[ CAS No. 71690-05-6 ] {[proInfo.proName]}

Name: 71690-05-6|5,6-Dichloronicotinaldehyde|95%
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Quality Control of [ 71690-05-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 71690-05-6 ]

CAS No. :	71690-05-6	MDL No. :	MFCD08448226
Formula :	C₆H₃Cl₂NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ROSCFXKNBQZLFC-UHFFFAOYSA-N
M.W :	176.00	Pubchem ID :	11535654
Synonyms :

Calculated chemistry of [ 71690-05-6 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	39.64
TPSA :	29.96 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.0 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.36
Log Po/w (XLOGP3) :	1.94
Log Po/w (WLOGP) :	2.2
Log Po/w (MLOGP) :	1.0
Log Po/w (SILICOS-IT) :	2.79
Consensus Log Po/w :	1.86

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.53
Solubility :	0.518 mg/ml ; 0.00294 mol/l
Class :	Soluble
Log S (Ali) :	-2.19
Solubility :	1.13 mg/ml ; 0.0064 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.2
Solubility :	0.111 mg/ml ; 0.000628 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.53

Safety of [ 71690-05-6 ]

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

Application In Synthesis of [ 71690-05-6 ]

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

Upstream synthesis route of [ 71690-05-6 ]
Downstream synthetic route of [ 71690-05-6 ]

[ 71690-05-6 ] Synthesis Path-Upstream 1~5

1
[ 54127-30-9 ]
[ 71690-05-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With manganese(IV) oxide In dichloromethane at 25℃; for 48 h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxymethylpyridine (3, 8.10 g, 50.0 mmol, Sigma-Aldrich, St. Louis, Mo.) in anhydrous CH₂Cl₂(150 mL). The reaction mixture was stirred at a temperature of about 25° C. for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0percent-40percent)/hexanes to provide 7.2 g of 4 (90percent yield). ¹H NMR (400 MHz, CDCl₃) δ 10.08 (1H, s), 8.77 (1H, d, J=1.97 Hz), 8.25 (1H, d, J=1.97 Hz). LC/MS (M+1): 176.
90%	With manganese(IV) oxide In dichloromethane at 25℃; for 48 h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (3, 8.10 g, 50.0 mmol, Sigma-Aldrich, St. Louis, Mo.) in anhydrous CH₂Cl₂(150 mL). The reaction mixture was stirred at a temperature of about 25° C. for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0percent-40percent)/hexanes to provide 7.2 g of 4 (90percent yield). ¹H NMR (400 MHz, CDCl₃) δ 10.08 (1H, s), 8.77 (1H, d, J=1.97 Hz), 8.25 (1H, d, J=1.97 Hz). LC/MS (M+1): 176.
90%	With manganese(IV) oxide In dichloromethane at 25℃; for 48 h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (3, 8.10 g, 50.0 mmol, Sigma-Aldrich, St. Louis, Mo.) in anhydrous CH₂Cl₂(150 mL). The reaction mixture was stirred at a temperature of about 25° C. for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0percent-40percent)/hexanes to provide 7.2 g of 4 (90percent yield). ¹H NMR (400 MHz, CDCl₃) δ 10.08 (1H, s), 8.77 (1H, d, J=1.97 Hz), 8.25 (1H, d, J=1.97 Hz). LC/MS (M+1): 176.

90%	With manganese(IV) oxide In dichloromethane at 25℃; for 48 h;	2,3-Dichloro-5-formylpyridine. To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (64, 8.10 g, 50.0 mmol) in anhydrous CH₂CIo ( 150 mL). The reaction mixture was stirred at a temperature of about 25⁰C for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0percent-40percent)/hexanes to provide 7.2 g of 65 (90percent yield). ¹H NMR (400 MHz, CDCl₃) δ 10.08 (IH, s), 8.77 (I H, d, J=1.97 Hz), 8.25 (IH, d, J=1.97 Hz). LC/MS (M+1 ): 176.
90%	With manganese(IV) oxide In dichloromethane at 20℃; for 48 h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (1, 8.10 g, 50.0 mMol) in <n="70"/>anhydrous CH₂Cl₂ (150 mL). The resulting mixture was stirred at room temperature for 2 days, which was filtered through Celite and concentrated. The crude mixture was purified by a silica gel chromatography column eluting with a gradient of ethyl acetate (0-40percent)/hexanes to give 7.2 g of the desired product 2 (90percent). ¹H NMR (400 MHz, CDCl₃) δ 10.08 (1 H, s), 8.77 (1 H, d, J = 1.97 Hz), 8.25 (1 H, d, J = 1.97 Hz). LC/MS (M+l): 176.
88%	With Dess-Martin periodane In dichloromethane at 0℃; for 0.5 h; Inert atmosphere	To a solution of (5,6-dichloropyridin-3-yl)methanol (23) (1 g, 5.62 mmol) in CH₂Cl₂(40 ml) was added Dess-Martin (2.6 g, 6.18 mmol) at 0° C. under nitrogen. (0747) After being stirred for 30 min at 0° C., the reaction mixture was quenched with sat. NaHCO₃and diluted with CH₂Cl₂. The resulting organic layer was separated and the aqueous layer was extracted with CH₂Cl₂, the combined organic layers were washed with Na₂S₂O₃, H₂O and brine, dried over Na₂SO₄and concentrated in vacuo. The residue was triturated with CHCl₃. The resulting solid was filtered through a glass funnel, rinsed with CHCl₃. The liquid residue was chromatographed on silica gel eluting with a gradient of hexane/ethyl acetate (10-20percent) to afford 867 mg of the desired product (24) in 88percent yield as a white solid. ¹H-NMR (DMSO-d6) δ: 10.09 (1H, s), 8.90 (1H, s), 8.55 (1H, s). LC/MS (M+1): 176.
22%	Stage #1: With 4-methylmorpholine N-oxide In dichloromethane at 20℃; for 0.166667 h; Molecular sieve Stage #2: With tetrapropylammonium perruthennate In dichloromethane	To a solution of (5,6-dichloro-3-pyridinyl)methanol (200 mg) in CH₂Cl₂, molecular sieves (3A) (55 mg) and 4-methy-morpholine-N-oxide (198 mg) was added and stirred at room temperature for 10 minutes. Then tetra-n-propylammonium perruthenate(VII) (38 mg) was added and stirred overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under vacuum. The residue obtained was purified by chromatography column on silica gel using a mixture of EtOAc/hexane as eluent to give 44 mg (22percent) of the title compound. ¹H-NMR (δ, ppm, CDCl₃): 10.09 (s, 1 H), 8.77 (s, 1 H), 8.25 (s, 1 H).
22%	Stage #1: With 4-methylmorpholine N-oxide In dichloromethane at 20℃; for 0.166667 h; Molecular sieve Stage #2: With tetrapropylammonium perruthennate In dichloromethane	Preparation 2; 5,6-Dichloro-3-pyridinecarbaldehyde (Used to prepare Example 15) To a solution of (5,6-dichloro-3-pyridinyl)methanol (200 mg) in DCM, molecular sieves (3A) (55 mg) and 4-methyl-morpholine-N-oxide (198 mg) was added and stirred at room temperature for 10 minutes. Then tetra-n-propylammonium perruthenate (VII) (38 mg) was added and stirred overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under vacuum. The residue obtained was purified by chromatography column on silica gel using a mixture of EtOAc/hexane as eluent to give 44 mg (22percent) of the title compound.¹H-NMR (δ, ppm, CDCl₃): 10.09 (s, 1H), 8.77 (s, 1H), 8.25 (s, 1H).

Reference： [1] Patent: US2010/120862, 2010, A1, . Location in patent: Page/Page column 94
[2] Patent: US2010/137306, 2010, A1, . Location in patent: Page/Page column 169
[3] Patent: US2010/130499, 2010, A1, . Location in patent: Page/Page column 122
[4] Patent: WO2008/132600, 2008, A2, . Location in patent: Page/Page column 258
[5] Patent: WO2008/133973, 2008, A1, . Location in patent: Page/Page column 68-69
[6] Patent: US9156830, 2015, B2, . Location in patent: Page/Page column 91-92
[7] Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3719 - 3742
[8] Patent: EP2080761, 2009, A1, . Location in patent: Page/Page column 39-40
[9] Patent: US2009/306089, 2009, A1, . Location in patent: Page/Page column 25-26
[10] Patent: WO2004/35549, 2004, A1, . Location in patent: Page 164
[11] Patent: WO2010/92342, 2010, A1, . Location in patent: Page/Page column 48
[12] Patent: WO2011/79305, 2011, A1, . Location in patent: Page/Page column 43
[13] Journal of Medicinal Chemistry, 2011, vol. 54, # 11, p. 3793 - 3816

2
[ 162327-73-3 ]
[ 71690-05-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With lithium aluminium tetrahydride In tetrahydrofuran at -78℃; for 0.5 h;	A 2M solution of LiAIH4 in THF (1 9.2mL, 38.2gmmol) was added to a solution of 5,6-dichloro-N-methoxy-N-methylnicotinamide (22g, 76.59mo1) in THE (360mL) at -78°C and stirred for 30 mm at sametemperature. The RM was quenched with sat. Na2SO4 solution and filtered the salts through celite bed, washed with EtOAc. The filtrate was dried (anhydr. Na2SO4), filtered and evaporated the solvent under vacuo to give crude as a thick liquid. The crude was purified by CC (0-5percent EtOAc in PE) to give 12g (75percent) of 5,6-dichloronicotinaldehyde as liquid.

Reference： [1] Patent: WO2015/158427, 2015, A1, . Location in patent: Page/Page column 90; 91
[2] Patent: WO2008/75757, 2008, A1, . Location in patent: Page/Page column 36

3
[ 41667-95-2 ]
[ 71690-05-6 ]

Reference： [1] Tetrahedron, 2002, vol. 58, # 37, p. 7381 - 7389
[2] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 10, p. 3001 - 3006
[3] Patent: WO2015/158427, 2015, A1,

4
[ 54127-29-6 ]
[ 71690-05-6 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1932, vol. <2>134, p. 177,184
[2] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 10, p. 3001 - 3006

5
[ 71690-05-6 ]
[ 54127-30-9 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1932, vol. <2>134, p. 177,184

[ 71690-05-6 ] Synthesis Path-Downstream 1~88

1
[ 54127-29-6 ]
[ 71690-05-6 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1932,vol. <2>134,p. 177,184
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3001 - 3006

2
[ 71690-05-6 ]
[ 75-16-1 ]
[ 683243-82-5 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at 0℃; for 0.5h;	b) (1S,1R)-1-(5, 6-Dichloro-pyridin-3-yl) -ethanol. MeMgBr (2.5 mL, 7.5 mmol, 3.0 M in ether, Aldrich) was added dropwise to a solution of 5, 6-dichloro-pyridine-3-carbaldehyde from step (a) above (880 mg, 5.0 mmol) in THF (20 mL, Aldrich) with stirring at 0 [C.] The mixture was stirred at [0 C FOR] 30 min, saturated aqueous solution [OF NH4C1] (20 mL) was added, and the mixture was extracted with EtOAc (2 x 40 mL). The combined organic extracts were washed with brine (20 mL), dried over [NA2S04] and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography, eluting with 40% [ETOAC/HEXANE] to give the title compound. MS (ESI, pos. ion) [TNLZ] : 192 [(M+1).]
		2.50 Example 50 (Prepared according to Scheme 10); (2R)-4-(3-Chloro-5-(l-hydroxyethyl)pyridin-2-yl)-2-methyl-N-(4-(trimethylsilyl)phenyl)piperazine-l- carboxamide; A solution of (5,6-dichloropyridin-3-yl) methanol (5.62mmol) and manganese dioxide (52mmol) in DCM (50 ml) was stirred at room temperature for 4 days. The reaction was filtered through celite, washed with EtOH and concentrated under reduced pressure yielding the crude product which was used without purification, 5,6- dichloronictoninaldehyde. To a solution of the crude 5,6-dichloronictoninaldehyde (3.24mmol) in THF (20ml) at -78 0C was added methyl magnesium bromide (9.72mmol) in a dropwise fashion. The reaction was allowed to warm to room temperature overnight. The reaction was quenched with saturated ammonium chloride (50ml) and extracted with ethyl acetate (50 ml) The organic phase was separated, dried with a phase separation cartridge and concentrated under reduced pressure yielding the crude oil which was purified by flash chromatography (0-30% ethyl acetate in petroleum ether) yielding the product. l-(5,6-dichloropyridin- 3-yl)ethanol (2.14mmol).MS: ES+ 191.9. 1H NMR (400 MHz, CDCl3) delta 8.29 (s, IH), 7.75 - 8.03 (m, IH), 4.92 - 5.11 (m, IH), 2.11 - 2.26 (m, IH), 1.45 - 1.56 (m, 3H)The title compound was synthesised in accordance with Example 23 using (R)-(+)-2-methylpiperazine and the above intermediate l-(5,6-dichloropyridin-3-yl)ethanol.MS: ES+ 447.2. 1H NMR (400 MHz, CDCl3) delta 8.07 (s, IH), 7.60 (t, IH), 7.32 - 7.40 (m, 2H), 7.24 - 7.31 (m, 2H), 6.26 (s, IH), 4.74 - 4.85 (m, IH), 4.21 - 4.32 (m, IH), 3.76 - 3.88 (m, IH), 3.59 - 3.74 (m, 2H), 3.30 - 3.43 (m, IH), 2.93 - 3.04 (m, IH), 2.80 - 2.93 (m, IH), 1.71 - 1.77 (m, IH), 1.38 - 1.44 (m, 3H), 1.32 - 1.38 (m, 3H), 0.15 (s, 9H)

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3719 - 3742
[2]Patent: WO2004/35549,2004,A1 .Location in patent: Page 164-165
[3]Patent: WO2010/92342,2010,A1 .Location in patent: Page/Page column 48

3
[ 54127-30-9 ]
[ 71690-05-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With manganese(IV) oxide; In dichloromethane; at 25℃; for 48h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxymethylpyridine (3, 8.10 g, 50.0 mmol, Sigma-Aldrich, St. Louis, Mo.) in anhydrous CH2Cl2 (150 mL). The reaction mixture was stirred at a temperature of about 25 C. for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0%-40%)/hexanes to provide 7.2 g of 4 (90% yield). 1H NMR (400 MHz, CDCl3) delta 10.08 (1H, s), 8.77 (1H, d, J=1.97 Hz), 8.25 (1H, d, J=1.97 Hz). LC/MS (M+1): 176.
90%	With manganese(IV) oxide; In dichloromethane; at 25℃; for 48h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (3, 8.10 g, 50.0 mmol, Sigma-Aldrich, St. Louis, Mo.) in anhydrous CH2Cl2 (150 mL). The reaction mixture was stirred at a temperature of about 25 C. for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0%-40%)/hexanes to provide 7.2 g of 4 (90% yield). 1H NMR (400 MHz, CDCl3) delta 10.08 (1H, s), 8.77 (1H, d, J=1.97 Hz), 8.25 (1H, d, J=1.97 Hz). LC/MS (M+1): 176.
90%	With manganese(IV) oxide; In dichloromethane; at 25℃; for 48h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (3, 8.10 g, 50.0 mmol, Sigma-Aldrich, St. Louis, Mo.) in anhydrous CH2Cl2 (150 mL). The reaction mixture was stirred at a temperature of about 25 C. for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0%-40%)/hexanes to provide 7.2 g of 4 (90% yield). 1H NMR (400 MHz, CDCl3) delta 10.08 (1H, s), 8.77 (1H, d, J=1.97 Hz), 8.25 (1H, d, J=1.97 Hz). LC/MS (M+1): 176.

90%	With manganese(IV) oxide; In dichloromethane; at 25℃; for 48h;	2,3-Dichloro-5-formylpyridine. To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (64, 8.10 g, 50.0 mmol) in anhydrous CH2CIo ( 150 mL). The reaction mixture was stirred at a temperature of about 250C for 48 h, filtered through CELITE, and concentrated under reduced pressure. The mixture was chromatographed by a silica gel chromatography column eluting with a gradient of ethyl acetate (0%-40%)/hexanes to provide 7.2 g of 65 (90% yield). 1H NMR (400 MHz, CDCl3) delta 10.08 (IH, s), 8.77 (I H, d, J=1.97 Hz), 8.25 (IH, d, J=1.97 Hz). LC/MS (M+1 ): 176.
90%	With manganese(IV) oxide; In dichloromethane; at 20℃; for 48h;	To a 500 mL round-bottom flask, manganese oxide (43.5 g, 0.50 mol) was added to a solution of 2,3-dichloro-5-hydroxylmethylpyridine (1, 8.10 g, 50.0 mMol) in <n="70"/>anhydrous CH2Cl2 (150 mL). The resulting mixture was stirred at room temperature for 2 days, which was filtered through Celite and concentrated. The crude mixture was purified by a silica gel chromatography column eluting with a gradient of ethyl acetate (0-40%)/hexanes to give 7.2 g of the desired product 2 (90%). 1H NMR (400 MHz, CDCl3) delta 10.08 (1 H, s), 8.77 (1 H, d, J = 1.97 Hz), 8.25 (1 H, d, J = 1.97 Hz). LC/MS (M+l): 176.
88%	With Dess-Martin periodane; In dichloromethane; at 0℃; for 0.5h;Inert atmosphere;	To a solution of (5,6-dichloropyridin-3-yl)methanol (23) (1 g, 5.62 mmol) in CH2Cl2 (40 ml) was added Dess-Martin (2.6 g, 6.18 mmol) at 0 C. under nitrogen. (0747) After being stirred for 30 min at 0 C., the reaction mixture was quenched with sat. NaHCO3 and diluted with CH2Cl2. The resulting organic layer was separated and the aqueous layer was extracted with CH2Cl2, the combined organic layers were washed with Na2S2O3, H2O and brine, dried over Na2SO4 and concentrated in vacuo. The residue was triturated with CHCl3. The resulting solid was filtered through a glass funnel, rinsed with CHCl3. The liquid residue was chromatographed on silica gel eluting with a gradient of hexane/ethyl acetate (10-20%) to afford 867 mg of the desired product (24) in 88% yield as a white solid. 1H-NMR (DMSO-d6) delta: 10.09 (1H, s), 8.90 (1H, s), 8.55 (1H, s). LC/MS (M+1): 176.
22%		To a solution of (5,6-dichloro-3-pyridinyl)methanol (200 mg) in CH2Cl2, molecular sieves (3A) (55 mg) and 4-methy-morpholine-N-oxide (198 mg) was added and stirred at room temperature for 10 minutes. Then tetra-n-propylammonium perruthenate(VII) (38 mg) was added and stirred overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under vacuum. The residue obtained was purified by chromatography column on silica gel using a mixture of EtOAc/hexane as eluent to give 44 mg (22%) of the title compound. 1H-NMR (delta, ppm, CDCl3): 10.09 (s, 1 H), 8.77 (s, 1 H), 8.25 (s, 1 H).
22%		Preparation 2; 5,6-Dichloro-3-pyridinecarbaldehyde (Used to prepare Example 15) To a solution of (5,6-dichloro-3-pyridinyl)methanol (200 mg) in DCM, molecular sieves (3A) (55 mg) and 4-methyl-morpholine-N-oxide (198 mg) was added and stirred at room temperature for 10 minutes. Then tetra-n-propylammonium perruthenate (VII) (38 mg) was added and stirred overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under vacuum. The residue obtained was purified by chromatography column on silica gel using a mixture of EtOAc/hexane as eluent to give 44 mg (22%) of the title compound.1H-NMR (delta, ppm, CDCl3): 10.09 (s, 1H), 8.77 (s, 1H), 8.25 (s, 1H).
	With manganese(IV) oxide; In hexane; dichloromethane; at 20℃; for 1h;	Example 154 [(1S)-1- {5-CHLORO-6-[(3R)-3-METHYL-4-(5-TRIFLUOROMETHYL-LH-BENZOIMIDAZOL-2-YL)- PIPERAZIN-1-YL]-PYRIDIN-3-YL}-ETHANOL AND (1R)-1- {5-CHLORO-6- [ (3R)-3-METHYL-4- (5-TRIFLUOROMETHYL-LH-BENZOIMIDAZOL-2-YL)-PIPERAZIN-1-YL]-PYRIDIN-3-YL}-ETHANOL.] (a) 5, [6-DICHLORO-PYRIDINE-3-CARBALDEHYDE.] A mixture of (5,6-dichloro-pyridin-3-yl)-methanol (1.78 g, 10 mmol, TCI- US) and [MNO2] (17. [39G,] 200 mmol, Aldrich) in 1: 1 [CH2CL2/HEXANE] (10 mL) was stirred at room temperature for 1 h. The catalyst was filtered and washed with 50% EtOAc/hexane. The filtrate was evaporated and the residue dried in vacuo to give the title compound product, which was used in the next step without additional purification. MS (ESI, pos. ion) [M/Z] : 176 (M+1).
	With manganese(IV) oxide; In dichloromethane; at 20 - 25℃; for 96h;	2.50 Example 50 (Prepared according to Scheme 10); (2R)-4-(3-Chloro-5-(l-hydroxyethyl)pyridin-2-yl)-2-methyl-N-(4-(trimethylsilyl)phenyl)piperazine-l- carboxamide; A solution of (5,6-dichloropyridin-3-yl) methanol (5.62mmol) and manganese dioxide (52mmol) in DCM (50 ml) was stirred at room temperature for 4 days. The reaction was filtered through celite, washed with EtOH and concentrated under reduced pressure yielding the crude product which was used without purification, 5,6- dichloronictoninaldehyde. To a solution of the crude 5,6-dichloronictoninaldehyde (3.24mmol) in THF (20ml) at -78 0C was added methyl magnesium bromide (9.72mmol) in a dropwise fashion. The reaction was allowed to warm to room temperature overnight. The reaction was quenched with saturated ammonium chloride (50ml) and extracted with ethyl acetate (50 ml) The organic phase was separated, dried with a phase separation cartridge and concentrated under reduced pressure yielding the crude oil which was purified by flash chromatography (0-30% ethyl acetate in petroleum ether) yielding the product. l-(5,6-dichloropyridin- 3-yl)ethanol (2.14mmol).MS: ES+ 191.9. 1H NMR (400 MHz, CDCl3) delta 8.29 (s, IH), 7.75 - 8.03 (m, IH), 4.92 - 5.11 (m, IH), 2.11 - 2.26 (m, IH), 1.45 - 1.56 (m, 3H)The title compound was synthesised in accordance with Example 23 using (R)-(+)-2-methylpiperazine and the above intermediate l-(5,6-dichloropyridin-3-yl)ethanol.MS: ES+ 447.2. 1H NMR (400 MHz, CDCl3) delta 8.07 (s, IH), 7.60 (t, IH), 7.32 - 7.40 (m, 2H), 7.24 - 7.31 (m, 2H), 6.26 (s, IH), 4.74 - 4.85 (m, IH), 4.21 - 4.32 (m, IH), 3.76 - 3.88 (m, IH), 3.59 - 3.74 (m, 2H), 3.30 - 3.43 (m, IH), 2.93 - 3.04 (m, IH), 2.80 - 2.93 (m, IH), 1.71 - 1.77 (m, IH), 1.38 - 1.44 (m, 3H), 1.32 - 1.38 (m, 3H), 0.15 (s, 9H)
	With manganese(IV) oxide; In hexane; dichloromethane; for 1h;	The intermediate, ethyl (E)-3-{2-[3'-(l-adamantyl)-4'-hydroxyphenyl]-3-chloro-5- pyridinyl}-2-propenoate was prepared as follows.; a) Ethyl (£)-3-(5,6-Dichloro-2-pyridinyl)-2-propenoate.; A reported method(Ognyanov, V. I. et al., J. Med. Chem., 2006, 49, 3719-3742) was used to synthesize 2,3- dichloro-5-formylpyridine. A mixture of 5,6-dichloro-3-pyridinemethanol (1.42 g, 8.00 mmol) and Mn02 (13.9 g, 160 mmol) in 1 : 1 CH2Cl2/hexane (8 mL) was stirred for 1 h, then diluted with 50% EtOAc/hexane (20 mL), and filtered (50% EtOAc/hexane wash). The filtrate was evaporated, and the residue was dried in vacuo for use in the next step.

Reference： [1]Patent: US2010/120862,2010,A1 .Location in patent: Page/Page column 94
[2]Patent: US2010/137306,2010,A1 .Location in patent: Page/Page column 169
[3]Patent: US2010/130499,2010,A1 .Location in patent: Page/Page column 122
[4]Patent: WO2008/132600,2008,A2 .Location in patent: Page/Page column 258
[5]Patent: WO2008/133973,2008,A1 .Location in patent: Page/Page column 68-69
[6]Patent: US9156830,2015,B2 .Location in patent: Page/Page column 91-92
[7]Journal of Medicinal Chemistry,2006,vol. 49,p. 3719 - 3742
[8]Patent: EP2080761,2009,A1 .Location in patent: Page/Page column 39-40
[9]Patent: US2009/306089,2009,A1 .Location in patent: Page/Page column 25-26
[10]Patent: WO2004/35549,2004,A1 .Location in patent: Page 164
[11]Patent: WO2010/92342,2010,A1 .Location in patent: Page/Page column 48
[12]Patent: WO2011/79305,2011,A1 .Location in patent: Page/Page column 43
[13]Journal of Medicinal Chemistry,2011,vol. 54,p. 3793 - 3816

4
[ 71690-05-6 ]
[ 900184-06-7 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3719 - 3742

5
[ 71690-05-6 ]
[ 900184-17-0 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3719 - 3742

6
[ 71690-05-6 ]
(S)-1-(5-Chloro-6-{(R)-3-methyl-4-[6-trifluoromethyl-4-(3,4,5-trifluoro-phenyl)-1H-benzoimidazol-2-yl]-piperazin-1-yl}-pyridin-3-yl)-ethanol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3719 - 3742

7
[ 71690-05-6 ]
(R)-1-(5-Chloro-6-{(R)-3-methyl-4-[6-trifluoromethyl-4-(3,4,5-trifluoro-phenyl)-1H-benzoimidazol-2-yl]-piperazin-1-yl}-pyridin-3-yl)-ethanol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3719 - 3742

8
[ 71690-05-6 ]
[ 475288-18-7 ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 7381 - 7389

9
[ 71690-05-6 ]
(R)-1-(5,6-dichloropyridin-3-yl)but-3-en-1-ol [ No CAS ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 7381 - 7389

10
[ 71690-05-6 ]
[ 1026080-94-3 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

11
[ 71690-05-6 ]
N-Boc-3-amino-3-(5,6-dichloro-3-pyridyl)propionic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

12
[ 71690-05-6 ]
[ 297773-54-7 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

13
[ 71690-05-6 ]
[ 1026422-28-5 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

14
[ 71690-05-6 ]
(R)-3-[(S)-1-(5,6-Dichloro-pyridin-3-yl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

15
[ 71690-05-6 ]
(S)-3-(5,6-Dichloro-pyridin-3-yl)-3-[(R)-1-(3-piperidin-4-yl-propionyl)-piperidine-3-carbonyl]-amino}-propionic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

16
[ 71690-05-6 ]
4-(3-{(R)-3-[(S)-1-(5,6-Dichloro-pyridin-3-yl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

17
[ 71690-05-6 ]
4-(3-{(R)-3-[(S)-2-Carboxy-1-(5,6-dichloro-pyridin-3-yl)-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 5254 - 5265

18
[ 71690-05-6 ]
benzoic acid-(5,6-dichloro-[3]pyridylmethyl ester) [ No CAS ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1932,vol. <2>134,p. 177,184

19
2,3-dichloro-5-dichloromethyl-pyridine [ No CAS ]
[ 71690-05-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In water; ethyl acetate;	STR12 A mixture of 2.5 g (0.0108 mol) of 2,3-dichloro-5-dichloromethyl-pyridine and 20 ml of water is heated to reflux. The pH is kept between 4 and 7 by adding a saturated sodium hydrogencarbonate solution dropwise. After 6 hours, the mixture is cooled, extracted using ethyl acetate and the solvent is carefully removed from the organic phase by distillation in a water jet vacuum. 1.4 g (73% of theory) of 5,6-dichloro-nicotinaldehyde of melting point 65 C. are obtained.

Reference： [1]Patent: US5051513,1991,A

Yield	Reaction Conditions	Operation in experiment
		13(4) 5,6-Dichloropyridyl-3-carboxaldehyde 1H-NMR (300 MHz, CDCl3delta TMS): 8.21 (d, J = 1 Hz, 1 H), 8.74 (d, J = 1 Hz, 1 H), 10.05 (s, 1 H).

21
[ 71690-05-6 ]
[ 5927-18-4 ]
[ 955029-08-0 ]

Yield	Reaction Conditions	Operation in experiment
		2) To a solution of methyl (dimethoxyphosphoryl) acetate (3.4mL) in toluene (103mL) was added portionwise 60% NaH (0.96g) at 20 to 300C under nitrogen atmosphere and the mixture was stirred at the same temperature for 30 minutes. To the mixture was added dropwise above Solution A at 0 to 100C and the mixture was stirred at ambient temperature for 1 hour. The reaction mixture was poured into a mixture of AcOEt and water and adjusted to pH 2 with IN- HCl aq. The separated organic layer was washed with saturated sodium hydrogen carbonate aq., dried over magnesium sulfate and evaporated in vacuo. The residue was triturated with IPE to give methyl (2E) -3- (5, 6-dichloropyridin-3-yl) acrylate (2.83g).

Reference： [1]Patent: WO2008/75757,2008,A1 .Location in patent: Page/Page column 36

22
[ 162327-73-3 ]
[ 71690-05-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With lithium aluminium tetrahydride; In tetrahydrofuran; at -78℃; for 0.5h;	A 2M solution of LiAIH4 in THF (1 9.2mL, 38.2gmmol) was added to a solution of 5,6-dichloro-N-methoxy-N-methylnicotinamide (22g, 76.59mo1) in THE (360mL) at -78C and stirred for 30 mm at sametemperature. The RM was quenched with sat. Na2SO4 solution and filtered the salts through celite bed, washed with EtOAc. The filtrate was dried (anhydr. Na2SO4), filtered and evaporated the solvent under vacuo to give crude as a thick liquid. The crude was purified by CC (0-5% EtOAc in PE) to give 12g (75%) of 5,6-dichloronicotinaldehyde as liquid.
	With diisobutylaluminium hydride; In toluene; at -30℃; for 0.5h;	Preparation 2331) To a solution of 5, 6-dichloro-N-methoxy-N- methylnicotinamide (4.7g) in toluene (141.OmL) was added dropwise a solution of 0.99M diisobutylaluminium hydride solution of toluene (22.2mL) at -300C under nitrogen atmosphere and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was quenched with MeOH (4.ImL) and stirred at 00C for 30 minutes. (Solution A)

Reference： [1]Patent: WO2015/158427,2015,A1 .Location in patent: Page/Page column 90; 91
[2]Patent: WO2008/75757,2008,A1 .Location in patent: Page/Page column 36

23
[ 71690-05-6 ]
[ 1779-49-3 ]
[ 1001193-62-9 ]

Yield	Reaction Conditions	Operation in experiment
70%		To a stirred slurry of methyltriphenylphosphonium bromide (10.0 g) in toluene (200 mL) at 0 C. was added potassium t-butoxide (3.07 g) portionwise to produce a yellow slurry. After 1 hr, the reaction mixture was cooled to -20 C. and 4 (4.0 grams, 22.72 mmol) dissolved in tetrahydrofuran (6 mL) was added dropwise to produce a purple colored slurry. The reaction mixture was heated to 0 C. and stirred for an additional 1 hr. Then the reaction mixture was treated with saturated aqueous brine (150 mL) and diluted with ethyl acetate (200 mL). The resulting organic portion was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting product was chromatographed by silica gel chromatography column eluting with a gradient of ethyl acetate (0%-10%)/hexanes to provide 2.77 g of 1 (70% yield). 1H NMR (400 MHz, CDCl3) delta 8:30 (1H, d, J=2.19 Hz), 7.80 (1H, d, J=2.19 Hz), 6.63 (1H, dd, J=10.96, 17.80 Hz), 5.86 (1H, d, J=17.80 Hz), 5.45 (1H, d, J=10.96 Hz). LC/MS (M+1): 174.
70%		To a stirred slurry of methyltriphenylphosphonium bromide (10.0 g) in toluene (200 mL) at 0 C. was added potassium t-butoxide (3.07 g) portionwise to produce a yellow slurry. After 1 hr, the reaction mixture was cooled to -20 C. and 4 (4.0 grams, 22.72 mmol) dissolved in tetrahydrofuran (6 mL) was added dropwise to produce a purple colored slurry. The reaction mixture was heated to 0 C. and stirred for an additional 1 hr. Then the reaction mixture was treated with saturated aqueous brine (150 mL) and diluted with ethyl acetate (200 mL). The resulting organic portion was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting product was chromatographed by silica gel chromatography column eluting with a gradient of ethyl acetate (0%-10%)/hexanes to provide 2.77 g of 1 (70% yield). 1H NMR (400 MHz, CDCl3) delta 8.30 (1H, d, J=2.19 Hz), 7.80 (1H, d, J=2.19 Hz), 6.63 (1H, dd, J=10.96, 17.80 Hz), 5.86 (1H, d, J=17.80 Hz), 5.45 (1H, d, J=10.96 Hz). LC/MS (M+1): 174.
70%		To a stirred slurry of methyltriphenylphosphonium bromide (10.0 g) in toluene (200 mL) at 0 C. was added potassium t-butoxide (3.07 g) portionwise to produce a yellow slurry. After 1 hr, the reaction mixture was cooled to -20 C. and 4 (4.0 grams, 22.72 mmol) dissolved in tetrahydrofuran (6 mL) was added dropwise to produce a purple colored slurry. The reaction mixture was heated to 0 C. and stirred for an additional 1 hr. Then the reaction mixture was treated with saturated aqueous brine (150 mL) and diluted with ethyl acetate (200 mL). The resulting organic portion was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting product was chromatographed by silica gel chromatography column eluting with a gradient of ethyl acetate (0%-10%)/hexanes to provide 2.77 g of 1 (70% yield). 1H NMR (400 MHz, CDCl3) delta 8.30 (1H, d, J=2.19 Hz), 7.80 (1H, d, J=2.19 Hz), 6.63 (1H, dd, J=10.96, 17.80 Hz), 5.86 (1H, d, J=17.80 Hz), 5.45 (1H, d, J=10.96 Hz). LC/MS (M+1): 174.

70%		2,3-Dichloro-5-vinylpyridine. To a stirred slurry of methyltriphenylphosphonium bromide (10.0 g) in toluene (200 mL) at O0C was added potassium /-butoxide (3.07 g) portionwise to produce a yellow slurry. After 1 hr, the reaction mixture was cooled to -2O0C and 65 (4.0 grams, 22.72 mmol) dissolved in tetrahydrofuran (6 mL) was added dropwise to produce a purple colored slurry. The reaction mixture was heated to O0C and stirred for additional 1 hr. Then the reaction mixture was treated with saturated aqueous brine ( 150 mL) and diluted with ethyl acetate (200 mL). The resulting organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting product was chromatographed by silica gel chromatography column eluting with a gradient of ethyl acetate (0%-10%)/hexanes to provide 2.77 g of 66 (70% yield). 1H NMR (400 MHz, CDCl3) delta 8.30 (IH, d, J=2.19Hz), 7.80 (IH, d, J=2.19Hz), 6.63 (IH, dd, J=10.96, 17.80Hz), 5.86 (IH, d, J=17.80Hz), 5.45 (IH, d, J=10.96Hz). LC/MS (M+l ): 174.
70%		To a cooled 0C, stirred slurry of methyltriphenylphosphonium bromide (10.0 g) in toluene (200 mL) was added potassium t-butoxide (3.07 g) portionwise to produce a yellow slurry. After 1 hr, the reaction mixture was cooled to -20C and 2,3-dichloro-5- formylpyridine (2, 4.0 grams, 22.72 mMol) which dissolved in tetrahydrofuran (6 mL) was added dropwise to produce a purple colored slurry. The reaction mixture was warmed to 0C and stirred for additional 1 hr. Then the reaction mixture was treated with saturated aqueous brine (150 mL) and diluted with ethyl acetate (200 mL). The resulting organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by silica gel chromatography column eluting with a gradient of ethyl acetate (0-10%)/hexanes to afford 2.77 g of the desired product 3 (70%). 1H NMR (400 MHz, CDCl3) delta 8.30 (1 H, d, J = 2.19 Hz), 7.80 (1 H, d, J = 2.19 Hz), 6.63 (1 H, dd, J = 10.96, 17.80 Hz), 5.86 (1 H, d, J = 17.80 Hz), 5.45 (1 H, d, J = 10.96 Hz). LC/MS (M+l): 174.
64%		2,3-dichloro-5-vinylpyridine. To a suspension of methyltriphenylphosphonium bromide (PPh3CH3Br, 7.08 g, 19.8 mmol, Sigma-Aldrich) in THF (40 mL) at O0C was added dropwise a 0.5N solution of potassium bis(trimethylsilyl)amide [K(N(TMS)2)]in toluene (39.6 mL, 19.8 mmol, Sigma-Aldrich). Then the resultant mixture was stirred at 00C for lhour. To the mixture was added a solution of 65 (3.17g, 18.0 mmol) in THF (20 mL) at 00C. The reaction mixture was stirred for 2 h at O0C. The reaction was quenched with water, and the mixture was extracted three times with EtOAc (150 mL for each extraction). The organic portions were combined, washed with brine, and concentrated to dryness. Compound 66 was obtained as a slight yellowish oil via flash chromatography using ethyl acetate/hexane gradient as an eluent (64% yield). 1H NMR: (CDCl3) delta 8.28 (d, J=2.1 Hz, I H), 7.82 (d, J=2.2 Hz, I H), 6.65 (dd, J=I 1.0, 17.5 Hz, I H), 5.85 (d, J=17.5 Hz, I H), 5.48 (d, J=I LO Hz, l H) ppm.

24
[ 71690-05-6 ]
[ 3144-09-0 ]
2,3-dichloro-5-methylsulfonamidomethylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium tris(acetoxy)borohydride; acetic acid; triethylamine; In dichloromethane; at 0 - 25℃; for 15h;	2,3-dichloro-5-methylsulfonamidylmethyl pyridine. To a suspension of methyl sulfonamide (1.08 g, 1 1.35 mmol), 2,3-dichloropyridinyl aldehyde, (79, 3.0 g, 17.03 mmol), AcOH (1.35 mL), and NaBH(OAc)3 in dry dichloromethane (70 mL) at O0C, TEA (3.18 mL, 22.7 mmol) was added. The reaction mixture was heated to a temperature of about 250C and stirred for 15 h. Thereafter, saturated NaHCO3 (2 mL) was added. The mixture was extracted twice with ethyl acetate (8OmL for each extraction). The organic portions were combined, washed twice with brine (5OmL for each wash), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The oily residue was chromatographed using a COMBIFLASH apparatus with a 40 g REDISEP column with eluent of 40% ethyl acetate in hexanes to provide 2.8 g of 105 (65% yield) and 20% recovered starting material. 1H NMR (CDCl3): delta 8.38 (s, IH), 8.27 (s, IH), 5.03 (bs, NH), 4.35 (d, J=17Hz, 2H), 3.0 (s, 3H).

Reference： [1]Patent: WO2008/132600,2008,A2 .Location in patent: Page/Page column 293

25
[ 71690-05-6 ]
[ 1308279-83-5 ]

Reference： [1]Patent: WO2011/79305,2011,A1

26
[ 71690-05-6 ]
[ 1308279-77-7 ]

Reference： [1]Patent: WO2011/79305,2011,A1

27
[ 71690-05-6 ]
[ 1308279-71-1 ]

Reference： [1]Patent: WO2011/79305,2011,A1

28
[ 71690-05-6 ]
[ 1099-45-2 ]
[ 1308279-67-5 ]

Yield	Reaction Conditions	Operation in experiment
	In toluene;Reflux;	A solution of crude <strong>[71690-05-6]2,3-dichloro-5-formylpyridine</strong> and(carbethoxymethylene)triphenylphosphorane (2.14 g, 5.83 mmol) in toluene (12 mL) was heated at reflux overnight and then cooled to room temperature. After solvent removal at reduced pressure, the residue was chromatographed (9% to 10% EtOAc/hexane) to give 323 mg (16%) from 5,6-dichloro-3-pyridinemethanol) of ethyl (E)-3-(5,6-dichloro-2-pyridinyl)-2- propenoate as a white solid, mp 102-103 C. IR 2914, 1702, 1428, 1193 cm"1; 1H NMR (CDC13) delta 1.37 (t, J= 7.2 Hz, 3H, OCH2CHj), 4.31 (q, J= 7.2 Hz, 2H, OCH2CH3), 6.53 (d, J = 16.2 Hz, 1H, CH=CHCO), 7.62 (d, J= 16.2 Hz, 1H, CH=CHCO), 7.94 (d, J= 1.8 Hz, 1H, 4-ArH), 8.44 ppm (d, J= 1.8 Hz, 1H, 2-ArH). HRMS calcd C10H9Cl2NO2 [M + H]+ 246.0083, found 246.0086.

Reference： [1]Patent: WO2011/79305,2011,A1 .Location in patent: Page/Page column 43

29
[ 71690-05-6 ]
[ 1099-45-2 ]
[ 1313052-99-1 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 3793 - 3816

30
[ 71690-05-6 ]
[ 261625-62-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With hydroxylamine hydrochloride; sodium acetate; In ethanol; for 3h;Inert atmosphere; Reflux;	To a solution of (24) (866 mg, 4.92 mmol) in EtOH (16 ml) were added NH2OH HCl (581 mg, 8.36 mmol) and NaOAc (848 mg, 10.3 mmol) at room temperature under nitrogen. After being stirred for 3 hrs at reflux temperature, the reaction mixture was poured into H2O and filtered through glass fiber paper. The resulting solid was re-dissolved in CH2Cl2 and the solution was dried over Na2SO4 and concentrated in vacuo. The residue was triturated with hexane. The resulting solid was filtered through a glass funnel, rinsed with hexane, and collected to afford 681 mg of the desired product (25) in 72% yield as a white solid. 1H-NMR (DMSO-d6) delta: 11.85 (1H, s), 8.59 (1H, s), 8.26 (1H, s), 8.21 (1H, s). LC/MS (M+1): 191.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3001 - 3006
[2]Patent: US9156830,2015,B2 .Location in patent: Page/Page column 92

31
[ 71690-05-6 ]
[ 950482-85-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3001 - 3006

32
[ 71690-05-6 ]
[ 943137-86-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3001 - 3006

33
[ 71690-05-6 ]
C₁₃H₁₆Cl₂N₂O₄*C₁₀H₁₅NO [ No CAS ]

Reference： [1]Organic Process Research and Development,2001,vol. 5,p. 23 - 27

34
[ 71690-05-6 ]
[ 1001193-62-9 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

35
[ 71690-05-6 ]
[ 1073617-83-0 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794
[2]Patent: WO2008/132600,2008,A2

36
[ 71690-05-6 ]
[ 1073617-84-1 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794
[2]Patent: WO2008/132600,2008,A2

37
[ 71690-05-6 ]
[ 1073617-85-2 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794
[2]Patent: WO2008/132600,2008,A2

38
[ 71690-05-6 ]
(R)-3-chloro-5-(1,2-dihydroxyethyl)-3',6'-dihydro-2'H-[2,4']-bipyridinyl-1'-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

39
[ 71690-05-6 ]
(S)-1-(3-chloro-1′2',3',6'-tetrahydro-[2,4']bipyridinyl-5-yl)ethane-1,2-diol hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

40
[ 71690-05-6 ]
[ 1074021-63-8 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

41
[ 71690-05-6 ]
[ 1073616-24-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794
[2]Patent: WO2008/132600,2008,A2

42
[ 71690-05-6 ]
[ 1073617-14-7 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

43
[ 71690-05-6 ]
[ 1073616-61-1 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

44
[ 71690-05-6 ]
(S)-4-[3-chloro-5-(1,2-dihydroxyethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-3,6-dihydropyridine-1(2H)-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

45
[ 71690-05-6 ]
[ 1073616-42-8 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6781 - 6794

46
[ 71690-05-6 ]
C₁₉H₂₁N₅OS [ No CAS ]