[ CAS No. 175461-33-3 ] {[proInfo.proName]}

Name: 175461-33-3|2,6-Dichloro-N-methylpyridin-4-amine|97%
Brand: Ambeed
SKU: A130367
Price: 27.0 USD
Availability: InStock
Rating: 93 (32 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 175461-33-3

Structure of 175461-33-3 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 175461-33-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 175461-33-3 ]

SDS Specification

Alternatived Products of [ 175461-33-3 ]

Product Details of [ 175461-33-3 ]

CAS No. :	175461-33-3	MDL No. :	MFCD12024871
Formula :	C₆H₆Cl₂N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ITRDWZKFGCLLTO-UHFFFAOYSA-N
M.W :	177.03	Pubchem ID :	19957394
Synonyms :

Calculated chemistry of [ 175461-33-3 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.56
TPSA :	24.92 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) :	-5.93 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.9
Log Po/w (XLOGP3) :	2.04
Log Po/w (WLOGP) :	2.24
Log Po/w (MLOGP) :	1.36
Log Po/w (SILICOS-IT) :	2.31
Consensus Log Po/w :	1.97

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.6
Solubility :	0.444 mg/ml ; 0.00251 mol/l
Class :	Soluble
Log S (Ali) :	-2.19
Solubility :	1.14 mg/ml ; 0.00644 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.69
Solubility :	0.0359 mg/ml ; 0.000203 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.55

Safety of [ 175461-33-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 175461-33-3 ]

* 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 [ 175461-33-3 ]
Downstream synthetic route of [ 175461-33-3 ]

[ 175461-33-3 ] Synthesis Path-Upstream 1~4

1
[ 16063-69-7 ]
[ 74-89-5 ]
[ 175461-33-3 ]

Yield	Reaction Conditions	Operation in experiment
61%	at 20℃; for 336 h;	2,4,6-Trichloropyridine (20.0 g, 190.63 mmol) was dissolved ethanol (100 mL). Methyl amine (33percent wt in ethanol, 81.9 mL, 657 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 2 weeks. The white precipitate was filtered off and washed with te/t-butylmethylester and water to give (2,6-dichloro- pyhdin-4-yl)-methylamine (11.9 g, 61 percent) as a white crystalline compound.
51%	at 55 - 60℃; for 24 h;	A1.6: 2,6-Dichloro-4-methylamino-pyridine57 EPO <DP n="59"/> A1.6An 8M solution of methylamine in ethanol (5 ml; 40 mmol) was added drop wise to a stirred solution of 2,4,6-trichloropyridine (5 g; 27.4 mmol) in absolute ethanol (50 ml). After heating to 55-60° C. for 24 hr, the mixture was cooled to rt and concentrated. After adding water (50 ml) to the residue, the resulting suspension was filtered and the white filter cake was washed with water (3 x 10 ml). After air drying, the solid was suspended in dichloromethane (25 ml) and stirred for 10 minutes. Filtration, rinsing with dichloromethane and drying afforded 2.45 g (51percent) of A1.6 as a white solid. HPLC (A): 95percent, ret. time = 1.16 min., LC/MS (M+H)⁺ = 177.00 (178.99).
51%	at 20 - 60℃; for 1.66 - 24 h;	Methylamine (8M solution in ethanol, 5 ml; 40 mmol) was added drop wise to a stirred solution of commercially available 2,4,6-trichloropyridine (5 g; 27.4 mmol) EPO <DP n="73"/>in absolute ethanol (50 ml). After heating to 55-60° C. for 24 hr, the mixture was cooled to rt and concentrated. After adding water (50 ml) to the residue, the resulting suspension was filtered and the white filter cake was washed with water (3 x 10 ml). After air drying, the solid was suspended in dichloromethane (25 ml) and stirred for 10 minutes. Filtration, rinsing with dichloromethane and drying afforded 2.45 g (51percent) of A1.6 as a white solid. HPLC (A): 95percent, ret. time = 1.16 min., LC/MS(M+H)⁺ = 177.00 (178.99). Alternate preparation:2,4,6-Trichloropyridine (1800g, 9.89 mol) was dissolved in ethanol (1800 mL). Methylamine 40percent solution in ethanol (6.3 L) was added over Ih and 40min maintaining the reaction temperature between 20-25 ⁰C. The reaction was stirred for14 hours at room temperature and concentrated. The product was filtered, washed with methyl t-butyl ether (1 ,500ml) and dried to yield A1.6 (1200 g, 68percent)

36%	With caesium carbonate In tetrahydrofuran; ethanol at 55℃;	General procedure: To a solution ofnitrogen-containing nucleophile (1 eq.) and cesium carbonate (3.0 eq.) inN,N-dimethylformamide (2 mL/mmol) was added 2-haloheterocycle (1.1 eq.). Thereaction was heated to 100° C. and stirred at this temperature for 2 hours. Thereaction was then cooled to room temperature and acidified to pH=1 with 10percentaqueous HCl solution if product contains a carboxylic acid, or diluted withwater if neutral. The solution was extracted with twice with dichloromethane.The organic layers were combined, dried with sodium sulfate and concentratedunder vacuum. The crude material was either used directly in subsequentreactions or purified by flash chromatography.
36%	at 55℃;	General procedure: Similar to as described in General Procedure A, 2,4,6-trichloropyridine was reacted with methyl amine to give the title compound (700 mg, 36percent) as a white solid. LC-MS (ES, mlz): 177 [M+H]. To a solution of nitrogen-containing nucleophile (1 eq.) and cesium carbonate (3.0 eq.) in N,N-dimethylformamide (2 mL/mmol) was added 2-haloheterocycle (1.1 eq.). The reaction washeated to 100 °C and stirred at this temperature for 2 hours. The reaction was then cooled to room temperature and acidified to pH = 1 with 10 percent aqueous HCl solution if product contains a carboxylic acid, or diluted with water if neutral. The solution was extracted with twice with dichloromethane. The organic layers were combined, dried with sodium sulfate and concentrated under vacuum. The crude material was either used directly in subsequent reactions or purified byflash chromatography.

Reference： [1] Patent: WO2008/92942, 2008, A2, . Location in patent: Page/Page column 22
[2] Patent: WO2006/53166, 2006, A1, . Location in patent: Page/Page column 57-58
[3] New Journal of Chemistry, 2016, vol. 40, # 11, p. 9194 - 9204
[4] Patent: WO2006/122137, 2006, A1, . Location in patent: Page/Page column 71-72
[5] Patent: US2015/57260, 2015, A1, . Location in patent: Paragraph 0300; 0331; 0551; 0552
[6] Patent: WO2015/25026, 2015, A1, . Location in patent: Page/Page column 91; 137; 138
[7] Patent: WO2017/12647, 2017, A1, . Location in patent: Paragraph 0476

2
[ 2402-78-0 ]
[ 175461-33-3 ]

Reference： [1] New Journal of Chemistry, 2016, vol. 40, # 11, p. 9194 - 9204

3
[ 2587-00-0 ]
[ 175461-33-3 ]

Reference： [1] New Journal of Chemistry, 2016, vol. 40, # 11, p. 9194 - 9204

4
[ 175461-33-3 ]
[ 887147-19-5 ]

Reference： [1] Patent: US2015/57260, 2015, A1,
[2] Patent: WO2015/25026, 2015, A1,
[3] New Journal of Chemistry, 2016, vol. 40, # 11, p. 9194 - 9204
[4] Patent: WO2006/122137, 2006, A1,
[5] Patent: WO2006/122137, 2006, A1,

[ 175461-33-3 ] Synthesis Path-Downstream 1~88

1
[ 71637-34-8 ]
[ 175461-33-3 ]
[ 175461-24-2 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; mineral oil;	(1) Synthesis of an intermediate, 2-chloro-4-methylamino-6-(3-thienylmethyloxy)pyridine To a solution of 3-thiophenemethanol (1.42 g, 0.01131.1 mol) in 20 ml of dry tetrahydrofuran, sodium hydride (1.35 g (ca.60% in mineral oil), 0.01133.0 mol) was added. After the bubbling ceased, a solution of <strong>[175461-33-3]2,6-dichloro-4-methylaminopyridine</strong> (2.0 g, 0.0113 mol) in 30 ml of dry tetrahydrofuran was added dropwise at room temperature. After the addition, the reaction solution was stirred for about 20 hours under reflux. Then, the solvent was distilled off and the residue was partitioned between ethyl acetate and water. The obtained organic layer was washed successively with aqueous saturated sodium hydrogen carbonate and aqueous saturated sodium chloride, then dried over anhydrous sodium sulfate. After the solvent was distilled off, the residue was purified on a silica gel column to obtain the end product. Yield: 0.45 g (16%). Oily product. 1 H-NMR (60 MHz, CDCl3, delta): 2.64(3H,d,J=5 Hz), 4.2(1H,q, J=5 Hz), 5.2(2H,s), 5.6(1H,d,J=2 Hz), 6.0(1H,d,J=2 Hz), 6.9-7.3(3H, complex).

Reference： [1]Patent: US5624942,1997,A

2
[ 16063-69-7 ]
[ 74-89-5 ]
[ 175461-33-3 ]

Yield	Reaction Conditions	Operation in experiment
61%	In ethanol; at 20℃; for 336h;	2,4,6-Trichloropyridine (20.0 g, 190.63 mmol) was dissolved ethanol (100 mL). Methyl amine (33% wt in ethanol, 81.9 mL, 657 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 2 weeks. The white precipitate was filtered off and washed with te/t-butylmethylester and water to give (2,6-dichloro- pyhdin-4-yl)-methylamine (11.9 g, 61 %) as a white crystalline compound.
51%	In ethanol; at 55 - 60℃; for 24h;	A1.6: 2,6-Dichloro-4-methylamino-pyridine57 EPO <DP n="59"/> A1.6An 8M solution of methylamine in ethanol (5 ml; 40 mmol) was added drop wise to a stirred solution of 2,4,6-trichloropyridine (5 g; 27.4 mmol) in absolute ethanol (50 ml). After heating to 55-60 C. for 24 hr, the mixture was cooled to rt and concentrated. After adding water (50 ml) to the residue, the resulting suspension was filtered and the white filter cake was washed with water (3 x 10 ml). After air drying, the solid was suspended in dichloromethane (25 ml) and stirred for 10 minutes. Filtration, rinsing with dichloromethane and drying afforded 2.45 g (51%) of A1.6 as a white solid. HPLC (A): 95%, ret. time = 1.16 min., LC/MS (M+H)+ = 177.00 (178.99).
51 - 68%	In ethanol; at 20 - 60℃; for 1.66 - 24h;Product distribution / selectivity;	Methylamine (8M solution in ethanol, 5 ml; 40 mmol) was added drop wise to a stirred solution of commercially available 2,4,6-trichloropyridine (5 g; 27.4 mmol) EPO <DP n="73"/>in absolute ethanol (50 ml). After heating to 55-60 C. for 24 hr, the mixture was cooled to rt and concentrated. After adding water (50 ml) to the residue, the resulting suspension was filtered and the white filter cake was washed with water (3 x 10 ml). After air drying, the solid was suspended in dichloromethane (25 ml) and stirred for 10 minutes. Filtration, rinsing with dichloromethane and drying afforded 2.45 g (51%) of A1.6 as a white solid. HPLC (A): 95%, ret. time = 1.16 min., LC/MS(M+H)+ = 177.00 (178.99). Alternate preparation:2,4,6-Trichloropyridine (1800g, 9.89 mol) was dissolved in ethanol (1800 mL). Methylamine 40% solution in ethanol (6.3 L) was added over Ih and 40min maintaining the reaction temperature between 20-25 0C. The reaction was stirred for14 hours at room temperature and concentrated. The product was filtered, washed with methyl t-butyl ether (1 ,500ml) and dried to yield A1.6 (1200 g, 68%)

36%	With caesium carbonate; In tetrahydrofuran; ethanol; at 55℃;	General procedure: To a solution ofnitrogen-containing nucleophile (1 eq.) and cesium carbonate (3.0 eq.) inN,N-dimethylformamide (2 mL/mmol) was added 2-haloheterocycle (1.1 eq.). Thereaction was heated to 100 C. and stirred at this temperature for 2 hours. Thereaction was then cooled to room temperature and acidified to pH=1 with 10%aqueous HCl solution if product contains a carboxylic acid, or diluted withwater if neutral. The solution was extracted with twice with dichloromethane.The organic layers were combined, dried with sodium sulfate and concentratedunder vacuum. The crude material was either used directly in subsequentreactions or purified by flash chromatography.
36%	In tetrahydrofuran; ethanol; at 55℃;	General procedure: Similar to as described in General Procedure A, 2,4,6-trichloropyridine was reacted with methyl amine to give the title compound (700 mg, 36%) as a white solid. LC-MS (ES, mlz): 177 [M+H]. To a solution of nitrogen-containing nucleophile (1 eq.) and cesium carbonate (3.0 eq.) in N,N-dimethylformamide (2 mL/mmol) was added 2-haloheterocycle (1.1 eq.). The reaction washeated to 100 C and stirred at this temperature for 2 hours. The reaction was then cooled to room temperature and acidified to pH = 1 with 10 % aqueous HCl solution if product contains a carboxylic acid, or diluted with water if neutral. The solution was extracted with twice with dichloromethane. The organic layers were combined, dried with sodium sulfate and concentrated under vacuum. The crude material was either used directly in subsequent reactions or purified byflash chromatography.
	In ethanol; at 20℃; for 24h;	3.68. Compound 69: (lR,2R)-N-( 6-(2-ethyl-4-fluorophenox )-l-methyl-lH-imidazo[4, 5-c]pyridin-4- 3.68.1. Step i: 2,6-dichloro-N-methylpyridin-4-amine 33% v/v MeNH2 solution in EtOH (101 mL) is added dropwise to a suspension of 2,4,6- trichloropyridine (25 g) in EtOH (25 mL). The mixture is stirred at room temperature for 24 h. The mixture is concentrated and the residue is treated with DIPE. The precipitated desired product is filtered off and dried under vacuum.

Reference： [1]Patent: WO2008/92942,2008,A2 .Location in patent: Page/Page column 22
[2]Patent: WO2006/53166,2006,A1 .Location in patent: Page/Page column 57-58
[3]New Journal of Chemistry,2016,vol. 40,p. 9194 - 9204
[4]Patent: WO2006/122137,2006,A1 .Location in patent: Page/Page column 71-72
[5]Patent: US2015/57260,2015,A1 .Location in patent: Paragraph 0300; 0331; 0551; 0552
[6]Patent: WO2015/25026,2015,A1 .Location in patent: Page/Page column 91; 137; 138
[7]Patent: WO2017/12647,2017,A1 .Location in patent: Paragraph 0476

3
[ 175461-33-3 ]
[ 887147-20-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sulfuric acid; nitric acid; at 0℃; for 1h;	Into a 25-mL round-bottom flask was placed <strong>[175461-33-3]2,6-dichloro-N-methylpyridin-4-amine</strong> (600 mg, 3.39 mmol, 1.00 equiv), nitric acid (1 mL, 22.30 mmol, 6.58 equiv), and sulfuric acid (5 mL, 93.80 mmol, 27.68 equiv) at 0 C. After 1 h the resulting solution was mixed with ice/water, extracted with ethyl acetate, and washed with aqueous sodium carbonate and brine. The organic was concentrated under vacuum and the residue was dissolved in 5 mL of sulfuric acid. The resulting solution was stirred overnight at room temperature and poured slowly into 10 mL of ice/water. The solids were collected by filtration. This resulted in the title compound (600 mg, 80%) as a yellow solid. LC-MS (ES, m/z): 222 [M+H]+.
80%	With sulfuric acid; nitric acid; at 0℃; for 1h;	Into a 25-mL round-bottom flask was placed <strong>[175461-33-3]2,6-dichloro-N-methylpyridin-4-amine</strong> (600 mg, 3.39 mmol, 1.00 equiv), nitric acid (1 mL, 22.30 mmol, 6.58 equiv), and sulfuric acid (5 mL, 93.80 mmol, 27.68 equiv) at 0 C. After 1 h the resulting solution was mixed with ice/water, extracted with ethyl acetate, and washed with aqueous sodium carbonate and brine. The organic wasconcentrated under vacuum and the residue was dissolved in 5 mL of sulfuric acid. The resulting solution was stirred overnight at room temperature and poured slowly into 10 mL of ice/water. The solids were collected by filtration. This resulted in the title compound (600 mg, 80%) as a yellow solid. LC-MS (ES, m/z): 222 [M+H].
76%	With sulfuric acid; nitric acid; at 0℃; for 1h;	Sulfuric acid (60 mL) was cooled to 0 0C and (2,6-dichloro-pyridin-4-yl)- methylamine (11.9 g, 62.51 mmol) was added. Nitric acid (2.59 mL, 62.51 mmol) was added dropwise. The resulting yellow solution was stirred at 00C for 1 hour. The <n="24"/>reaction mixture was poured into ice water (600 ml_). Ethyl acetate was added and the phases separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with aqueous sodium carbonate, dried over magnesium sulphate, filtrated and evaporated to give a yellow solid. The solid was redissolved in sulfuric acid poured into ice water (500 ml_). The resulting solid was filtered off and washed with water to give (2,6-dichloro-3-nitro-pyridin-4-yl)-methyl- amine (10.5 g, 76%) as a yellow crystalline compound.

49%	With sulfuric acid; nitric acid; at 0 - 6℃; for 0.916667h;	Al .7 : 2 ,6-Dichloro-4-methylamino- 3-nitro-pyridinec; A1.7Solid A1.6 (3.5 g, 19 mmol) was added portionwise to stirred concentrated sulfuric acid at 0 C. Effervescence was observed. 90% Fuming nitric acid (3.5 ml) was added drop wise at a rate that maintained the internal temperature below 6 C. After the addition was complete (45 minutes), the solution was stirred 10 minutes. The reaction mixture was poured onto ~100 g of ice and the resulting aqueous mixture was extracted with dichloromethane (3 x 100 ml). The combined organics were washed with water (200 ml), dried (MgSO4ZNa2SO4) and concentrated. The residue was dissolved in concentrated sulfuric acid (25 ml) and stirred 30 minutes at rt. Pouring the reaction mixture into ice gave a yellow suspension that was filter and58 EPO <DP n="60"/>dried to afford 2.45 g (49%) of A1.7 as a yellow solid. HPLC (A): 95%, ret. time = 1.16 min., LC/MS (M+H)+ = 177.00 (178.99).
49%	With sulfuric acid; nitric acid; at 0 - 6℃; for 0.916667h;Product distribution / selectivity;	Solid A1.6 (3.5 g, 19 rnmol) was added portionwise to stirred concentrated sulfuric acid at 0 C. Effervescence was observed. 90% Fuming nitric acid (3.5 ml) was added drop wise at a rate that maintained the internal temperature below 6 C. After the addition was complete (45 minutes), the solution was stirred 10 minutes. The reaction mixture was poured onto ~100 g of ice and the resulting aqueous mixture was extracted with dichloromethane (3 x 100 ml). The combined organics were washed with water (200 ml), dried (MgSO4/Na2SO4) and concentrated. The residue was dissolved in concentrated sulfuric acid (25 ml) and stirred 30 minutes at rt. Pouring the reaction mixture into ice gave a yellow suspension that was filter and dried to afford 2.45 g (49%) of A1.7 as a yellow solid. HPLC (A): 95%, ret. time =1.16 rnin., LC/MS (M+H)+ = 177.00 (178.99).
		3.68.2. Step U: 2,6-dichloro-N-methyl-3-nitropyridin-4-amine <strong>[175461-33-3]2,6-dichloro-N-methylpyridin-4-amine</strong> (19.3 g) is added in portions to cone. H2SO4 (40 mL) at 0 C. After 5 min fuming HNO3 (19 mL) is added dropwise over 5 min at 0 C. The mixture is stirred at 0 C for 1 h. The mixture is poured in icy water and extracted with DCM. The organic layer is dried and concentrated. The residue is dissolved in precooled (0 C) cone. H2SO4 (18 mL) and the mixture is stirred for 1.5 h at 0 C. The mixture is poured in icy water and extracted with DCM. The organic layer is dried and concentrated. NMR analysis of the residue revealed incomplete conversion. The residue is dissolved again in cone. H2SO4 (40 mL) and the mixture is stirred for 4 h at room temperature. The mixture is poured in icy water and extracted with DCM. The organic layer is dried and concentrated. The residue is triturated with petroleum ether to yield the desired product.

Reference： [1]Patent: US2015/57260,2015,A1 .Location in patent: Paragraph 0553; 0554
[2]Patent: WO2015/25026,2015,A1 .Location in patent: Page/Page column 138
[3]Patent: WO2008/92942,2008,A2 .Location in patent: Page/Page column 22-23
[4]Patent: WO2006/53166,2006,A1 .Location in patent: Page/Page column 58-59
[5]Patent: WO2006/122137,2006,A1 .Location in patent: Page/Page column 72
[6]New Journal of Chemistry,2016,vol. 40,p. 9194 - 9204
[7]Patent: WO2017/12647,2017,A1 .Location in patent: Paragraph 0477
[8]Patent: WO2006/122137,2006,A1

4
[ 175461-33-3 ]
[ 914942-85-1 ]

Yield	Reaction Conditions	Operation in experiment
61%		Sulfuric acid (1.4 L) was cooled to 0 0C and A1.6 (70Og, 3.95 mol) was added portionwise over a period of 1.5h while maintaining the temperature between -5 0C and 0 0C. Fuming nitric acid (700 niL) was added over Ih while maintaining the reaction at 0 0C and the reaction was stirred at 0 0C for one hour and poured onto ice. The reaction mixture was extracted with dichloromethane (3 X 3L) and the solvent removed under reduced pressure to produce N-(2,6-dichloropyridin-4-yl)-N- methylnitramide (535g 61%)

Reference： [1]New Journal of Chemistry,2016,vol. 40,p. 9194 - 9204
[2]Patent: WO2006/122137,2006,A1 .Location in patent: Page/Page column 73

5
[ 175461-33-3 ]
[ 24424-99-5 ]
[ 1569084-56-5 ]

Yield	Reaction Conditions	Operation in experiment
90.3%	With triethylamine; In dichloromethane; at 20℃;	EXAMPLE 12-10Preparation of Compound 12-RR[0703j To a solution of 12-QQ (1.77 g, 10.0 mmol) in DCM (60 mL) was added Et3N (2.02 g, 20.0 mmol) and (Boc)20 (2.18 g, 10.0 mmol). The mixture was stirred at rt overnight. The mixture was neutralized with a saturated NaHCO3 solution. The organic layer was evaporated to give the crude product. The residue was purified by a silica gel column using PE/EA = 20/1 to 5/1 as elute to afford 12-RR as a white solid (2.5 g, 90.3 %). +ESI-MS: mlz 277.0 [M +H].

Reference： [1]Patent: WO2014/31784,2014,A1 .Location in patent: Paragraph 0703

6
[ 175461-33-3 ]
[ 914942-86-2 ]

Reference： [1]Patent: US2015/57260,2015,A1
[2]Patent: WO2015/25026,2015,A1
[3]New Journal of Chemistry,2016,vol. 40,p. 9194 - 9204
[4]Patent: WO2006/122137,2006,A1
[5]Patent: WO2006/122137,2006,A1

7
[ 175461-33-3 ]
[ 887147-19-5 ]

8
[ 175461-33-3 ]
(R)-3-((3-(6-chloro-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)ethynyl)-3-hydroxy-1-methylpyrrolidin-2-one [ No CAS ]

Reference： [1]Patent: US2015/57260,2015,A1
[2]Patent: WO2015/25026,2015,A1

9
[ 175461-33-3 ]
methyl 4-(3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-6-carboxylate [ No CAS ]

Reference： [1]Patent: US2015/57260,2015,A1
[2]Patent: WO2015/25026,2015,A1

10
[ 2402-78-0 ]
[ 175461-33-3 ]