[ CAS No. 6850-39-1 ] {[proInfo.proName]}

Name: 6850-39-1|3-Aminocyclohexanol|97%
Brand: Ambeed
SKU: A120648
Price: 5.0 USD
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Quality Control of [ 6850-39-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 6850-39-1 ]

Product Details of [ 6850-39-1 ]

CAS No. :	6850-39-1	MDL No. :	MFCD03790923
Formula :	C₆H₁₃NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NIQIPYGXPZUDDP-UHFFFAOYSA-N
M.W :	115.17	Pubchem ID :	11240459
Synonyms :

Calculated chemistry of [ 6850-39-1 ]

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 :	32.71
TPSA :	46.25 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) :	-7.05 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.38
Log Po/w (XLOGP3) :	-0.06
Log Po/w (WLOGP) :	0.25
Log Po/w (MLOGP) :	0.21
Log Po/w (SILICOS-IT) :	0.39
Consensus Log Po/w :	0.43

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.52
Solubility :	35.1 mg/ml ; 0.305 mol/l
Class :	Very soluble
Log S (Ali) :	-0.46
Solubility :	39.9 mg/ml ; 0.347 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.1
Solubility :	92.3 mg/ml ; 0.802 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.99

Safety of [ 6850-39-1 ]

Signal Word:	Danger	Class:	9
Precautionary Statements:	P264-P270-P271-P272-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P501	UN#:	3077
Hazard Statements:	H302-H314-H317-H410	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 6850-39-1 ]

* 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 [ 6850-39-1 ]
Downstream synthetic route of [ 6850-39-1 ]

[ 6850-39-1 ] Synthesis Path-Upstream 1~3

1
[ 6850-39-1 ]
[ 885280-38-6 ]

Reference： [1] Patent: US2015/175557, 2015, A1,

2
[ 6850-39-1 ]
[ 501-53-1 ]
[ 955406-36-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium carbonate In water; ethyl acetate at 20℃; for 12 h;	Treat a mixture of 3-hydroxycyclohexyl amine (10 g, 86.96 mmol), potassium carbonate (18 g, 130 mmol), ethyl acetate (150 mL) and water (70 mL) with benzyl chloroformate (22.17 g, 130 mmol). Stir the reaction at room temperature for 12 hours. Separate the organic layer, dry the organic over sodium sulfate, filter and concentrate. Add diethyl ether to the residuer. Filter the resulting white precipitate and air dry to afford 19.1 g of the title compound (88percent). MS (m/z): 250 (M+).

Reference： [1] Patent: US2009/111800, 2009, A1, . Location in patent: Page/Page column 40
[2] Patent: WO2014/145512, 2014, A2, . Location in patent: Page/Page column 136; 137

3
[ 24424-99-5 ]
[ 6850-39-1 ]
[ 610302-03-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	at 50℃; for 16 h;	C. tert-butyl(3-Hydroxycyclohexyl)carbamate To a solution of 3-aminocyclohexanol (3.0 g, 26.0 mol) in THF (30 mL) was added di-tert-butyl dicarbonate (6.74 g, 31.2 mmol). The resulting mixture was stirred at 50° C. for 16 h. Then the reaction mixture was concentrated in vacuum and purified by silica gel column chromatography (30percent ethyl acetate in petroleum ether) to afford the desired compound (4.40 g, 20.46 mmol, 78percent yield). MS (ESI) m/z 216.1 [M+H]⁺.

Reference： [1] Patent: US2015/175557, 2015, A1, . Location in patent: Paragraph 0382
[2] Patent: WO2015/25197, 2015, A1, . Location in patent: Paragraph 000140

[ 6850-39-1 ] Synthesis Path-Downstream 1~88

1
[ 6850-39-1 ]
[ 764-59-0 ]

Reference： [1]Journal of the Chemical Society,1957,p. 2937,2940

2
[ 621-42-1 ]
[ 6850-39-1 ]

Reference： [1]Helvetica Chimica Acta,1967,vol. 50,p. 231 - 244

3
[ 6850-39-1 ]
[ 721884-82-8 ]

Reference： [1]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455
[2]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455

4
[ 6850-39-1 ]
[ 13941-94-1 ]

Reference： [1]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455

5
[ 6850-39-1 ]
[ 721884-81-7 ]

Reference： [1]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455
[2]Organic process research and development,2011,vol. 15,p. 294 - 300
[3]Organic process research and development,2011,vol. 15,p. 294 - 300

6
[ 6850-39-1 ]
[ 721884-88-4 ]

Reference： [1]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455

7
[ 6850-39-1 ]
(R,R)-1-acetoxy-3-benzylamidocyclohexane [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455

8
[ 6850-39-1 ]
(S,S)-1-acetoxy-3-benzylamidocyclohexane [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455

9
[ 6850-39-1 ]
(rac)-trans-1-acetoxy-3-benzylamidocyclohexane [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,2004,vol. 15,p. 1451 - 1455

10
[ 764-59-0 ]
[ 6850-39-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1996,p. 895 - 905

11
[ 177366-86-8 ]
[ 6850-39-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1996,p. 895 - 905

12
[ 6850-39-1 ]
[ 30720-25-3 ]
ethyl 1-ethyl-4-[(1SR,3RS)-3-hydroxycyclohexyl]amino}-1H-pyrazolo[3,4-b]pyridine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In ethanol; acetonitrile; at 20 - 85℃; for 17.0h;	3-Aminocyclohexanol (0.677g, 5.9mmol, as described in [J CHEM. SOC., PERKIN TRANS] [1,] 1994, 537) in acetonitrile [(LOML)] and ethanol [(LML)] was added at room temperature to a stirred solution of Intermediate 1 (1.24g, 4. [9MMOL)] and diisopropylethylamine (4. [26ML,] 24. [5MMOL)] in acetonitrile (25ml). The resulting mixture was stirred at [85C] for 17h. The mixture was concentrated in vacuo, and the residue was partitioned between DCM [(50ML)] and water [(10ML).] The phases were separated and the organic phase was dried [(NA2S04)] and evaporated to give an orange-brown oil. The oil was purified by Biotage chromatography (silica [100G)] eluting with 30-50% EtOAc in cyclohexane to give Example 665 as a white foam (0. 681g). LCMS showed MH+= 333; TRET= 2. [76MIN.]

Reference： [1]Patent: WO2004/24728,2004,A2 .Location in patent: Page 241

13
C₂₀H₁₄Cl₃F₃N₂O₄S [ No CAS ]
[ 6850-39-1 ]
4-[1-(2,4-dichlorophenyl)-3-([(1R,3R)-3-hydroxycyclohexyl]amino}carbonyl)-4-methyl-1H-pyrazol-5-yl]phenyl 3,3,3-trifluoropropane-1-sulfonate [ No CAS ]
4-[1-(2,4-dichlorophenyl)-3-([(1R,3S)-3-hydroxycyclohexyl]amino}carbonyl)-4-methyl-1H-pyrazol-5-yl]phenyl 3,3,3-trifluoropropane-1-sulfonate [ No CAS ]
4-[1-(2,4-dichlorophenyl)-3-([(1S,3R)-3-hydroxycyclohexyl]amino}carbonyl)-4-methyl-1H-pyrazol-5-yl]phenyl 3,3,3-trifluoropropane-1-sulfonate [ No CAS ]
4-[1-(2,4-dichlorophenyl)-3-([(1S,3S)-3-hydroxycyclohexyl]amino}carbonyl)-4-methyl-1H-pyrazol-5-yl]phenyl 3,3,3-trifluoropropane-1-sulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; water; at 20℃; for 24.0h;	Step E: 4-(l-(2,4-dichlorophenyl)-3-[(3-hydroxycyclohexyl)amino]carbonyl}-4-methyl- lH-pyrazol-5-yl)phenyl 3 ,3 ,3-trifluoropropane- 1 -sulfonateOxalyl chloride (ImI) was added to l-(2,4-dichlorophenyl)-4-methyl-5-(4-[(3,3,3- trifluoropropyl)sulfonyl]oxy}phenyl)-lH-pyrazole-3-carboxylic acid (314 mg, crude) in DCM (10 ml). One drop of DMF was added and the reaction continued at room temperature for 35 minutes. The solvent and excess oxalyl chloride was evaporated at reduced pressure. The acid chloride was suspended in DCM (5 ml) and added to 3- EPO <DP n="63"/>aminocyclohexanol (80 mg, 0.69 mmol) in DCM/K2CO3 (10%, aq) (1:1, 10 ml). The reaction was continued at room temperature for 24 hours. The phases were separated and the organic phase was washed with water and dried over MgSO4 (389 mg, crude). Step F :4-[l-(2,4-dichlorophenyl)-3-([(llUSD',3i?)-3-hvdroxycvclohexyl]amino)carbonyl)-4- methyl- lH-pyrazol-5-yl]phenyl 3,3,3-trifluoropropane-l-sulfonate and 4-[l-(2,4- dichlorophenyl)-3-({f(li?,3^-3-hydroxycyclohexyllamino}carbonyl)-4-methyl-lH- pyrazol-5-yllphenyl 3 ,3 ,3-trifluoropropane-l -sulfonateThe product was separated from its isomer from Step E by prep LC (kromasil C 8 column, ammonium acetate (aq, 0.1 M):acetonitrile, product came at 94% acetonitrile) to give a white powder after freeze drying (141 mg, 26% yield for 6 steps).1H NMR (399.964 MHz) delta 7.42-7.38 (m, IH), 7.30-7.15 (m, 6H), 7.04 (d, IH), 4.10-3.97 (m, IH), 3.80-3.71 (m, IH), 3.50-3.42 (m, 2H), 2.84-2.70 (m, 2H), 2.35 (s, 3H), 2.29-2.21 (m, IH), 2.00-1.14 (m, 8H). HRMS Calcd for [C26H26Cl2F3N3O5 S+H]+: 620.100. Found: 620.104. Example 284-ri-(2,4-dichlorophenyl)-3-([dlS',3tS)-3-hvdroxycyclohexyl]amino\|carbonyl)-4-methyl- lH-pyrazol-5-yl]phenyl 3,3,3-trifluoropropane-l-sulfonate and 4-[l-(2,4-dichlorophenyl)- 3-([(li?,3i?)-3-hvdroxycyclohexyl]amino)carbonyl)-4-methyl-lH-pyrazol-5-yl1phenyl 3,3,3 -trifluoropropane- 1 -sulfonate The product was separated from its isomer, Ex. 27; Step E by prep LC (kromasil C8 column, ammonium acetate (aq, 0.1 M): acetonitrile, product came at 95% acetonitrile) to give a white powder after freeze drying (127 mg, 23% yield for 6 steps). 1HNMR (399.964 MHz) delta 7.42-7.38 (m, IH), 7.30-7.15 (m, 6H), 6.83 (d, IH), 4.44-4.32 (m, IH), 4.14-4.06 (m, IH), 3.50-3.42 (m, 2H), 2.84-2.70 (m, 2H), 2.35 (s, 3H), 2.05-1.35 (m, 9H). HRMS Calcd for [C26H26Cl2F3N3O5S^-H]+: 620.100. Found: 620.101.

Reference： [1]Patent: WO2007/10217,2007,A1 .Location in patent: Page/Page column 61-62

14
1-(4-benzyloxyphenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid chloride [ No CAS ]
[ 6850-39-1 ]
1-[4-(benzyloxy)phenyl]-2-(2,4-dichlorophenyl)-N-(3-hydroxycyclohexyl)-5-methyl-1H-imidazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In dichloromethane; water; at 20℃; for 2.0h;	Step 1 l-r4-(benzyloxy>)phenyll-2-r2.4-dichloroplienyl)-N-f3-hvdroxycyclohexylV5- methyl-lH-imidazole-4-carboxamide l-[4-(benzyloxy)phenyl]-2-(2,4-dichlorophenyl)-5-methyl-lH-imidazole-4-carboxylic acid, prepared as in Ex. 1, Step 3 (2000 mg, 4.41 mmol) was suspended in DCM (50 ml) and oxalyl chloride (2800 mg, 22.06 mmol) was added at rt followed by one drop of DMF. The mixture was stirred at rt for 15 min whereafter the solvents were evaporated under reduced pressure. The acid chloride suspended in DCM (10 ml) was added dropwise to a mixture of <strong>[6850-39-1]3-aminocyclohexanol</strong> (610 mg, 5.29 mmol), IM NaOH (aq) (30 ml) and DCM (30 ml). Strirred at rt for 2 h, adding more of <strong>[6850-39-1]3-aminocyclohexanol</strong> after Ih 25 min (67 mg, 0.58 mmol) and Ih 45 min (58 mg, 0.50 mmol). Water/DCM were added and the phases were separated. The organic phase was washed with HCl (10 %, aq) and brine, dried (MgSO4), filtered and evaporated yield the product (crude 2790 mg).1R NMR (400 MHz, CDCl3) delta 7.40-7.16 (8H, m), 7.03-6.88 (4H, m), 5.01 (2H, s), 4.44- 4.32 (0.5H, m), 4.18-4.11 (0.5H, m), 4.06-3.94 (0.5H, m), 3.76-3.66 (0.5H, m), 2.46 (3H, s), 2.03-1.10 (8H, m). MS m/z 550 (M+H)+.

Reference： [1]Patent: WO2007/31721,2007,A1 .Location in patent: Page/Page column 58

15
[ 98491-29-3 ]
[ 6850-39-1 ]
trans-3-[[(4-methoxymethoxy)phenyl]amino]cyclohexanol [ No CAS ]
cis-3-[[(4-methoxymethoxy)phenyl]amino]cyclohexanol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 2330 - 2344

16
[ 6850-39-1 ]
[ 103-71-9 ]
[ 101265-14-9 ]

Yield	Reaction Conditions	Operation in experiment
69%	In N,N-dimethyl-formamide; at 20℃; for 1.5h;	Example 3; 1- [3-(3-Morpholin-4-yl-propoxy)cy clohexyl] -3-phenylurea (63); Phenyl isocyanate (0.117 mL, 1.08 mmol) was added to a mixture of 3- aminocyclohexanol (B-I) (131 mg, 1.13 mmol) in DMF (2.5 mL). The mixture was stirred at ambient temperature and monitored by LCMS. After 1.5 h, the reaction was complete as determined by LCMS analysis. The mixture was chilled in an ice bath, quenched with H2O (ca. 5 mL ) and 1 N HCl (ca. 3 mL), and extracted into EtOAc (2 x ca. 10 mL). The EtOAc layers were washed with H2O (2 x 10 mL) and brine (5 mL), dried over Na2SO4, and concentrated to provide l-(3-hydroxycyclohexyl)-3-phenylurea (B-2) as a white solid (174 mg, 69%). LCMS m/z 235.2 [M + H]+.

Reference： [1]Patent: WO2008/116145,2008,A2 .Location in patent: Page/Page column 72

17
[ 4411-25-0 ]
[ 6850-39-1 ]
[ 1061378-17-3 ]

Yield	Reaction Conditions	Operation in experiment
74%	In N,N-dimethyl-formamide; at 20℃; for 1.5h;	Example 4; l-adamantan-l-yl-3-[3-(3-morpholin-4-yl-propoxy)cyclohexyl]urea (48); 1-Isocyanato-adamantane (180 mg, 1.02 mmol) was added to a mixture of 3- aminocyclohexanol (B-3) (123 mg, 1.07 mmol) in DMF (2.5 mL). The mixture was stirred at ambient temperature and monitored by LCMS. After 1.5 h, the reaction was determined to be complete by LCMS analysis. The mixture was chilled in an ice bath and quenched with H2O (ca. 5 mL ) and 1 N HCl (ca. 3 mL). After 30 minutes, the white solid that formed was collected by filtration, washed with H2O (ca. 20 mL), and transferred to a round-bottom flask with the aid of MeCN. The MeCN was evaporated and the solid was dried under high vacuum to provide 1 -(3 -Hydroxy eye lohexyl)-3-phenylurea (B-4) as a white solid (220 mg, 74%): LCMS m/z 293.4 [M + H]+.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 4259 - 4263
[2]Patent: WO2008/116145,2008,A2 .Location in patent: Page/Page column 73

18
[ 1124382-78-0 ]
[ 6850-39-1 ]
[ 1124381-49-2 ]

Yield	Reaction Conditions	Operation in experiment
49%	With pyrographite; N-ethyl-N,N-diisopropylamine; In tert-butyl alcohol; at 200℃; for 1.0h;Microwave irradiation;	Example 79 : N-IS-rO-hydroxycyclohexyDaminoin^^ltriazolon^-alpyridin-l- yl} nicotinamide <n="105"/>(79); <strong>[6850-39-1]3-amino-cyclohexanol</strong> (Betapharma, 67.33 mg; 0.58 mmol; 2.0 eq.) was added to a mixture of N-(5-chloro[l,2,4]triazolo[l,5-a]pyridin-2-yl)nicotinamide ((B4), 80 mg; 0.29 mmol; 1.0 eq.), DIEA (76 mg; 0.58 mmol; 2.0 eq.) and activated Charcoal (8 mg) in tBuOH (0.8 mL). The reaction mixture was heated at 2000C for 2 x 30 min under microwave irradiation. After this time, it was filtered on a celite pad and the cake was washed with ACN. The filtrate was directly purified by RP-HPLC (Starting with 15% ACN in water for 5 min, then up to 30% in 10 min.). The title compound was isolated after lyophilisation as a white powder (51 mg, 49%). HPLC, Rt: 2.14 min. (purity 98.0%). LC/MS, M+(ESI): 353.0, M (ESI): 351.0.

Reference： [1]Patent: WO2009/27283,2009,A1 .Location in patent: Page/Page column 103-104

19
[ 6850-39-1 ]
[ 501-53-1 ]
[ 955406-36-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium carbonate; In water; ethyl acetate; at 20.0℃; for 12.0h;	Treat a mixture of 3-hydroxycyclohexyl amine (10 g, 86.96 mmol), potassium carbonate (18 g, 130 mmol), ethyl acetate (150 mL) and water (70 mL) with benzyl chloroformate (22.17 g, 130 mmol). Stir the reaction at room temperature for 12 hours. Separate the organic layer, dry the organic over sodium sulfate, filter and concentrate. Add diethyl ether to the residuer. Filter the resulting white precipitate and air dry to afford 19.1 g of the title compound (88%). MS (m/z): 250 (M+).
	With sodium carbonate; In 1,4-dioxane; water; at 20.0℃;	To a solution of <strong>[6850-39-1]3-aminocyclohexanol</strong> (2.3 g, 20.0 mmol) in H20/1,4-dioxane (20 mL/20 mL) were added Na2CO3 (2.52 g, 30.0 mmol) and benzyl carbonochloridate (5.1 g, 30.0 mmol). The mixture was stirred at room temperature overnight. All of the volatiles were removed under reduced pressure and water (40 mL) was added. The suspension was extracted with EtOAc (2 x 100 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and evaporated to give the crude compound SP-0011379-019 as colorless oil (5.0 g of the crude). LC-MS 249 (M+Na), purity 96% (UV 214 nm).

Reference： [1]Patent: US2009/111800,2009,A1 .Location in patent: Page/Page column 40
[2]Patent: WO2014/145512,2014,A2 .Location in patent: Page/Page column 136; 137

20
[ 6850-39-1 ]
[ 350511-08-9 ]
[ 1093252-79-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5763 - 5765

21
[ 6850-39-1 ]
[ 4942-47-6 ]
[ 1061378-19-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 4259 - 4263

22
[ 1263420-00-3 ]
[ 6850-39-1 ]
[ 1263419-71-1 ]

Yield	Reaction Conditions	Operation in experiment
46%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	To a solution of 4-chloropyrrolo[l,2-b]pyridazine-3-carbonitrile (15g) (0.15 g, 0.84 mmol) in DMF (2.5 mL) was added at room temperature <strong>[6850-39-1]3-aminocyclohexanol</strong> (5In) (194 mgs, 1.68 mmol), DIPEA (0.87 mL, 5 mmol) and stirred at room temperature overnight. The reaction was quenched with water (10 mL) and extracted with ethyl acetate (10 mL). The aqueous layer was separated and extracted with ethyl acetate (2 x 10 mL). The organic layers were combined washed with water (2 x 10 ml), brine (10 mL), dried, filtered and concentrated in vacuum. The residue obtained was purified by flash column chromatography (silica gel 12g, eluting with 0- 100% ethyl acetate in hexanes) to furnish 4-(3-hydroxycyclohexylamino)pyrrolo[l,2- b]pyridazine-3-carbonitrile (51o) (0.105 g, 46 %) as a white solid: 1H NMR (300 MHz, DMSO) delta 7.90 (s, IH), 7.78 (d, J= 8.5 Hz, IH), 7.69 (dd, J= 2.6, 1.6 Hz, IH), 7.12 (dd, J= 4.4, 1.6 Hz, IH), 6.68 (dd, J= 4.4, 2.7 Hz, IH), 4.88 (d, J= 4.3 Hz, IH), 4.25 (m, IH), 3.54 (m, IH), 2.17 (m, IH), 1.92 (m,lH), 1.76 (d, J= 13.3 Hz, 2H), 1.54 - 1.24 (m, 3H), 1.16 (dd, J= 14.6, 10.6 Hz, IH). MS (ES+) 536.3 (2M+Na), MS (ES-) 291.0 (M+Cl).

Reference： [1]Patent: WO2011/14817,2011,A1 .Location in patent: Page/Page column 134

23
[ 943230-31-7 ]
[ 6850-39-1 ]
[ 1073135-74-6 ]

Yield	Reaction Conditions	Operation in experiment
85.1%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃; for 2.0h;	Initially charge 1.0 g (2.97 mmol) of 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine and 513 mg (approx. 4.5 mmol) of (+/-)-cis/trans-<strong>[6850-39-1]3-aminocyclohexanol</strong> (approx. 3:1 cis/trans mixture; prepared according to J. Chem: Soc. Perkin Trans. I, 1994, 537) in 2.7 ml of DMF. After adding 1.03 ml (5.94 mmol) of DIEA, heat the mixture to 120 C. for 2 h. After cooling, add to ice-water. Filter off the precipitated solid with suction, wash with water and dry under reduced pressure. Purify the crude product by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 2:1?1:2). 1.05 g (85.1% of theory) of the target product are obtained as a cis/trans mixture. LC-MS (Method 6): Rt=2.53 min; m/z=416 (M+H)+.

Reference： [1]Patent: US2011/124665,2011,A1 .Location in patent: Page/Page column 30

24
[ 943230-33-9 ]
[ 6850-39-1 ]
(+/-)-cis-3-[(6-phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20.7%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃;	Heat a mixture of 4.0 g (17.34 mmol) of 4-chloro-6-phenylfuro[2,3-d]pyrimidine, 4.5 ml (26 mmol) of DIEA and 2.8 g of (+/-)-cis/trans-<strong>[6850-39-1]3-aminocyclohexanol</strong> (approx. 85% strength, approx. 20.8 mmol; approx. 3:1 cis/trans mixture; prepared according to J. Chem. Soc. Perkin Trans. I, 1994, 537) in 15 ml of DMF is heated to 120 C. overnight. After cooling, add the reaction mixture to water and extract three times with ethyl acetate. Wash the combined organic phases with saturated sodium chloride solution, dry over magnesium sulphate and concentrate under reduced pressure. Repeated stirring of the crude product with a mixture of methyl tert-butyl ether and dichloromethane enriches the product in the mother liquor. After concentrating the mother liquor, filter off the product with suction after crystallization from dichloromethane/methanol (10:1) and dry it under reduced pressure. 1.11 g (20.7% of theory) of the target product are obtained. LC-MS (Method 6): Rt=1.95 min; m/z=310 (M+H)+ 1-NMR (400 MHz, DMSO-d6): delta=8.25 (s, 1H), 7.88-7.72 (m, 3H), 7.55-7.47 (m, 2H), 7.46-7.38 (m, 2H), 4.71 (d, 1H), 4.11-4.01 (m, 1H), 3.59-3.47 (m, 1H), 2.19 (d, 1H), 1.96-1.19 (m, 3H), 1.36-1.05 (m, 4H).

Reference： [1]Patent: US2011/124665,2011,A1 .Location in patent: Page/Page column 30

25
[ 17199-29-0 ]
[ 6850-39-1 ]
[ 1257303-73-3 ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

26
[ 611-71-2 ]
[ 6850-39-1 ]
[ 1257303-70-0 ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

27
[ 6850-39-1 ]
((1R,3S)-3-hydroxycyclohexyl)carbamic acid benzyl ester [ No CAS ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

28
[ 6850-39-1 ]
((1S,3R)-3-hydroxycyclohexyl)carbamic acid benzyl ester [ No CAS ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

29
[ 6850-39-1 ]
((1S,3S)-3-hydroxycyclohexyl)carbamic acid benzyl ester [ No CAS ]
[ 750649-42-4 ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

30
[ 6850-39-1 ]
acetic acid (1R,3S)-3-(benzyloxycarbonylamino)cyclohexyl ester [ No CAS ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

31
[ 6850-39-1 ]
[ 501-53-1 ]
(+/-)-trans-(3-hydroxycyclohexyl)carbamic acid benzyl ester [ No CAS ]
(+/-)-cis-(3-hydroxycyclohexyl)carbamic acid benzyl ester [ No CAS ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

32
[ 6850-39-1 ]
[ 611-71-2 ]
trans-(3-hydroxycyclohexyl)ammonium (R/S)-mandelate [ No CAS ]
cis-(3-hydroxycyclohexyl)ammonium (R/S)-mandelate [ No CAS ]

Reference： [1]Organic process research and development,2011,vol. 15,p. 294 - 300

33
[ 6850-39-1 ]
[ 123-11-5 ]
[ 1214923-66-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; at 20℃; for 0.5h;	To a vigorously stirred solution of <strong>[6850-39-1]3-aminocyclohexanol</strong> (0.9 g, 7.81 mmol) in aqueous sodium hydroxide (1 mL, 1 M) at rt was added 4-methoxybenzaldehyde (1.12 g, 8.20 mmol). The reaction mixture was stirred for 30 min The solids were collected by vacuum filtration, washed with water, and then dried to afford crude 3-[1-(4-Methoxy-phenyl)-meth-(E)-ylidene]-amino}-cyclohexanol which was used without further manipulation.

Reference： [1]Patent: US2011/294801,2011,A1 .Location in patent: Page/Page column 12; 29

34
[ 6850-39-1 ]
[ 123-11-5 ]
[ 1214923-67-7 ]

Reference： [1]Patent: US2011/294801,2011,A1

35
[ 6850-39-1 ]
[ 1214923-68-8 ]

Reference： [1]Patent: US2011/294801,2011,A1

36
[ 6850-39-1 ]
[ 1214923-69-9 ]

Reference： [1]Patent: US2011/294801,2011,A1

37
[ 6850-39-1 ]
[ 1214923-70-2 ]

Reference： [1]Patent: US2011/294801,2011,A1

38
[ 6850-39-1 ]
[ 1214923-02-0 ]

Reference： [1]Patent: US2011/294801,2011,A1

39
[ 6850-39-1 ]
[ 1259278-61-9 ]

Reference： [1]Patent: US2012/171245,2012,A1
[2]Patent: JP2015/38146,2015,A

40
[ 6850-39-1 ]
[ 1259364-51-6 ]

Reference： [1]Patent: US2012/171245,2012,A1
[2]Patent: JP2015/38146,2015,A

41
[ 1259009-31-8 ]
[ 6850-39-1 ]
[ 1259278-66-4 ]

Yield	Reaction Conditions	Operation in experiment
	With DIEA; In tetrahydrofuran;	Formation of (S)-3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)cyclohexanol (27a) To a solution of 5-chloro-3-(5-fluoro-4-(methylsulfonyl)pyrimidin-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine, 1a, (1.09 g, 2.34 mmol) and <strong>[6850-39-1]3-aminocyclohexanol</strong> (0.32 g, 2.82 mmol) in THF was added DIEA (0.60 g, 4.69 mmol). The reaction mixture was heated at 130 C. in microwave for 10 min. The solvent was removed under reduced pressure and the resulting residue was purified by silica gel chromatography to afford 550 mg of the desired product, 27a.

Reference： [1]Patent: US2012/171245,2012,A1

42
[ 6850-39-1 ]
C₂₂H₂₅N₅O₅S₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7627 - 7633

43
[ 6850-39-1 ]
C₂₁H₂₃N₅O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7627 - 7633

44
[ 6850-39-1 ]
C₂₆H₃₁N₅O₅S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7627 - 7633

45
[ 6850-39-1 ]
C₁₉H₂₂N₄O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7627 - 7633

46
[ 6850-39-1 ]
C₁₆H₂₁N₅O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7627 - 7633

47
[ 1245649-52-8 ]
[ 6850-39-1 ]
C₁₉H₂₀N₄O₅S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7627 - 7633

48
[ 1572515-74-2 ]
[ 6850-39-1 ]
[ 1572511-71-7 ]
[ 1572511-68-2 ]
[ 1572511-77-3 ]
[ 1572511-74-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 1.0h;	Compound 134 was separated in it's isomers by preparative SFC (Stationary phase: Chiralpak Daicel IC 20 x 250 mm), Mobile phase: C02, iPrOH with 0.4% iPrNH2), the desired fractions were collected, evaporated, dissolved in MeOH and evaporated again, yielding 134a, 134b, 134c, 134d. SFC Columns: ID-H 250 mm x 4.6 mm Flow: 3 ml/min Mobile phase: 25 % iPrOH (containing 0.2% iPrNH2) hold 18.0 min. Temperature: 30C; Rt: 134 a (10.0 min), 134b (11.1 min), 134c (13.6 min), 134d (14.7 min). Cis: Enantiomers 134a and 134b N-(4-fluoro-3-methyl-phenyl)-3- [[(lR,3S)-3-hydroxycyclohexyl]sulfamoyl]benzamide or N-(4-fluoro-3-methyl- phenyl)-3-[[(lS,3R)-3-hydroxycyclohexyl]sulfamoyl]benzamide. 1H NMR (400 MHz, DMSO-de ) delta ppm 0.84 - 1.14 (m, 4 H), 1.48 - 1.60 (m, 2 H), 1.60-1.72 (m, 1 H), 1.72 - 1.82 (m, 1 H), 2.26 (d, J=1.8 Hz, 3 H), 2.93 - 3.07 (m, 1 H), 3.20 - 3.30 (m, 1 H), 4.58 (d, J=4.6 Hz, 1 H), 7.14 (t, J=9.1 Hz, 1 H), 7.55 - 7.64 (m, 1 H), 7.69 (dd, J=7.0, 2.2 Hz, 1 H), 7.76 (t, J=7.8 Hz, 1 H), 7.83 (br. s., 1 H), 7.96 - 8.06 (m, 1 H), 8.13 - 8.24 (m, 1 H), 8.38 (t, J=1.7 Hz, 1 H), 10.47 (s, 1 H) Trans: enantiomers 134c and 134d N-(4-fluoro-3-methyl-phenyl)-3-[[(lR,3R)-3 hydroxycyclohexyl]sulfamoyl]benzamide or N-(4-fluoro-3-methyl-phenyl)-3- [[(1 S,3S)-3-hydroxycyclohexyl]sulfamoyl]benzamide 1H NMR (400 MHz, DMSO-d6 ) delta ppm 1.08 - 1.20 (m, 1 H), 1.25 - 1.42 (m, 4 H), 1.42 - 1.58 (m, 3 H), 2.25 (d, J=1.8 Hz, 3 H), 3.36 - 3.45 (m, 1 H), 3.71 - 3.89 (m, 1 H), 4.38 (d, J=3.5 Hz, 1 H), 7.14 (t, J=9.1 Hz, 1 H), 7.51 (br. s., 1 H), 7.56 - 7.63 (m, 1 H), 7.69 (dd, J=7.2, 2.3 Hz, 1 H), 7.73 - 7.78 (m, 1 H), 7.97 - 8.05 (m, 1 H), 8.19 (dt, J=7.9, 1.2 Hz, 1 H), 8.37 (t, J=1.7 Hz, 1 H), 10.47 (br. s., 1 H) Procedure S3: To a solution of 3-[(4-fluoro-3-methyl-phenyl)carbamoyl]benzene- sulfonyl chloride (0.50 g, 1.52 mmol, 1 eq) and DIPEA (657 mu, 3.81 mmol, 2.5 eq) in CH2CI2 (10 mL), an amine (1.1 eq) was added. The reaction mixture was stirred for 1 hour. Next, 1M HC1 (5 mL) was added to the reaction mixture. Workup W2: The organic layer was separated and concentrated in vacuo. The obtained residue was purified by silica gel column chromatography using a heptane to EtOAc gradient as eluent.

Reference： [1]Patent: WO2014/33170,2014,A1 .Location in patent: Page/Page column 78; 79; 81

49
[ 6850-39-1 ]
benzyl (3-oxocyclohexyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2
[2]Patent: US2009/111800,2009,A1

50
[ 6850-39-1 ]
[ 884306-55-2 ]

Reference： [1]Patent: WO2014/145512,2014,A2

51
[ 6850-39-1 ]
[ 884306-54-1 ]

Reference： [1]Patent: WO2014/145512,2014,A2

52
[ 6850-39-1 ]
[ 1073633-17-6 ]

Reference： [1]Patent: WO2014/145512,2014,A2

53
[ 6850-39-1 ]
C₁₇H₁₆FN₅ [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

54
[ 6850-39-1 ]
C₁₉H₁₈FN₅O [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

55
[ 6850-39-1 ]
C₉H₁₃N₃ [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

56
[ 6850-39-1 ]
C₁₇H₁₆FN₅ [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

57
[ 6850-39-1 ]
C₁₉H₁₈FN₅O [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

58
[ 6850-39-1 ]
C₂₂H₂₄FN₅O₂ [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

59
[ 6850-39-1 ]
C₁₈H₁₈FN₅O₂S [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

60
[ 6850-39-1 ]
C₁₇H₁₆ClN₅ [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

61
[ 6850-39-1 ]
C₁₉H₁₈ClN₅O [ No CAS ]

Reference： [1]Patent: WO2014/145512,2014,A2

62
[ 6850-39-1 ]
[ 18162-48-6 ]
[ 1642816-19-0 ]