celite and then the organic solvent was removed under reduced pressure. The residue was dissolved in 5 mL EtOH and NaBH4 (57 mg, 1.5 mmol) was added with stirring at room temperature. After 1 h, the reaction was quenched by water and extracted with ether (20mL x 3). The combined organic phase was washed with brine, dried over Na2SO4. The organic solvent was removed under reduced pressure, and the residue was dissolved in 2.5 mL dry CH2Cl2. 4-Pentenoic acid 8 (153 muL, 1.5 mmol) and N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCI, 288 mg, 1.5 mmol) were added at 0 C with stirring. The reaction mixture was stirred at room temperature overnight. The mixture was then quenched with water, and extracted with EtOAc. The organic layers were washed with saturated aqueous NaHCO3, brine, dried over sodium sulfate, filtered, and evaporated under reduced pressure. The resulting residue was further purified by silica gel chromatography (10% EtOAc in hexane) to give product 9 (229.5 mg, 85% yield, 3:1 of rotamer) as colorless oil. IR (neat, cm-1): 2942, 2865, 1731, 1643, 1462, 1417, 1168, 1093, 995, 912, 881, 804, 681, 659; 1H NMR (500 MHz, CDCl3) delta = 1.09 (d, J=6.8 Hz, 18 H), 1.12 - 1.21 (m, 3 H), 1.57 - 1.76 (m, 4 H), 1.81-1.86 (m, 1H), 2.10-2.20 (m, 1 H), 2.29 - 2.38 (m, 7 H), 2.45-2.70 (m, 1 H), 4.33-4.41 (m, 1 H),4.48 (d, J=17.6 Hz, 18 H), 4.53 (d, J=17.6 Hz, 18 H), 4.72 (d, J=15.6 Hz, 1 H), 4.78 (s,2 H), 4.82 (s, 2 H), 4.91 - 5.05 (m, 4 H), 5.11 (d, J=17.1 Hz, 1 H), 5.24-5.28 (m, 1 H), 5.74-5.82 (m, 2 H), 5.88-5.96 (m, 1 H), 7.13 (d, J=7.8 Hz, 2 H), 7.24 (d, J=7.8 Hz, 2H), 7.32 ppm (d, J=7.8 Hz, 2 H); 13C NMR (126 MHz, CDCl3) delta= 12.00, 18.02, 20.00, 21.73, 27.26, 27.65, 28.77, 29.17, 30.44, 33.37, 33.53, 45.02, 50.03, 63.43, 64.64, 77.43, 115.09, 115.35, 125.73, 125.90, 126.08, 126.30, 136.14, 136.70, 137.45, 140.95, 172.94, 173.19 ppm (* represents signals of minor isomer); HRMS (EI) calcd. for [C32H52NO4Si] (M + H)+ 542.3665, found 542.3679.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 2601 - 2605

19
[ 1310875-94-5 ]
[ 68327-04-8 ]
[ 1310876-01-7 ]

Yield	Reaction Conditions	Operation in experiment
66%		Examples of Synthesis of Carboxamides from Diketoacid Precursor; Representative Example 1; (l S,2S)-4-(5-(2,4-difluorobenzyl)-l -(2-fluorobenzyl)-2-oxo-l,2-dihydropyridin-3-yl)-2- hydroxy-N-(2-hydroxycyclopentyl)-4-oxobut-2-enamide (9).; To a chilled solution of the 4-(l-(2-fluorobenzyl)-5-(4-fluorobenzyl)-2-oxo-l ,2- dihydropyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid 8 (150 mg, 0.338 mmol) indimethyl formamide (DMF) (2.0 mL), was added hydroxybenzotriazole (HOBT) (50 mg, 0.372 mmol), followed by l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDCI-HCl (71 mg, 0.372 mmol). The resulting mixture was stirred for 30 min. A solution of ( l S,2S)-(+)-trans-2-aminocyclopentanol hydrochloride and NaHC03 (31 mg, 0.372 mmol) was added. The resulting mixture was stirred for 2h at 0- 5 C. Thin layer chromatography 05918344(TLC) analysis indicated completion, hence cold water was added to the reaction mixture and then extracted with ethyl acetate (2 x 20 m L). The combined organic phase was separated and washed with water twice, then once with IN HC1 solution, then saturated aqueous NaHCO.? solution. Concentration in vacuo afforded the crude product which was passed through a short plug of silica gel eluting with chloroform, the eluent was concentrated and the residual triturated with hexanes affording the product as a yellow solid in 117 mg (66.0%). The residual solvent was removed in vacuo affording pure product as a yellow solid, mp 60.0- 62.9 C, [a]20D +24.0 (c 0.01, MeOH}. UV (MeOH) 396 nm (epsilon 14,455), 318 nm (epsilon 6327). NMR (CDCI3, 500 MHz): delta 15.33 (bs, IH), 8.16 (d, IH, J= 2.0Hz), 8.08 (s, 111), 7.61-6.85 (m, 9Eta), 5.22 (s, 2Eta), 4.11 (m, IH), 3.94 (m, IH), 3.78 (s, IH), 2.23 (m. III).2.10 (m, IH), 1.88 (m, IH), 1.78 (m, 211).1.59 (m, IH).13C NMR (CDCI3, 125 MHz): delta 181.3, 180.6, 163.4, 163.3, 162.4, 162.1, 162.0, 161.4, 161.3, 160.4, 160.1, 160.0, 159.2, 145.5, 143.9, 142.3, 141.6, 132.4.1 2.4.132.3, 131.5.131.4, 131.3, 131.3, 131.2, 130.7, 130.6, 125.0, 124.9, 124.8, 122.8, 122.7, 122.5, 122.2.122.2, 122.1, 122.1.117.1, 115.9, 115.7, 115.6, 111.9, 111.9, 111.8, 111.7, 104.7, 104.5, 104.3,98.3,79.5,79.3,61.0,60.6,51.5,47.7,47.3, 32.9, 32.8, 32.7, 30.8, 30.7, 30.5, 21.7, 21.5. HRMS (M+H)+ calculated mass 527.1794 for C28H26F3N2O5, found 527.1799.

Reference： [1]Patent: WO2011/71849,2011,A2 .Location in patent: Page/Page column 43-44

20
[ 5909-24-0 ]
[ 68327-04-8 ]
[ 1403863-98-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With N-ethyl-N,N-diisopropylamine; In ethanol; at 60℃; for 15h;	A mixture of ethyl 4-chloro-2-(methylthio)pyrimidine-5- carboxylate (1.4 g, 6.0 mmol), (lS,2S)-2-aminocyclopentanol hydrochloride (0.7 g, 6.9 mmol) and DIEA (1.0 g) in ethanol (20 mL) was heated at 60 C for 15 h. After being cooled to room temperature, the reaction solution was concentrated and the residue was purified on silica gel column (eluting with 0-10% ethyl acetate in petroleum ether) to give ethyl 4-((lS,2S)-2-hydroxycyclopentylamino)-2-(methylthio)pyrimidine-5-carboxylate (1.3 g, 4.37 mmol, yield 73%) as a white solid. MS (ESI): m/z 298.5 [M+l]+.

Reference： [1]Patent: WO2012/145569,2012,A1 .Location in patent: Page/Page column 70

21
(1S,2S)-2-(benzyloxy)cyclopentanamine [ No CAS ]
[ 68327-04-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; under 2068.65 Torr; for 24h;	To a solution of(lS,2S)-2-(benzyloxy)cyclopentanamine (4.5 g, 22 mmol) and hydrochloric acid (0.5 mL) in methanol (100 mL) was added 10 wt.% palladium on activated carbon (500 mg). The mixture was stirred at room temperature under hydrogen atmosphere (40 psi) for 24 h. The catalyst was filtered off and the filtrate was concentrated under reduced pressure to give (lS,2S)-2-aminocyclopentanol hydrochloride as a white solid (2.14 g, 15 mmol, yield 93%).

Reference： [1]Patent: WO2012/145569,2012,A1 .Location in patent: Page/Page column 70

22
[ 1414773-00-4 ]
[ 68327-04-8 ]
[ 1443499-98-6 ]

Yield	Reaction Conditions	Operation in experiment
23%		At 0-5 C 137 mg (1.00 mmol) (1 S,2S)-2-aminocyclopentanol hydrochloride were added to 79.8 mg (2.00 mmol) sodium hydride (60% in mineral oil) in 7 mL anhydrous DMF. After 5 minutes of stirring on the ice bath, 150 mg (0.50 mmol) 6- chloro-3-(4-methoxyfuro[3,2-c]pyridin-2-yl)imidazo[1 ,2-b]pyridazine were added. The ice bath was removed and it was stirred 3 h at room temperature. The reaction mixture was poured into water. It was concentrated. To the residue were added 1 mL DMF, 3 mL methanol und 0.5 mL water. It was heated under reflux and from the hot solution the insoluble material was filtered off using a Whatman filter. The filtrate was concentrated and dissolved in a mixture of 1 mL DMF and 3 mL methanol. The insoluble material was filtered of and discarded. The filtrate was purified by HPLC to afford 43 mg (23%) product. 1H-NMR (300 MHz, DMSO-d6), delta [ppm]= 1.37-1.49 (1H), 1.61 -1.88 (3H), 1.88-2.03 (1H), 2.25-2.38 (1 H), 3.40-3.48 (1 H), 4.01 (3H), 4.96-5.03 (1 H), 6.98 (1H), 7.36 (1H), 7.53 (1H), 8.03 (1 H), 8.10-8.18 (2H). LC-MS (Method 2): Rt = 0.76 min; MS (ESIpos) m/z = 365 [M+H]

Reference： [1]Patent: WO2013/87581,2013,A1 .Location in patent: Page/Page column 98

23
4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid [ No CAS ]
[ 68327-04-8 ]
[ 1445953-99-0 ]

Yield	Reaction Conditions	Operation in experiment
66%		To a chilled solution of 4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-hydroxy-2-oxobut-3-enoic acid (1) (150 mg, 0.338 mmol) in dimethylformamide (DMF) (2.0 mL), was added hydroxybenzotriazole (HOBT) (50 mg, 0.372 mmol), followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI-HCl, 71 mg, 0.372 mmol) and the mixture was stirred for 30 min. A solution of <strong>[68327-04-8](1S,2S)-(+)-trans-2-aminocyclopentanol hydrochloride</strong> and NaHCO3 (31 mg, 0.372 mmol) was added followed by stirring for 2 h at 0-5 C. Cold water was added to the reaction mixture, which was then extracted with ethyl acetate (2 × 20 mL). The combined organic phase was separated, washed with water twice, then once with 1 N HCl solution, and finally with saturated aqueous NaHCO3 solution. Concentration in vacuo afforded the crude product which was passed through a short silica gel column with chloroform as the eluting solvent. The eluent containing the product was concentrated and the resulting residue was triturated with hexanes, which afforded the product as a yellow solid in 117 mg (66%), mp 61-63 C, [alpha]20D[alpha]D20 +41.8 (c 0.01, methanol), UV lambdamax 396 nm (epsilon 14,455, methanol). 1H NMR (CDCl3, 500 MHz): delta 15.33 (br s, 1H), 8.16 (d, 1H, J = 2.0 Hz), 8.08 (s, 1H), 7.61-6.85 (m, 9H), 5.22 (s, 2H), 4.11 (m, 1H), 3.94 (m, 1H), 3.78 (s, 1H), 2.23 (m, 1H), 2.10 (m, 1H), 1.88 (m, 1H), 1.78 (m, 2H), 1.59 (m, 1H). 13C NMR (CDCl3, 125 MHz): delta 181.3, 180.6, 163.4, 163.3, 162.4, 162.1, 162.0, 161.4, 161.3, 160.4, 160.1, 160.0, 159.2, 145.5, 143.9, 142.3, 141.6, 132.4, 132.4, 132.3, 131.5, 131.4, 131.3, 131.3, 131.2, 130.7, 130.6, 125.0, 124.9, 124.8, 122.8, 122.7, 122.5, 122.2, 122.2, 122.1, 122.1, 117.1, 115.9, 115.7, 115.6, 111.9, 111.9, 111.8, 111.7, 104.7, 104.5, 104.3, 98.3, 79.5, 79.3, 61.0, 60.6, 51.5, 47.7, 47.3, 32.9, 32.8, 32.7, 30.8, 30.7, 30.5, 21.7, 21.5. HRMS: calcd for C28H26F3N2O5 (M+H), 527.1794; found 527.1799.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 4112 - 4116

24
[ 68327-04-8 ]
trans-2-(dibenzylamino)cyclopentanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; benzaldehyde; triethylamine; In n-heptane; dichloromethane; ethyl acetate; 1,2-dichloro-ethane;	Step 1. Synthesis of trans-2-(dibenzylamino)cyclopentanol (C10) To a solution of trans-2-aminocyclopentanol hydrochloride (385 mg, 2.82 mmol) in 1,2-dichloroethane was added benzaldehyde (748 mg, 7.04 mmol) and triethylamine (0.51 mL, 3.7 mmol). The mixture was heated to reflux for 2 hours, cooled to room temperature, and sodium triacetoxyborohydride was added. The reaction mixture was heated at reflux for an additional 18 hours, cooled to room temperature, then taken up in dichloromethane. The organic layer was washed with saturated aqueous sodium bicarbonate solution and with water, then dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 25% to 50% ethyl acetate in heptane) afforded the title compound as a golden oil. Yield: 734 mg, 2.61 mmol, 93%. LCMS m/z 282.2 (M+1). 1H NMR (400 MHz, CDCl3) delta 7.35-7.39 (m, 4H), 7.32 (br dd, J=7.8, 7.2 Hz, 4H), 7.21-7.26 (m, 2H), 4.05-4.12 (m, 1H), 3.79 (d, J=13.9 Hz, 2H), 3.52 (d, J=13.9 Hz, 2H), 2.90-2.99 (m, 1H), 1.74-1.95 (m, 2H), 1.52-1.71 (m, 3H), 1.39-1.49 (m, 1H).

Reference： [1]Patent: US2014/88111,2014,A1 .Location in patent: Page/Page column

25
[ 1414772-61-4 ]
[ 68327-04-8 ]
[ 1610454-10-8 ]

Yield	Reaction Conditions	Operation in experiment
16%	With sodium hydrogencarbonate; In butan-1-ol; at 150℃; for 72h;	150 mg (0.56 mmol) 3-(1-benzofur-2-yl)-6-chloroimidazo[1,2-b]pyridazine and 183.7 mg (1.34 mmol) <strong>[68327-04-8](1S,2S)-2-aminocyclopentanol hydrochloride</strong> (1:1) and 186.9 mg (2.23 mmol) sodium hydrogencarbonate in 5.0 mL butan-1-ol were stirred 72 h at 150C. The solvent was removed. The residue was purified by HPLC to yield 29 mg (16%) of the compound. LC-MS (Method 2): Rt = 0.93 min; MS (ESIpos) m/z = 335 [M+H]+. 1H-NMR (300 MHz ,DMSO-d6), delta [ppm]= 1.47-1.91 (5H), 2.18-2.32 (1H), 3.92-4.01 (1H), 4.08-4.15 (1H), 4.78-4.82 (1H), 6.73-6.79 (1H), 7.10-7.16 (1H), 7.20-7.32 (2H), 7.56-7.66 (2H), 7.74-7.82 (2H), 7.88-7.92 (1H).

Reference： [1]Patent: WO2014/76162,2014,A1 .Location in patent: Page/Page column 57

26
2-[5-[(3-cyano-4-fluorophenyl)carbamoyl]-1,2-dimethylpyrrol-3-yl]-2-oxoacetic acid [ No CAS ]
[ 68327-04-8 ]
N-(3-cyano-4-fluorophenyl)-4-[2-[[(1S,2S)-2-hydroxycyclopentyl]amino]-2-oxoacetyl]-1,5-dimethylpyrrole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27.1 mg	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 5h;	Compound 73 : N-(3-cyano-4-fluoro-phenyl)-4-[2-[[ 1 -(hydroxymethyl)cyclopropyl] amino] - 2-oxo-acetyl]- 1 ,5 -dimethyl -pyrrole-2-carboxamide To a vial containing (l-aminocyclopropyl)methanol (32 mg, 0.37 mmol), HATU (128.03 mg, 0.34 mmol) was added followed by 2-[5-[(3-cyano-4-fluoro-phenyl)- carbamoyl]-l,2-dimethyl-pyrrol-3-yl]-2-oxo-acetic acid (120 mg, 0.31 mmol) in DMF (0.48 mL, 6.17 mmol) and DIPEA (0.16 mL, 0.75 g/mL, 0.92 mmol). The resulting mixture was stirred for 5 hours at room temperature. Then water (5 mL) was added and the mixture was extracted using CH2CI2 (2 x 5 mL). The combined organics were concentrated and the mixture purified via preperative HPLC (Stationary phase: RP XBridge Prep C18 OBD- 10muiotaeta,30chi150iotaetaiotaeta, Mobile phase: 0.25% NH4HCO3 solution in water, MeOH) and further by silica gel column chromatography (gradient elution: EtO Ac-heptane 0: 100 to 100:0). The desired fractions were concentrated in vacuo and the residue was dried in a vacuum oven at 55C for 24 hours yielding compound 73 (14 mg). 1H NMR (400 MHz, DMSO-d6) delta ppm 0.67 - 0.81 (m, 4 H), 2.55 (s, 3 H), 3.52 (d, J=4.8 Hz, 2 H), 3.84 (s, 3 H), 4.67 - 4.80 (m, 1 H), 7.52 (t, J=9.2 Hz, 1 H), 7.71 (s, 1 H), 8.02 (ddd, J=9.3, 4.9, 2.8 Hz, 1 H), 8.22 (dd, J=5.8, 2.8 Hz, 1 H), 8.78 (s, 1 H), 10.46 (s, 1 H). LC method B; Rt: 0.80 min. m/z: 397.1 (M-H)" Exact mass: 398.1.

Reference： [1]Patent: WO2015/11281,2015,A1 .Location in patent: Page/Page column 69; 72

27
[ 24424-99-5 ]
[ 68327-04-8 ]
[ 145106-43-0 ]

Yield	Reaction Conditions	Operation in experiment
97.76%	With triethylamine; In methanol; for 22h;	Step 1. To a solution of (lS,2S)-2-aminocyclopentan-l-ol (41-1) HC1 salt (500.00 mg, 3.63 mmol) and triethylamine (1.10 g, 10.89 mmol, 1.51 mL) in MeOH (18.15 mL) was added Boc20 (1.58 g, 7.26 mmol). The reaction was stirred for 22 hour, concentrated under reduced pressure. Flash chromatography (ISCO system, silica (24 g), 0-50% ethyl acetate in hexane) provide 41-2 (714.2 mg, 3.55 mmol, 97.76% yield).
7.21 g	With potassium carbonate; In tetrahydrofuran; water; at 20℃; for 0.75h;	Step 1 tert-Butyl N-(trans-2-hydroxycyclopentyl)carbamate To a tetrahydrofuran-water mixed solution of trans-2-aminocyclopentanol hydrochloride (5.0 g), di-tert-butyl dicarbonate (7.92 g) and potassium carbonate (10 g) were added, and the mixture was stirred at room temperature for 45 minutes. Water was added to the obtained reaction solution, followed by extraction with ethyl acetate. The extract was washed with water and saturated saline in this order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was washed with n-hexane-ethyl acetate to obtain the title compound (7.21 g). 1H-NMR (CDCl3) delta: 1.28-1.40 (2H, m), 1.45 (9H, s), 1.59-1.81 (2H, m), 2.00-2.12 (2H, m), 3.59-3.66 (1H, m), 3.98 (1H, q, J=6.5 Hz), 4.04 (1H, s), 4.70 (1H, br s).
2.87 g	With triethylamine; In methanol; at 0 - 20℃;	Boc2O (3.49 g, 15.98 mmol) was added to a solution, at 0C, of (1S,2S)-2- aminocyclopentan-1-ol-HC1 (2.0 g, 14.53 mmol) and Et3N (4.05 mL, 29.06 mmol) in methanol (20 mL) and stirred. The reaction was allowed to warm to room temperature and after overnight the reaction was concentrated and the crude was purified by column chromatography to give S 13 (2.87 g) as a white solid.

Reference： [1]Patent: WO2017/4342,2017,A1 .Location in patent: Paragraph 0528
[2]Patent: US2015/51190,2015,A1 .Location in patent: Paragraph 0190-0191
[3]Patent: WO2017/192543,2017,A1 .Location in patent: Paragraph 0424; 0425
[4]Journal of Medicinal Chemistry,2019,vol. 62,p. 6015 - 6034

28
[ 1001401-62-2 ]
[ 68327-04-8 ]
N-[(1S,2S)-2-hydroxycyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 18h;	Intermediates 10: N-[(1S,2S)-2-Hydroxycyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide Triethylamine (1.52 ml, 10.90 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (0.59 g, 4.36 mmol) and EDC (0.84 g, 4.36 mmol) were added to a solution of (1R,2S)-2-aminocyclopentan-1-ol hydrochloride (CAS number 137254-03-6; 0.50 g, 3.63 mmol) and 2-(2H-1,2,3-triazol-2-yl)benzoic acid (CAS number 1001401-62-2; 0.76 g, 4.00 mmol) in DCM (10 ml). The reaction was stirred at room temperature for 18 hours and then diluted with DCM (50 ml) and washed with a saturated solution of sodium bicarbonate (2×20 ml). The crude product was purified by column chromatography (silica, 0-100% ethyl acetate/petrol) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) delta ppm 1.36-1.59 (m, 3H), 1.62-1.88 (m, 3H), 3.79-3.93 (m, 1H), 3.94-4.10 (m, 1H), 4.29-4.39 (m, 1H), 7.49-7.58 (m, 1H), 7.58-7.67 (m, 2H), 7.71-7.82 (m, 2H), 8.05 (s, 2H) MS ES+: 273 Intermediates 11: N-[(1S,2S)-2-Hydroxycyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide Prepared according to the procedure for N-[(1S,2S)-2-hydroxycyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Intermediate 10) from 2-(2H-1,2,3-triazol-2-yl)benzoic acid (CAS number 1001401-62-2; 531 mg, 2.81 mmol), <strong>[68327-04-8](1S,2S)-2-aminocyclopentan-1-ol hydrochloride</strong> (CAS number 68327-04-8; 368 mg, 2.67 mmol) and DIPEA (1401 mul, 8.02 mmol) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) delta ppm 1.33-1.48 (m, 2H), 1.49-1.79 (m, 3H), 1.83-1.97 (m, 1H), 3.80-3.88 (m, 1H), 3.89-3.98 (m, 1H), 4.57-4.67 (m, 1H), 7.43-7.55 (m, 2H), 7.56-7.67 (m, 1H), 7.73-7.83 (m, 1H), 8.03 (s, 2H), 8.09-8.23 (m, 1H) MS ES+: 273

Reference： [1]Patent: US2015/232460,2015,A1 .Location in patent: Paragraph 0452-0455; 0456-0459

29
[ 5177-27-5 ]
[ 68327-04-8 ]
C₉H₁₃ClN₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 130℃; for 4h;	To a stirring suspension of 2,4-Dichloro-pyrimidin-5-ylamine (3.03 g, 18.1 mmol) in n- BuOH (40 mL) is added (lS,2S)-2-Amino-cyclopentanol hydrochloride (2.50 g, 17.2 mmol) and DIEA (9.20 ml, 51.8 mmol). The mixture is stirred at 130 C for 4 h. The reaction mixture is then concentrated under reduced pressure and the crude product is triturated to a solid in EtOAc and heptane and filtered to yield BT-1.

Reference： [1]Patent: WO2015/160654,2015,A1 .Location in patent: Page/Page column 150-151

30
methyl 5-(4-(1H-pyrazol-1-yl)benzyl)-2-formyl-4-methylbenzoate [ No CAS ]
[ 68327-04-8 ]
2-((1S,2S)-2-hydroxycyclopentyl)-5-methyl-6-(4-(1H-pyrazol-1-yl)benzyl)isoindolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71 mg		H) 2- ( (IS, 2S) -2-hydroxycyclopentyl) -5-methyl-6- ( 4- ( lH-pyrazol- l-yl)benzyl) isoindolin-l-one A solution of methyl 5- (4- ( lH-pyrazol-l-yl ) benzyl) -2- formyl-4-methylbenzoate (0.16 g) , ( IS, 2S ) -2-aminocyclopentanol hydrochloride (0.06 g) , triethylamine (0.07 mL) and anhydrous magnesium sulfate (0.11 g) in THF (3.10 mL) was stirred at room temperature for 3 hr. The insoluble substance was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was diluted with methanol (3.10 mL) and THF (3.10 mL) , sodium triacetoxyborohydride (0.20 g). was added thereto, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. 5 The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (71 mg) . 1H NMR (300 MHz, DMSO-d6) delta 1.45-1.97 (6H, m) , 2.32 (3H, s) , 4.00-4.28 (4H, m) , 4.40 (2H, s) , 4.90 (1H, d, J = 4.9 Hz), 6.49-6.56 (1H, m) , 7.25 (2H, d, J = 8.5 Hz), 7.41 (2H, d, J = 10 12.8 Hz), 7.67-7.81 (3H, m) , 8.44 (1H, d, J = 2.5 Hz).

Reference： [1]Patent: WO2015/163485,2015,A1 .Location in patent: Paragraph 0356

31
methyl 2-formyl-3,4-dimethyl-5-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)benzoate [ No CAS ]
[ 68327-04-8 ]
2-((1S,2S)-2-hydroxycyclopentyl)-4,5-dimethyl-6-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)isoindolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.04 g		L) 2- ( (IS, 2S) -2-hydroxycyclopentyl) -4, 5-dimethyl-6- (4- imethyl-lH-pyrazol-3-yl) benzyl) isoindolin-l-one A solution of methyl 2-formyl-3 , -dimethyl-5- ( - ( 1- methyl-lH-pyrazol-3-yl) benzyl) benzoate (0.09 g), (lS,2S)-2- aminocyclopentanol hydrochloride (0.03 g) , triethylamine (0.03 mL) and anhydrous magnesium sulfate (0.06 g) in THF (1.80 mL) was stirred at room temperature for 46 hr under nitrogen atmosphere. The insoluble substance was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was diluted with methanol (1.80 mL) and THF (1.80 mL) , sodium . triacetoxyborohydride (0.10 g) was added thereto, and the mixture was stirred at room temperature for 7.5 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.04 g) . XH NMR (300 MHz, DMSO-d6) delta 1.47-1.77 (4H, m) , 1.81-1.97 (2H, m) , 2.20 (3H, s) , 2.23 (3H, s) , 3.86 (3H, s) , 4.07-4.30 (4H, m) , 4.39 (2H, s), 4.89 (1H, d, J = 4.9 Hz), 6.61 (1H, d, J = 2.3 Hz) , 7.12 (2H, d, J = 7.9 Hz), 7.33 (1H, s) , 7.65-7.71 (3H, m) . [0437]

Reference： [1]Patent: WO2015/163485,2015,A1 .Location in patent: Paragraph 0436

32
methyl 5-(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)-2-formyl-3,4-dimethylbenzoate [ No CAS ]
[ 68327-04-8 ]
6-(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)-2-((1S,2S)-2-hydroxycyclopentyl)-4,5-dimethylisoindolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.07 g		H) 6- (2-fluoro-4- ( lH-pyrazol-l-yl ) benzyl ) -2- ( (1S,2S) -2- hydroxycyclopentyl ) -4 , 5-dimethylisoindolin-l-on.e A solution of methyl 5- (2-fluoro-4- ( lH-pyrazol-1- yl) benzyl) -2-formyl-3, 4-dimethylbenzoate (0.17 g) , (lS,2S)-2- aminocyclopentanol hydrochloride (0,06 g) , triethylamine (0.06 mL) and anhydrous magnesium sulfate (0.10 g) in THF (3.40 mL) was stirred at room temperature for 10 hr. The insoluble substance was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was diluted with methanol (3.40 mL) and THF (3.40 mL) , sodium triacetoxyborohydride (0.19 g) was added thereto, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.07 g) . XH NMR (300 MHz, DMSO-d6) delta 1.45-1.60 (1H, m) , 1.62-1.79 (3H, m) , 1.80-1.98 (2H, m) , 2.24 (3H, 's), 2.25 (3H, s), 4.08-4.29 (4H, m),.4.39 (2H, s) , 4.88 (1H, d, J = 4.9 Hz), 6.52-6.58 (1H, m) , 7.15 (1H, t, J = 8.4 Hz), 7.23 (1H, s) , 7.63 (1H, dd, J = 8.3, 2.1 Hz), 7.68-7.77 (2H, m) , 8.52 (1H, d, J = 2.5 Hz).

Reference： [1]Patent: WO2015/163485,2015,A1 .Location in patent: Paragraph 0456

33
[ 1428988-52-6 ]
11β-fluoro-17-(5-fluoropyridin-3-yl)-N-(2-sulphamoylethyl)oestra-1,3,5(10),16-tetraene-3-carboxamide [ No CAS ]
17-(5-fluoropyridin-3-yl)-N-[(1S,2S)-2-hydroxycyclopentyl]oestra-1,3,5⁽¹⁰⁾,16-tetraene-3-carboxamide [ No CAS ]
[ 68327-04-8 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 11 17-(5-fluoropyridin-3-yl)-N-[(1S,2S)-2-hydroxycyclopentyl]oestra-1,3,5(10),16-tetraene-3-carboxamide Analogously to Example 8, 100 mg of 17-(5-fluoropyridin-3-yl)oestra-1,3,5(10),16-tetraene-3-carboxylic acid were reacted with 72 mg of (1S,2S)-2-aminocyclopentan-1-ol hydrochloride (1:1) to give 79 mg of the title compound. C29H33FN2O2 UPLC analysis (Method 1) Rt=1.39 min, mass found ESI(+) 460.25. 1H NMR (300 MHz, DMSO-d6): delta [ppm]=0.99 (s, 3H), 1.32-2.02 (m, 13H), 2.05-2.20 (m, 2H), 2.24-2.43 (m, 3H), 2.50 (br. s., 1H), 2.83-2.93 (m, 2H), 3.25 (s, 1H), 3.89-3.99 (m, 2H), 4.70 (d, 1H), 6.24-6.29 (m, 1H), 7.30 (d, 1H), 7.51-7.60 (m, 2H), 7.67 (dt, 1H), 8.05 (d, 1H), 8.41-8.52 (m, 2H).

Reference： [1]Patent: US2016/24142,2016,A1

34
C₂₄H₁₉ClN₆O [ No CAS ]
[ 68327-04-8 ]
C₂₉H₂₉N₇O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1149 - 1164

35
[ 1351960-86-5 ]
[ 68327-04-8 ]
C₂₃H₂₃FN₆O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1149 - 1164

36
2,6-difluoro-4-(3,6,6-trimethyl-6,7-dihydro-1H-indazol-1-yl)benzonitrile [ No CAS ]
[ 68327-04-8 ]
2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)-4-(3,6,6-trimethyl-6,7-dihydro-1H-indazol-1-yl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 6 (0277) (0278) A stirred solution of trans-<strong>[68327-04-8](1S,2S)-2-aminocyclopentanol hydrochloride</strong> (358 mg, 2.6 mmol) in methanol (5 mL) was treated with DOWEX 550A-OH resin (4 g, freshly washed with methanol), stirred a few minutes, filtered, and the filtrate concentrated in vacuo to a viscous oil free base in a 50 mL round bottom flask. EX-005B (0.599 g, 2.0 mmol) was added, followed by DMSO (1 mL) and Hunig's base (0.4 mL), and the mixture was stirred for 30 min at 90 C. under nitrogen. Water (30 mL) was added, and the suspension stirred a few minutes and filtered and the gummy solid rinsed with water, collected, and air dried overnight. Intermediate EX-006A (2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)-4-(3,6,6-trimethyl-6,7-dihydro-1H-indazol-1-yl)benzonitrile) was dissolved in DMSO (4 mL) and ethanol (4 mL), treated with 1N NaOH (2 mL), then dropwise with 30% hydrogen peroxide (0.31 mL, 3 mmol), and stirred for 30 min at room temperature. Water (50 mL) was added, the mixture stirred a few minutes, then filtered and the solid rinsed with water and air dried overnight. This was dissolved in dichloromethane and added to a silica gel column (70 cc) and eluted with 2:1 DCM/EtOAc, then 1:1 DCM/EtOAc to afford 763 mg (96% for 2 steps) of EX-006B (2-fluoro-6-((1S,2S)-2-hydroxycyclopentylamino)-4-(3,6,6-trimethyl-6,7-dihydro-1H-indazol-1-yl)benzamide) as a white foam. 1H NMR (400 MHz, CDCl3): delta 8.74 (br s, 1H), 6.66 (d, 1H), 6.60 (d, 1H), 6.43 (dd, 1H), 6.16 (d, 1H), 5.55 (br, 1H), 5.38 (d, 1H), 4.07 (m, 1H), 3.62 (br s, 1H), 2.77 (s, 2H), 2.30 (br, 1H), 2.23 (s, 4H), 1.94 (m, 1H), 1.73 (m, 2H), 1.59 (m, 1H), 1.51 (m, 1H), 1.03 (s, 6H).

Reference： [1]Patent: US2016/75662,2016,A1 .Location in patent: Paragraph 0278

37
2-(benzoyloxy)-5-bromo-3-chloro-4-methylbenzoic acid [ No CAS ]
[ 68327-04-8 ]
4-bromo-2-chloro-6-(((1S,2S)-2-hydroxycyclopentyl)carbamoyl)-3-methylphenyl benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.36 g	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 0 - 35℃; for 4h;	To a mixture of 2- (benzoyloxy) -5-bromo-3-chloro-4- methylbenzoic acid (13.2 g) , (IS, 2S) -2-aminocyclopentanol hydrochloride (4.93 g) , triethylamine (16.5 mL) , and DMF (250 mL) was added HATU (15.0 g) at 0C, and the mixture was stirred at room temperature for 4 hr. To the reaction mixture were added ethyl acetate and water at 0C. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (3.36 g).MS: [M+H]+452.0,'454.0

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0389

38
[ 5813-37-6 ]
[ 68327-04-8 ]
4-bromo-1-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-2-naphthamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.69 g	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 0 - 35℃;	To a mixture of 4-bromo-l-hydroxy-2-naphthoic acid (5.00 g) , (IS, 2S) -2-aminocyclopentanol hydrochloride (2.71 g) , HATU (9.25 g) and DMF (30 mL) was added triethylamine (7.83 mL) at 0C, and the mixture was stirred at room temperature overnight. To the reaction mixture was added water, and the mixture was extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under, reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the titlecompound (1.69 g) .MS: [M-H]~347.9, 349.9

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0379

39
C₈H₅BrClFO₂ [ No CAS ]
[ 68327-04-8 ]
5-bromo-3-fluoro-2-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-4-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.59 g	With triethylamine; In tetrahydrofuran; water; at 0℃;	To a suspension of 5-bromo-3-fluoro-2-hydroxy-4- methylbenzoic acid (1 g) in THF (20 mL) was added dropwise a mixture of oxalyl chloride (0.53 mL) and THF (4 mL) at 0C. To the reaction mixture was added one drop of DMF, and the mixture was stirred at 16C for 1.5 hr. The reaction mixture was concentrated under reduced pressure, and the obtained acid chloride residue was dissolved in THF (20 mL) . To a mixture of (IS, 2S) -2-aminocyclopentanol hydrochloride (0.55 g) ,triethylamine (2.80 mL) , THF (20 mL) and water (20 mL) was added dropwise a mixture of the above-mentioned acid chloride and THF. at 0C, and the mixture was stirred at room temperature overnight. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethylacetate/hexane) to give the title compound (0.59 g) .MS: [M+H]+332.0, 334.1

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0336

40
5-bromo-2-hydroxy-3,4-dimethylbenzoic acid [ No CAS ]
[ 68327-04-8 ]
5-bromo-2-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-3,4-dimethylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.18 g	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 10 - 80℃;	A mixture of 5-bromo-2-hydroxy-3, 4-dimethylbenzoic acid (0.52 g) , (IS, 2S) -2-aminocyclopentanol hydrochloride (0.32 g) , HATU (0.97 g), triethylamine (1.48 mL) and DMF (6 mL) was stirred at room temperature overnight, and at 80C for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, andconcentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane ) to give the title compound (0.18 g) .MS: [M+H]+328.0, 330.0

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0348

41
5-bromo-2-hydroxy-3,4-dimethylbenzoic acid [ No CAS ]
[ 68327-04-8 ]
5-bromo-2-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-4-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.38 g		To a suspension of 5-bromo-2-hydroxy-4-methylbenzoic acid (3.06 g) in THF (30 mL) was added dropwise oxalyl chloride (1.74 mL) at 0C. To the reaction mixture was added one drop of DMF, and the mixture was stirred at 16C for 1.5 hr. The reaction mixture was concentrated under reduced pressure, and THF (15 mL) was added to the residue. To a mixture of (1S,2S)- 2-aminocyclopentanol hydrochloride (1.82 g) , triethylamine (9.23 mL) , THF (15 mL) and methanol (10 mL) was added dropwise a mixture of the above-mentioned residue and THF at 0C, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified twice by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.38 g) .1H NMR (300 MHz, DMSO-d6) delta 1.38-1.57 (2H, m) , 1.60-1.76 (2H, m.) , 1.78-1.92 (1H, m) , 1.95-2.10 (1H, m) , 2.30 (3H, s) , 3.93- 4.12 (2H, m) , 4.82 (1H, d, J = 4.3 Hz), 6.91 (1H, s) , 8.15 (1H, s), 8.60 (1H, d, J = 6.6 Hz), 12.75 (1H, s) .

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0359

42
[ 500860-54-8 ]
[ 68327-04-8 ]
(1S,2S)-2-((6-chloro-4,8-bis(methylamino)pyrimido[5,4-d]pyrimidin-2-yl)amino)cyclopentanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In butan-1-ol;	2,6-Dichloro-N,N? -dimethyl-pyrimido [5 ,4-dj pyrimidine-4,8-diamine (88) (300 mg, 1.16 mmol) and <strong>[68327-04-8](1S,2S)-2-aminocyclopentanol hydrochloride</strong> were reacted innbutanol and the crude product was purified by flash column chromatography using gradient elution from CH2C12 / EtOAc (99/1) to CH2C12 / EtOAc (1/4) to afford (1S,2S)-2-((6-chloro- 4, 8-bis(methylamino)pyrimido[5,4-djpyrimidin-2-yl)amino)-cyclopentanol (138) (310 mg,83% yield). 300 MHz ?H NMR (CDC13, ppm): 6-75-6.61 (1H, m) 6.47 (1H, br s) 5.30 (1H, br s) 5.14 (1H, d, J=3.8 Hz) 4. 14-3.95 (2H, m) 3.12 (3H, d, J=5.2 Hz) 3.05 (3H, d, J=5.2 Hz) 2.28-2.02 (2H, m) 1.94-1.61 (3H, m) 1.61-1.43 (1H, m). ESI-MS (m/z): 324, 326 [M+Hf?.

Reference： [1]Patent: WO2017/3822,2017,A1 .Location in patent: Page/Page column 171

43
5,6-dimethyl-4-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)picolinic acid [ No CAS ]
[ 68327-04-8 ]
N-((1S,2S)-2-hydroxycyclopentyl)-5,6-dimethyl-4-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30 mg	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	A mixture of 5,6-dimethyl-4-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)picolinic acid (30.0 mg), <strong>[68327-04-8](1S,2S)-2-aminocyclopentanol hydrochloride</strong> (19.3 mg), WSC (26.8 mg), HOBt (18.9 mg) and triethylamine (28.3 mg) in DMF (1 mL) was stirred at room temperature overnight. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution and extracted twice with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol), and solidified with ethyl acetate-hexane to give the title compound (30.0 mg). 1H NMR (300 MHz, CDCl3) delta1.60-1.96 (4H, m), 2.03-2.18 (1H, m), 2.22 (3H, s), 2.24-2.34 (1H, m), 2.53 (3H, s), 3.94 (3H, s), 3.95-4.03 (1H, m), 4.05 (2H, s), 4.08-4.18 (1H, m), 4.71 (1H, brs), 6.49 (1H, d, J = 1.7 Hz), 7.11 (2H, d, J = 8.0 Hz), 7.36 (1H, d, J = 1.9 Hz), 7.69 (2H, d, J = 8.0 Hz), 7.88 (1H, s), 8.20 (1H, brs).

Reference： [1]Patent: EP3156397,2017,A1 .Location in patent: Paragraph 0339

44
5-methyl-4-[4-(1-methyl-1H-pyrazol-3-yl)benzyl]pyridine-2-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
N-((1S,2S)-2-hydroxycyclopentyl)-5-methyl-4-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
537 mg	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	5-Methyl-4-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)picolinic acid (507 mg), <strong>[68327-04-8](1S,2S)-2-aminocyclopentanol hydrochloride</strong> (454 mg), WSC (632 mg), HOBt (446 mg) and triethylamine (334 mg) were stirred in DMF (20 mL) under a nitrogen atmosphere at room temperature overnight. To the reaction mixture were added water and triethylamine (1 mL), and the mixture was extracted 4 times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) and crystallized from ethyl acetate-hexane to give the title compound (537 mg). 1H NMR (300 MHz, CDCl3) delta 1.61-1.92 (4H, m), 2.04-2.16 (1H, m), 2.18-2.27 (1H, m), 2.29 (3H, s), 3.94 (3H, s), 3.96-4.02 (1H, m), 4.04 (2H, s), 4.07-4.18 (1H, m), 4.60 (1H, d, J = 1.5 Hz), 6.50 (1H, d, J = 2.3 Hz), 7.13 (2H, d, J = 8.1 Hz), 7.36 (1H, d, J = 2.3 Hz), 7.70 (2H, d, J = 8.1 Hz), 8.00 (1H, s), 8.11 (1H, d, J = 3.0 Hz), 8.28 (1H, s).

Reference： [1]Patent: EP3156397,2017,A1 .Location in patent: Paragraph 0271

45
6-(4-chlorophenyl)-2-(3-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
6-(4-chlorophenyl)-2-(3-fluorophenyl)-N-[(1S,2S)-2-hydroxycyclopentyl]-3-oxo-2,3-dihydropyridazine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49 mg	With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 14h;	A solution of 75 mg intermediate 17, 60 mg trans-(1 S,2S)-2-aminocyclopentanol hydrochloride (1 :1 ), 165.5 mg HATU, 0.1 1 mL ethyldiisopropylamine and 1 .3 mg 4-dimethylaminopyridine in 2 mL of DMF was stirred at room temperature for 14 hours. Then the reaction mixture was filtered and subjected to RP-HPLC (Instrument: Labomatic HD-3000 HPLC gradient pump, Labomatic Labocol Vario-2000 fraction collector; column: Chromatorex C-18 125 mm x 30 mm, eluent A: 0.1 % formic acid in water, eluent B: acetonitrile; gradient: A 60% / B 40%? A 20% / B 80%; flow: 150 mL/min; UV-detection: 254 nm) to yield 49 mg 6-(4-chlorophenyl)-2-(3- fluorophenyl)-N-[(1 S,2S)-2-hydroxycyclopentyl]-3-oxo-2,3-dihydropyridazine-4-carboxamide. 1H NMR (400 MHz, DMSO-d6) delta ppm = 1.37 - 1 .55 (m, 2 H), 1.57 - 1 .76 (m, 2 H), 1.77 - 1 .89 (m, 1 H), 2.03 - 2.15 (m, 1 H), 3.89 - 3.97 (m, 1 H), 3.97 - 4.07 (m, 1 H), 4.94 (d, 1 H), 7.33 - 7.42 (m, 1 H), 7.51 - 7.67 (m, 5 H), 7.95 - 8.04 (m, 2 H), 8.63 (s, 1 H), 9.34 (d, 1 H).

Reference： [1]Patent: WO2017/202816,2017,A1 .Location in patent: Page/Page column 164; 165

46
6-(4-chlorophenyl)-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
6-(4-chlorophenyl)-N-[(1S,2S)-2-hydroxycyclopentyl]-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3 mg	With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 14h;	A solution of 128 mg intermediate 6-(4-chlorophenyl)-2-(1 -methyl-i H-pyrazol-4-yl)-3-oxo-2,3- dihydropyridazine-4-carboxylic acid (46%), 50 mg (1 S,2S)-2-aminocyclopentanol hydrochloride (1:1), 135 mg HATU, 0.13 mL ethyldiisopropylamine and 1 mg 4-dimethylaminopyridine in 1 mL of DMF was stirred at room temperature for 14 hours. Then the reaction mixture wasfiltered and subjected to RP-HPLC (instrument: Labomatic HD-3000 HPLC gradient pump, Labomatic Labocol Vario-2000 fraction collector; column: Chromatorex 0-18 125 mm x 30 mm, eluent A: 0.ivol% formic acid in water, eluent B: acetonitrile; gradient: A 70% I B 30% - A 30% I B 70%; flow: 150 mLlmin; UV-detection: 254 nm) to yield 3 mg 6-(4-chlorophenyl)-N- [(1 S ,2S)-2-hyd roxycyclopentyl]-2-(i -methyl-i H-pyrazol-4-yl)-3-oxo-2 ,3-d ihyd ropyridazine-4-carboxamide.1H NMR (400 MHz, DMSO-d6) 6 [ppm] = 1.38- 1.58 (m, 2 H), 1.60- 1.79 (m, 2 H), 1.80- 1.89(m, 1 H), 2.03 -2.18 (m, 1 H), 3.93 (s, 3 H), 3.94 - 3.99 (m, 1 H), 3.99 -4.07 (m, 1 H), 4.97 (d,1 H), 7.55 - 7.65 (m, 2 H), 8.07 - 8.14 (m, 3 H), 8.52 - 8.60 (m, 2 H), 9.44 (d, 1 H).

Reference： [1]Patent: WO2018/146010,2018,A1 .Location in patent: Page/Page column 181

47
6-(4-chlorophenyl)-3-oxo-2-(pyridin-3-yl)-2,3-dihydropyridazine-4-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
6-(4-chlorophenyl)-N-[(1S,2S)-2-hydroxycyclopentyl]-3-oxo-2-(pyridin-3-yl)-2,3-dihydropyridazine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31 mg	With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 14h;	A solution of 75 mg intermediate 6-(4-chlorophenyl)-3-oxo-2-(pyridin-3-yl)-2,3-dihydropyridazine-4-carboxylic acid, 62 mg (1 S,2S)-2-aminocyclopentanol hydrochloride (1:1),174 mg HATU, 0.16 mL ethyldiisopropylamine and 1 mg 4-dimethylaminopyridine in 2 mL ofDMF was stirred at room temperature for 14 hours. Then the reaction mixture was filtered andsubjected to RP-HPLC (instrument: Labomatic HD-3000 HPLC gradient pump, LabomaticLabocol Vario-2000 fraction collector; column: Chromatorex 0-18 125 mm x 30 mm, eluent A:0.lvol% formic acid in water, eluent B: acetonitrile; gradient: A 70% I B 30% - A 30% I B70%; flow: 150 mLlmin; UV-detection: 254 nm) to yield 31 mg 6-(4-chlorophenyl)-N-[(1S,2S)-2-hydroxycyclopentyl]-3-oxo-2-(pyridin-3-yl)-2,3-d ihyd ropyridazine-4-carboxamide.1H NMR (400 MHz, DMSO-d6) 6 [ppm] = 1.39-1.55 (m, 2 H), 1.58-1.76 (m, 2 H), 1.77-1.88(m, 1 H), 2.03 -2.14 (m, 1 H), 3.90 - 3.96 (m, 1 H), 3.98 - 4.06 (m, 1 H), 4.94 (d, 1 H), 7.56 -7.61 (m, 2 H), 7.63 (dd, 1 H), 7.98-8.03 (m, 2 H), 8.16 (ddd, 1 H), 8.65 (s, 1 H), 8.69 (dd, 1 H),8.91 (d, 1 H), 9.31 (d, 1 H).[ct]D2 = +34.5 (c = 1.00, DMSO).

Reference： [1]Patent: WO2018/146010,2018,A1 .Location in patent: Page/Page column 240

48
3-oxo-2-(pyridin-3-yl)-6-[4-(trifluoromethyl)phenyl]-2,3-dihydropyridazine-4-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
N-[(1S,2S)-2-hydroxycyclopentyl]-3-oxo-2-(pyridin-3-yl)-6-[4-(trifluoromethyl)phenyl]-2,3-dihydropyridazine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	3-Oxo-2-(pyridin-3-yl)-6-[4-(trifluoromethyl)phenyl]-2 ,3-di hydropyridazi ne-4-carboxylic acid (50mg, 0.138 mmol) was dissolved in anhydrous DMF (1.05 mL). (1S,2S)-2-Aminocyclopentanolhydrochloride (1:1) (38 mg, 0.28 mmol), N-ethyl-N-isopropylpropan-2-amine (157 pL, 0.90 mmol), and propane phosphonic acid anhydride (T3P, 122 pL, 50% in DMF, 208 pmol) were successively added. It was stirred for 2 h at rt. The reaction mixture was diluted with methanol and concentrated under vacuum. The residue was purified by RP-HPLC (column: X-Bridge018 5pm lOOx3Omm, mobile phase: (water + 0.2 vol% aqueous ammonia (32%)) acetonitrile, gradient) to afford 22.2 mg (36%) of the title compound.1H-NMR (400MHz, DMSO-d6): 6 [ppm] = 1.41 - 1.56 (m, 2H), 1.57- 1.87 (m, 3H), 2.04-2.14 (m, 1H), 3.94 (quin, 1H), 3.99 -4.07 (m, 1H), 4.95 (d, 1H), 7.64 (dd, 1H), 7.89 (d, 2H), 8.17(ddd, 1 H), 8.21 (d, 2H), 8.69 - 8.73 (m, 2H), 8.92 (d, 1 H), 9.29 (d, 1 H).= +40.1 (c = 1.00, methanol).

Reference： [1]Patent: WO2018/146010,2018,A1 .Location in patent: Page/Page column 220; 221

49
6-[4-(difluoromethyl)phenyl]-3-oxo-2-(pyridin-3-yl)-2,3-dihydropyridazine-4-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
6-[4-(difluoromethyl)phenyl]-N-[(1S,2S)-2-hydroxycyclopentyl]-3-oxo-2-(pyridin-3-yl)-2,3-dihydropyridazine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13 mg	With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 14h;	A solution of 65 mg intermediate 6-[4-(d ifluoromethyl )phenyl]-3-oxo-2-(pyrid in-3-yl)-2,3-dihydropyridazine-4-carboxylic acid, 60 mg (1 S,2S)-2-aminocyclopentanol hydrochloride (1:1),144 mg HATU, 0.1 mL ethyldiisopropylamine and 1 mg 4-dimethylaminopyridine in 2 mL ofDMF was stirred at room temperature for 14 hours. Then the reaction mixture was filtered andsubjected to RP-HPLC (instrument: Labomatic HD-3000 HPLC gradient pump, LabomaticLabocol Vario-2000 fraction collector; column: Chromatorex 0-18 125 mm x 30 mm, eluent A:0.lvol% formic acid in water, eluent B: acetonitrile; gradient: A 85% B 15% - A 45%/B55%; flow: 150 mL/min; UV-detection: 254 nm) to yield 13 mg 6-[4-(difluoromethyl)phenyl]-N-[(1 S ,2S)-2-hyd roxycyclopentyl]-3-oxo-2-(pyridin-3-yl)-2 ,3-d ihyd ropyridazine-4-carboxamide.1H NMR (400 MHz, DMSO-d6) 6 [ppm] = 1.39-1.56 (m, 2 H), 1.58-1.76 (m, 2 H), 1.77-1.87(m, 1 H), 2.04 -2.14 (m, 1 H), 3.94 (br d, 1 H), 3.98-4.07 (m, 1 H), 4.95 (br d, 1 H), 7.13 (t, 1H), 7.64 (dd, 1 H), 7.72 (d, 2 H), 8.13 (d, 2 H), 8.15-8.20 (m, 1 H), 8.66-8.72 (m, 2 H), 8.92(d, 1 H), 9.31 (d, 1 H).

Reference： [1]Patent: WO2018/146010,2018,A1 .Location in patent: Page/Page column 247

50
3-(4-chlorophenyl)-6-oxo-6H-1,4’-bipyridazine-5-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
3-(4-chlorophenyl)-N-[(1S,2S)-2-hydroxycyclopentyl]-6-oxo-6H-1,4’-bipyridazine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14 mg	With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 14h;	A solution of 65 mg intermediate 3-(4-chlorophenyl)-6-oxo-6 H-i ,4?-bi pyridazine-5-carboxylic acid, 54 mg (1S,2S)-2-aminocyclopentanol hydrochlorid (1:1), 150 mg HATU, 0.14 mL ethyldiisopropylamine and 1 mg 4-dimethylaminopyridine in 2 mL of DMF was stirred at room temperature for 14 hours. Then the reaction mixture was filtered and subjected to RP-HPLC(instrument: Labomatic HD-3000 HPLC gradient pump, Labomatic Labocol Vario-2000 fraction collector; column: Chromatorex 0-18 125mm x 30mm, eluentA: 0.lvol% formic acid in water, eluent B: acetonitrile; gradient: A 85% I B 15% - A 45% I B 55%; flow: 150 mLlmin; UVdetection: 254 n m) to yield 14 mg 3-(4-chlorophenyl)-N-[(1 S ,2S)-2-hyd roxycyclopentyl]-6-oxo- 6H-1 ,4?-bipyridazine-S-carboxamide.1H NMR (400 MHz, DMSO-d6) 6 [ppm] = 1.41 - 1.57 (m, 2 H), 1.60- 1.76 (m, 2 H), 1.79- 1.88(m, 1 H), 2.07 - 2.14 (m, 1 H), 3.90 - 3.98 (m, 1 H), 3.98 - 4.06 (m, 1 H), 4.95 (d, 1 H), 7.59 -7.64 (m, 2 H), 8.05-8.11 (m, 2 H), 8.22 (dd, 1 H), 8.63 (s, 1 H), 9.10 (d, 1 H), 9.48 (dd, 1 H),9.75 (dd, 1 H).

Reference： [1]Patent: WO2018/146010,2018,A1 .Location in patent: Page/Page column 270; 271

51
6-[6-(difluoromethyl)pyridin-3-yl]-3-oxo-2-(pyridin-3-yl)-2,3-dihydropyridazine-4-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
6-[6-(difluoromethyl)pyridin-3-yl]-N-[(1S,2S)-2-hydroxycyclopentyl]-3-oxo-2-(pyridin-3-yl)-2,3-dihydropyridazine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54 mg	With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 14h;	A solution of 75 mg intermediate 6-[6-(d ifluoromethyl)pyrid in-3-yl]-3-oxo-2-(pyrid in-3-yl)-2,3-dihydropyridazine-4-carboxylic acid, 60 mg (1 S,2S)-2-aminocyclopentanol hydrochloride (1:1),166 mg HATU, 0.15 mL ethyldiisopropylamine and 1 mg 4-dimethylaminopyridine in 2 mL ofDMF was stirred at rt for 14 hours. Then the reaction mixture was filtered and subjected toRP-HPLC (instrument: Labomatic HD-3000 HPLC gradient pump, Labomatic Labocol Vario2000 fraction collector; column: Chromatorex 0-18 125 mm x 30 mm, eluent A: 0.lvol% formic acid in water, eluent B: acetonitrile; gradient: A 85% I B 15% - A 45% I B 55%; flow: 150 mLlmin; UV-detection: 254 nm) to yield 54 mg 6-[6-(difluoromethyl)pyridin-3-yl]-N-[(1S,2S)-2- hydroxycyclopentyl]-3-oxo-2-(pyridin-3-yl)-2,3-d ihyd ropyridazine-4-carboxamide.1H NMR (400 MHz, DMSO-d6) 6 [ppm] = 1.39- 1.56 (m, 2 H), 1.58- 1.67 (m, 1 H), 1.67- 1.76(m, 1 H), 1.77- 1.87 (m, 1 H), 2.03-2.15 (m, 1 H), 3.94 (quin, 1 H), 3.98-4.07 (m, 1 H), 4.95(d, 1 H), 7.06 (t, 1 H), 7.62 - 7.67 (m, 1 H), 7.84 (d, 1 H), 8.19 (ddd, 1 H), 8.58 (dd, 1 H), 8.70(dd, 1 H), 8.76 (s, 1 H), 8.94 (d, 1 H), 9.24 - 9.29 (m, 2 H).

Reference： [1]Patent: WO2018/146010,2018,A1 .Location in patent: Page/Page column 264; 265

52
6-((3-(5-methylisoxazol-3-yl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yloxy)methyl)nicotinic acid [ No CAS ]
[ 68327-04-8 ]
N-((1S,2S)-2-hydroxycyclopentyl)-6-(((3-(5-methylisoxazol-3-yl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)oxy)methyl)nicotinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65.8%		General procedure: A DMF solution (5 mL) containing HOBt (68 mg, 0.496 mmol), EDCI (95 mg, 0.496 mmol), and A4 (100 mg, 0.248 mmol) was stirred at room temperature for 10 mins under Ar. 4-aminomorpholine () (30.6 mg, 0.3 mmol) and DIPEA (130 mg, 0.992 mmol) were added to the reaction mixture successively. The mixture was stirred at RT for 12h. TLC (DCM: MeOH =10:1, Rf=0.4) showed the starting material was consumed completely. DCM (25 mL) was added to the reaction mixture and then the resulting mixture was poured into 30 mL water, and adjusted to pH 5?6 with aqueous citric acid (2N). The organic layer was separated and washed with water (20mL*2), dried over anhydrous Na2SO4, and concentrated. The residue was purified by preparative TLC to give product (36 mg, 29.7%) as a white solid. 1H NMR (400MHz, DMSO-d6) delta: 9.76 (s, 1H),8.99 (s, 1H), 8.61?8.60 (d, 1H), 8.59 (d, 1H), 8.38?8.36 (m, 2H), 8.23?7.85 (m, 2H), 6.93 (s, 1H), 5.78 (s, 2H), 3.68 (s, 4H), 2.90 (s, 4H), 2.58 (s, 3H); LC-MS: m/z (ES+) for C24H22N8O4 487.15 [M+1]+.

Reference： [1]Patent: EP3388433,2018,A1 .Location in patent: Paragraph 0151; 0154; 0156

53
6-(((3-(5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)isoxazol-3-yl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)oxy)methyl)nicotinic acid [ No CAS ]
[ 68327-04-8 ]
C₃₀H₃₁N₇O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: A DMF solution (5 mL) containing HOBt (54 mg), EDCI (76.7 mg), and D7 (105 mg) was stirred at roomtemperature for 10 mins under N2. Morpholin-4-ylamine (49mg) (CAS: 4319-49-7) and DIPEA (130mg) were added tothe reaction mixture by turn. The mixture was stirred at RT for 60h. TLC (DCM: MeOH=20:1, Rf=0.3) showed the startingmaterial was consumed completely.To the reaction mixture were added DCM (25 mL) and 30 mL water. The organiclayer was washed with water (20mL*2), dried over anhydrous Na2SO4, and concentrated under reduced pressure. Theresidue was purified by silica gel column to give product Da (76.4 mg, 65%) as white solid.

Reference： [1]Patent: EP3388433,2018,A1 .Location in patent: Paragraph 0211; 0212; 0216; 0217

54
[ 85-44-9 ]
[ 68327-04-8 ]
[ 223761-82-8 ]

Yield	Reaction Conditions	Operation in experiment
73.5%		Trans-(1S,2S)-2-Aminocyclopentanol hydrochloride 15-1(CAS: 68327-04-8) (1.37 g, 10 mmol) and Et3N (3 g,30 mmol) were added to 40 mL of toluene and stirred at RT for 5 mins. Then phthalic anhydride (1.48 g, 10 mmol) wasadded under stirring and the reaction mixture was refluxed under stirring for 4 h. TLC showed the reaction was completed.After cooled to r. t., the reaction mixture was quenched with 40mL of water. The organic layer was dried with anhydrousNa2SO4 and concentrated under reduced pressure. The residue was purified with chromatography column to give 1.7g white solid, 73.5%.

Reference： [1]Patent: EP3388433,2018,A1 .Location in patent: Paragraph 0168; 0170

55
2-(3-fluorophenyl)-3-oxo-6-[6-(trifluoromethyl)pyridin-3-yl]-2,3-dihydropyridazine-4-carboxylic acid [ No CAS ]
[ 68327-04-8 ]
2-(3-fluorophenyl)-N-[(1S,2S)-2-hydroxycyclopentyl]-3-oxo-6-[6-(trifluoromethyl)pyridin-3-yl]-2,3-dihydropyridazine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	General procedure: Carboxylic acid (1 eq.) was dissolved in anhydrous dimethylformamide. Amine (1-2 eq.), N- ethyl-N-diisopropylamine (4 eq.) and propane phosphonic acid anhydride (T3P, 1.5 eq., 50% in DMF) were successively added. After stirring over night at rt the reaction mixture was purified directly by HPLC or quenched with water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous ammonium hydrochloride solution, dried over sodium sulfate, filtered and concentrated under vacuum to yield the crude title compound. In general the crude products were purified by RP-HPLC (methods A-D depending on polarity). It is also possible to apply the reaction mixture immediately to RP- HPLC.

Reference： [1]Patent: WO2019/101643,2019,A1 .Location in patent: Page/Page column 75; 78

56
[ 589-15-1 ]
[ 68327-04-8 ]
C₁₂H₁₆BrNO [ No CAS ]

Reference： [1]Patent: WO2017/39331,2017,A1 .Location in patent: Paragraph 1842-1848

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H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 68327-04-8 ]

Quality Control of [ 68327-04-8 ]

Related Doc. of [ 68327-04-8 ]

Product Details of [ 68327-04-8 ]

Calculated chemistry of [ 68327-04-8 ]

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Druglikeness

Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 68327-04-8 ]

[ 68327-04-8 ] Synthesis Path-Upstream 1~3

[ 68327-04-8 ] Synthesis Path-Downstream 1~56

Related Functional Groups of [ 68327-04-8 ]

Aliphatic Cyclic Hydrocarbons

Alcohols

Amines

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[ 68327-04-8 ]