[ CAS No. 10167-97-2 ] {[proInfo.proName]}

Name: 10167-97-2|2-Amino-5-methoxypyridine|95%
Brand: Ambeed
SKU: A468928
Rating: 97 (26 reviews)

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 10167-97-2

Structure of 10167-97-2 * 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 [ 10167-97-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 10167-97-2 ]

SDS Specification

Alternatived Products of [ 10167-97-2 ]

Product Details of [ 10167-97-2 ]

CAS No. :	10167-97-2	MDL No. :	MFCD07374873
Formula :	C₆H₈N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	XJKJHILCYUUVSJ-UHFFFAOYSA-N
M.W :	124.14	Pubchem ID :	11320934
Synonyms :

Calculated chemistry of [ 10167-97-2 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	35.13
TPSA :	48.14 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.72 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.64
Log Po/w (XLOGP3) :	0.48
Log Po/w (WLOGP) :	0.68
Log Po/w (MLOGP) :	-0.07
Log Po/w (SILICOS-IT) :	0.64
Consensus Log Po/w :	0.67

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.34
Solubility :	5.68 mg/ml ; 0.0458 mol/l
Class :	Very soluble
Log S (Ali) :	-1.06
Solubility :	10.8 mg/ml ; 0.087 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.75
Solubility :	2.21 mg/ml ; 0.0178 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.68

Safety of [ 10167-97-2 ]

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 [ 10167-97-2 ]

* 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 [ 10167-97-2 ]
Downstream synthetic route of [ 10167-97-2 ]

[ 10167-97-2 ] Synthesis Path-Upstream 1~19

1
[ 10167-97-2 ]
[ 55717-46-9 ]

Yield	Reaction Conditions	Operation in experiment
51.8%	at 90 - 93℃; for 24 h;	95 percent H₂SO₄ (10 mL) was stirred at 80 °C, compound 5 (5 mmol, 0.62 g) was added dropwise to the stirred solution keeping the temperature at 80-85 °C. After the addition, stirring was continued at 90-93 °C for about 24 h until 5 can not be detected by TLC. The reaction mixture was poured into crash ice (100 g) and the solution was adjusted to pH 7-8 by gradual addition of Na₂CO₃. The resulting mixture was extracted several times with diethyl ether (Scheme-I). The combined organic phases were dried with anhydrous Na₂SO₄ and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (gradient elution: CH₃OH/CH₂Cl₂ = 1:9) to give taupe solid 6 (0.29 g, yield = 51.8 percent). ¹H NMR (400 Hz, DMSO-d₆), δ (ppm): 5.200 (br, 2H, NH₂), 6.327-6.350 (t, 1H, pyr-H), 6.893-6.923 (dd, 1H, pyr-H), 7.497-7.506 (dd, 1H, pyr-H), 8.636 (s, 1H, OH). ¹³C NMR (100 MHz, DMSO-d₆), δ (ppm): 110.00, 128.16, 131.65, 145.25, 150.04.
44%	Stage #1: With hydrogen bromide In waterHeating / reflux Stage #2: With ammonia In methanol; dichloromethane	A solution of compound 119 in a 48percent aqueous HBr solution was refluxed overnight. The reaction mixture was concentrated under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (7M NH₃) 9:1) to give 6-amino-pyridin-3-ol (120) (6.9 g, yield = 44percent) as dark brown crystals. ¹H NMR (δ, DMSO-D6): 5.19 (2H, s), 6.33 (IH, d, J = 8.7 Hz), 6.90 (IH, dd, J = 8.7, 3.0 Hz), 7.50 (IH, d, J = 3.0 Hz), 8.61 (IH, s).

Reference： [1] Asian Journal of Chemistry, 2016, vol. 28, # 6, p. 1403 - 1404
[2] Patent: WO2007/113290, 2007, A1, . Location in patent: Page/Page column 40; 42

2
[ 638352-78-0 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydroxylamine hydrochloride; triethylamine In ethanol; water for 20 h; Heating / reflux	A mixture of 118 (1.0 equiv., 257 mmol, 52.0 g), hydroxylamine hydrochloride(6.5 equiv., 1671 mmol, 69.5 g), triethylamine (2.0 equiv., 514 mmol, 52.0 g), ethanol(400 ml) and water (200 ml) was refiuxed for 20 h. The solution was cooled and <n="43"/>quenched with 2 M HCl, washed with isopropyl ether and the pH was adjusted to 9-10 with 6 M NaOH. The resulting mixture was extracted several times with dichloro- methane. The combined organic phases were dried with MgSO₄ and the solvent was removed in vacuo. The oily residue was purified by column chromatography on silica gel (gradient elution: dichloromethane / ethyl acetate 25:75 -> ethyl acetate) to give 2-amino-5-methoxy-pyridine (119) (32.0 g, yield = 100 percent). ¹U NMR (δ, CDCl₃): 3.74 (3H, s), 4.45 (2H, s {br)\\ 6.45 (IH, d, J = 8.8 Hz), 7.07 (IH, dd, J = 8.8, 3.3 Hz), 7.72 (IH, d, J = 3.3 Hz)
100%	With hydroxylamine hydrochloride; triethylamine In ethanol; water for 20 h; Reflux	A mixture of 4 (7 mmol, 1.41 g), hydroxylamine hydrochloride (45.5 mmol, 1.89g), triethylamine (14 mmol, 1.41 g), ethanol (20 mL) and water (10 mL) was refluxed for 20 h. The solution was cooled and quenched with 2 M HCl, washed with isopropyl ether and the pH was adjusted to 9-10 with 6 M NaOH. The resulting mixture was extracted several times with diethyl ether. The combined organic phases were dried with MgSO₄ and the solvent was removed in vacuo. The oily residue was purified by column chromatography on silica gel (gradient elution: CH₂Cl₂/CH₃COOC₂H₅ = 1:3 → pure ethyl acetate) to give dark brown liquid 5 (0.87 g, yield = 100 percent). ¹H NMR (400 Hz, CDCl₃), δ (ppm): 3.772 (s, 3H, OCH₃), 4.213 (br, 2H, NH₂), 6.493-6.462 (dd, 1H, pyr-H), 7.070-7.110 (dd, 1H, pyr-H), 7.766-7.775 (d, 1H, pyr-H). ¹³C NMR (100 MHz, CDCl₃), δ (ppm): 56.28, 109.49, 125.73, 133.11, 148.60, 153.09.

Reference： [1] Patent: WO2007/113290, 2007, A1, . Location in patent: Page/Page column 40-42
[2] Asian Journal of Chemistry, 2016, vol. 28, # 6, p. 1403 - 1404
[3] European Journal of Organic Chemistry, 2003, # 20, p. 3948 - 3957

3
[ 76066-07-4 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With hydrazine In ethanol for 0.75 h; Heating / reflux	2-Ammo-5-methoxypyridineA mixtrure of 2-bromo-3-methoxy-6-nitropyridine (1.20 g, 5.15 mmol), hydrazine hydrate (6 mL), Pd on carbon (10 percent, 400 mg) in ethanol (40 mL) was heated at reflux for 45 min. The mixture was allowed to cool, filtered through Celite^.(R). and concentrated. Water (20 mL) and NH₃ (sat, aq.; 10 mL) were added and the mixture extracted with chloroform (2x50 mL). The combined organic extracts were dried (Na₂SO₄) and concentrated to give the title product as a low melting colourless solid. Yield: 615 mg (96percent).¹H NMR (DMSOd₆, 400 MHz) δ 7.64 (dd₅ IH), 7.10 (dd, IH)₅ 6.42 (dd, IH)₅ 5.43 (br. s, 2H), 3.68 (s, 3H).
96%	With hydrazine In ethanol; water for 0.75 h; Heating / reflux	A mixture of 2-bromo-3-methoxy-6-nitroρyridine (1.20 g, 5.15 mmol)₅ hydrazine hydrate (6 niL) and Pd-C (10 percent, 400 mg) in EtOH (40 mL) was heated at reflux for 45 min. The mixture was filtered through Celite^.(R). and concentrated in vacuo, Water (20 mL) and NH₃ (aq., sat.; 10 mL) were added and the mixture was extracted with CHCl₃ (2x50 mL). The combined extracts were dried (Na₂SO₄₎ and concentrated in vacuo to give the title product (615 mg, 96percent) as a low melting colourless solid. ¹R NMR (DMSO-d₆, 400 MHz) δ 7.64 (dd, IH)₅ 7.10 (dd, IH), 6.42 (dd, IH)₅ 5.43 (br. s, 2H)₅ 3.68 (s, 3H).
16 g	With palladium on activated charcoal; hydrogen; potassium acetate In methanol; ethyl acetate at 50℃; for 48 h;	To a solution of 2-bromo-3-methoxy-6-nitropyridine (33.0 g) in methanol (400 mL) and EA (100 mL) was added potassium acetate (15.3 g) and Pd/C (1.5 g). The mixture was stirredat 50°C for 48 hours under H2 (50 psi). The mixture was filtered. The filtrate was concentrated in vacuo to afford 5-methoxypyridin-2-amine (16.0 g).

Reference： [1] Patent: WO2007/51981, 2007, A1, . Location in patent: Page/Page column 57
[2] Patent: WO2007/51982, 2007, A1, . Location in patent: Page/Page column 49
[3] Pharmazie, 2000, vol. 55, # 12, p. 907 - 912
[4] Journal of Medicinal Chemistry, 2009, vol. 52, # 3, p. 637 - 645
[5] Australian Journal of Chemistry, 1981, vol. 34, # 4, p. 927 - 932
[6] Journal of Medicinal Chemistry, 1981, vol. 24, # 1, p. 39 - 42
[7] Patent: EP2022792, 2009, A1, . Location in patent: Page/Page column 10; 28
[8] Patent: EP2042501, 2009, A1, . Location in patent: Page/Page column 2; 8-9; 15; 24-25
[9] Patent: EP2098523, 2009, A1, . Location in patent: Page/Page column 10
[10] Patent: EP2213671, 2010, A1, . Location in patent: Page/Page column 9; 24
[11] Patent: EP2213672, 2010, A1, . Location in patent: Page/Page column 15; 27
[12] Patent: WO2015/181186, 2015, A1, . Location in patent: Page/Page column 131

4
[ 1072-97-5 ]
[ 124-41-4 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
36%	at 135℃; for 14 h;	5-methoxypyridin-2-amine (P5).; Method a: 2-Amino-4-bromopyridine (0.10 g; 0.58 mmol), sodium methoxide (0.16 g; 2.9 mmol) and copper powder nanosized activated (0.11 g; 1.74 mmol) were introduced in a screw cap vial (Pyrex glass) together with 2.0 mL of anhydrous MeOH and a stirrer bar. The vial was closed and put in an oil bath at 135°C and stirred for 14 h. The mixture was cooled, diluted with MeOH (5.0 mL) and filtered through an SPE silica gel cartridge and the product eluted with AcOEt. The fractions were <n="13"/>collected and evaporated obtaining a crude of 92 mg of product which was further purified by FCC (DCM/AcOEt = 1:1) to give 26 mg (yield 36percent) of the title compound as brown oil.; Attempts to improve the result were made by increasing the equivalents of catalyst used. It was believed that copper could be coordinated and thus inactivated by the nitrogen atoms of the substrate. By this means the expected product was achieved in 36percent yield (eq 3). The reaction mixture, after being heated for 14 hrs, still contained a significant amount of starting material together with black polymers. The reaction was quenched to avoid further formation of polymers and degradation of the formed product.
34.3%	at 100℃; for 48 h; Sealed tube	A mixture of 2-amino-5-bromopyridine (5.0 g, 28.9 mmol), sodium methoxide (6.3 g, 116.6 mmol) and copper powder (1.85 g, 28.9 mmol) in methanol (30 mL) was heated in sealed tube for 48 h at 100° C. The reaction mixture was cooled to room temperature, diluted with dichloromethane (50 mL), filtered through a pad of celite and the filtrate was concentrated under reduced pressure. The residue was diluted with water, extracted with dichloromethane (2.x.100 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL). The organic layer was dried over anhydrous Na₂SO₄and concentrated under vacuum. The crude material was purified over silica gel column chromatography eluting with EtOAc:Hexane (6:4) to afford Int-1 (1.2 g, 34.3percent) as brown color oil. To a solution of Int-1 (3.0 g, 24.2 mmol) in dimethoxy ethane (30 mL) was added 3-chloro-2,4-pentanedione (4.9 g, 36.4 mmol) at room temperature and the mixture was stirred at reflux temperature for 16 hours. The volatile was concentrated under reduced pressure. The residue was purified over silica gel column chromatography eluting with MeOH:DCM (1:9) to afford Int-2 (2.3 g, 46.6percent) as brown color oil. A solution of Int-2 (1.5 g, 7.35 mmol) in DMF DMA (15 mL) was stirred at reflux temperature for 24 hours. The reaction mixture was cooled to room temperature and diluted with diethyl ether (15 mL) and stirred for 15 minutes. The precipitated solid was filtered, washed with ether (2.x.10 mL) and dried under vacuum to afford Int-3 (1.2 g, 63percent) as brown solid. Mass (m/z): 260 [M⁺+1]. ¹H NMR (200 MHz, CDCl₃): δ 9.43 (d, J=2.2 Hz, 1H), 7.8 (d, J=12.4 Hz, 1H), 7.44 (d, J=9.8 Hz, 1H), 7.09 (dd, J=2.2, 9.6 Hz, 1H), 5.58 (d, J=12 Hz, 1H), 3.86 (s, 3H), 3.06 (brs, 6H), 2.75 (s, 3H). To a solution of Int-3 (1.6 g, 6.17 mmol) in DMF (25 mL) was added Int-3B (2.38 g, 12.3 mmol) followed by K₂CO₃(2.13 g, 15.4 mmol) at room temperature under inert atmosphere and the reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was cooled to room temperature, poured into ice water (70 mL) and stirred for 15 minutes. The precipitated solid was filtered, washed with water (2.x.10 mL) and dried under vacuum to afford Int-4 (1.2 g, 50percent) as brown solid. Mass (m/z): 390 [M⁺+1]. ¹H NMR (200 MHz, dmso-d₆): δ 10.13 (s, 1H), 9.17 (s, 1H), 8.59 (d, J=5.6 Hz, 1H), 8.-6.90 (m, 4H), 7.55 (d, J=10 Hz, 1H), 7.25-7.14 (m, 2H), 3.8 (s, 3H), 3.66 (s, 3H), 2.6 (s, 3H). A mixture of Int-4 (0.8 g, 2.05 mmol) and 4 N HCl (30 mL) was stirred at reflux temperature for 4 hours. The reaction mixture was cooled to room temperature and pH adjusted to about 5 using NaHCO₃and stirred for 20 minutes. The precipitated solid was filtered, washed with water (2.x.10 mL) and dried under vacuum to afford Int-5 (0.7 g, 90.9percent yield) as brown color solid. Mass (m/z): 376 [M⁺+1]. ¹H NMR (200 MHz, dmso-d₆): δ 10.29 (s, 1H), 9.18 (d, J=1.8 Hz, 1H), 8.72 (d, J=5.2 Hz, 1H), 8.-7.78 (m, 6H), 7.64 (dd, J=2.2, 10 Hz, 1H), 3.71 (s, 3H), 2.69 (s, 3H). To a stirred solution of Int-5 (0.7 g, 1.86 mmol) in DMF (10 mL) were added HOBt (0.25 g, 1.86 mmol), EDCI (0.71 g, 3.7 mmol), N-ethyldiisopropylamine (0.7 mL, 5.58 mmol) at 0° C. After being stirred for 10 minutes, and then added o-phenylenediamine (0.2 g, 1.86 mmol) to the reaction mixture at 0° C. The reaction mixture was warmed to room temperature and stirring was continued for 16 hours. The reaction mixture was poured into ice cold water (50 mL) and stirred for 10 minutes. The precipitated solid was filtered, washed with water (3.x.10 mL) and dried under vacuum. The crude material was purified over silica gel column chromatography eluting with 4percent MeOH/DCM to afford the title compound (0.27 g, 31.1percent yield) as off white solid. Mass (m/z): 465.2 [M⁺+1]. ¹H NMR (200 MHz, dmso-d₆): δ 10.02 (s, 1H), 9.53 (s, 1H), 9.18 (s, 1H), 8.59 (d, J=5.6 Hz, 1H), 7.86-7.98 (m, 4H), 7.60 (d, J=9.6 Hz, 1H), 7.13-7.25 (m, 3H), 6.85-7.0 (m, 1H), 6.75 (d, J=8.0 Hz, 1H), 6.45-6.61 (m, 1H), 4.86 (brs, 2H), 3.69 (s, 3H), 2.60 (s, 3H). ¹³C NMR (125 MHz, dmso-d₆): δ 164.69, 159.26, 158.17, 156.83, 148.74, 146.45, 143.33, 143.03, 142.42, 128.49, 127.05, 126.55, 126.21, 123.65, 120.66, 118.59, 118.10, 116.37, 116.29, 116.15, 110.27, 110.15, 55.90, 16.36.
17%	at 140℃; for 0.5 h; Microwave irradiation (75W) in a sealed tube	Method b:; 2-Amino-4-bromopyridine (0.10 g; 0.58 mmol), sodium methoxide (0.16 g; 2.9 mmol) and copper powder nanosized activated (0.11 g; 1.74 mmol) were introduced in a microwave glass tube with 1.5 mL of anhydrous DMF and sealed. The tube was introduced in the microwave cavity and heated for 30 min at 140°C (140C30M75W300Psi). Although DMF is a high boiling solvent, high pressure was observed, probably caused by the partial methanolysis of the DMF resulting in low boiling products such as methyl formate and dimethylamine. The mixture was diluted with 10 mL of 2 M NH₄Cl solution and extracted 3 times with AcOEt. The organic phase was washed 2 times with 2 M NH₄Cl solution and 1 time with water to remove the remaining DMF, dried on NaSO₄, and filtered. After the solvent was removed, the crude product was purified by FCC (AcOEt) to afford 12 mg (yield 17percent) of the title compound as brown oil. ¹H NMR (270 MHz; CDCl₃), δ 7.74 (1 H, d, ³J_HH = 3.0 Hz), 7.06 ( IH, dd, ³J_HH = 9.0 Hz, ⁴J_HH = 3.0 Hz), 6.45 (1 H, d, ³J_HH = 9.0 Hz), 3.95 (2H, bs, NH₂), 3.74 (3H, s, OCH₃); m/z (EI-MS): 124 (M⁺), 109 ([M-CH₃]⁺).; Substitution of halide by OCH₃ and SEt group is more challenging. The first attempts to prepare P5 by a nucleophilic aromatic displacement of the bromide with a methoxy group catalyzed by Cu powder in a conventional way¹¹ or with microwave heating or an ultrasound bath were frustrated by the apparent unreactivity of the substrate.; In order to decrease the reaction time, the transformation in eq 3 was carried out with microwave irradiation according to Table 3.

Reference： [1] Heterocycles, 2002, vol. 57, # 1, p. 55 - 71
[2] Journal of Medicinal Chemistry, 2007, vol. 50, # 19, p. 4746 - 4758
[3] Patent: WO2007/124345, 2007, A2, . Location in patent: Page/Page column 10; 25
[4] Patent: US2010/29638, 2010, A1, . Location in patent: Page/Page column 96
[5] Patent: WO2007/124345, 2007, A2, . Location in patent: Page/Page column 11; 24-25
[6] Patent: WO2003/76442, 2003, A1, . Location in patent: Page/Page column 83
[7] Patent: WO2007/124345, 2007, A2, . Location in patent: Page/Page column 25

5
[ 20511-12-0 ]
[ 124-41-4 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
31%	With copper In methanol at 160℃;	2-Amino-5-methoxy-pyridine. A mixture OF 2-AMINO-5-IODO-PYRIDINE (1 g, 4.54 mmol) in 20 mL of absolute methanol with 400 mg of copper powder and sodium methoxide (6 mmol) was heated at 160 °C overnight in a seal tube. The reaction mixture was cooled to room temperature, diluted with 80 mL of methanol and filtered through a pad of celite. The filtrate was concentrated and the residue was purified by chromatography (80percent ethyl acetate/hexane) to give the title compound (174 mg, 31percent). 1H NMR (CDCl3) : 7.78 (d, J = 2.7, 1H), 7.09 (dd, J = 3.0, 9.0, 1H), 6.48 (d, J= 9.0, 1H), 3.78 (s, 3H).

Reference： [1] Patent: WO2005/3100, 2005, A2, . Location in patent: Page 231

6
[ 76066-07-4 ]
[ 10167-97-2 ]

Reference： [1] Patent: EP2216051, 2010, A1,
[2] Patent: EP2216052, 2010, A1,

7
[ 24100-18-3 ]
[ 10167-97-2 ]

Reference： [1] Pharmazie, 2000, vol. 55, # 12, p. 907 - 912
[2] Australian Journal of Chemistry, 1981, vol. 34, # 4, p. 927 - 932
[3] Journal of Medicinal Chemistry, 1981, vol. 24, # 1, p. 39 - 42
[4] Patent: WO2015/181186, 2015, A1,

8
[ 105170-27-2 ]
[ 10167-97-2 ]

Reference： [1] Organometallics, 2018, vol. 37, # 18, p. 2941 - 2944
[2] Advanced Synthesis and Catalysis, 2013, vol. 355, # 4, p. 627 - 631

9
[ 20511-12-0 ]
[ 12775-96-1 ]
[ 10167-97-2 ]

Reference： [1] Patent: US3984549, 1976, A,

10
[ 20511-12-0 ]
[ 67-56-1 ]
[ 10167-97-2 ]

Reference： [1] Journal of Medicinal Chemistry, 1997, vol. 40, # 19, p. 3109 - 3118
[2] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 16, p. 4790 - 4793

11
[ 477889-91-1 ]
[ 10167-97-2 ]

Reference： [1] European Journal of Organic Chemistry, 2003, # 20, p. 3948 - 3957

12
[ 6602-32-0 ]
[ 10167-97-2 ]

Reference： [1] Patent: WO2015/181186, 2015, A1,

13
[ 228710-82-5 ]
[ 10167-97-2 ]

Reference： [1] Asian Journal of Chemistry, 2016, vol. 28, # 6, p. 1403 - 1404

14
[ 10167-97-2 ]
[ 105170-27-2 ]

Yield	Reaction Conditions	Operation in experiment
63%	With sodium hydroxide; bromine; sodium nitrite In water; hydrogen bromide	(a) 2-Amino-5-methoxypyridine (14.8 g, prepared by the method of J.G. Lombardino, J. Med. Chem., 1981, 24, 39) was dissolved in 60percent hydrobromic acid (150 ml) and to the cooled (-10°) stirred solution bromine (47.47 g) was added dropwise. To the resulting yellow suspension was added, dropwise, sodium nitrite (20.53 g) in water (40 ml), keeping the temperature below -5°. The mixture was stirred to room temperature, and after 0.5 hour cooled to 0°, and a solution of sodium hydroxide (120 g) in water (100 ml) was slowly added. The mixture was thoroughly extracted with ether, the combined ether extracts dried with anhydrous sodium sulphate, and evaporated. The residue was chromatographed on silica gel (150 g). Elution with dichloromethane gave a yellow oil (14.1 g, 63percent) which was combined with a smaller batch (3.4 g) and distilled under reduced pressure to give 2-bromo-5-methoxypyridine (16.4 g). b.p. 76°-78°/0.6 torr.
63%	With sodium hydroxide; bromine; sodium nitrite In water; hydrogen bromide	(a) 2-Amino-5-methoxypyridine (14.8 g, prepared by the method of J.G. Lombardino, J. Med. Chem. , 1981, 24 , 39) was dissolved in 60percent hydrobromic acid (150 ml) and to the cooled (-10°) stirred solution bromine (47.47 g) was added dropwise. To the resulting yellow suspension was added, dropwise, sodium nitrite (20.53 g) in water (40 ml), keeping the temperature below -5°. The mixture was stirred to room temperature, and after 0.5 hour cooled to 0°, and a solution of sodium hydroxide (120 g) in water (100 ml) was slowly added. The mixture was thoroughly extracted with ether, the combined ether extracts dried with anhydrous sodium sulphate, and evaporated. The residue was chromatographed on silica gel (150 g). Elution with dichloromethane gave a yellow oil (14.1 g, 63percent) which was combined with a smaller batch (3.4 g) and distilled under reduced pressure to give 2-bromo-5-methoxypyridine (16.4 g). b.p. 76-78°/0.6 torr.

Reference： [1] Pharmazie, 2000, vol. 55, # 12, p. 907 - 912
[2] Patent: US4766121, 1988, A,
[3] Patent: EP188351, 1991, B1,
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 3085 - 3096

15
[ 10167-97-2 ]
[ 22187-96-8 ]

Reference： [1] Pharmazie, 2000, vol. 55, # 12, p. 907 - 912

16
[ 10167-97-2 ]
[ 139585-48-1 ]

Reference： [1] European Journal of Organic Chemistry, 2003, # 20, p. 3948 - 3957

17
[ 10167-97-2 ]
[ 1092394-16-5 ]

Reference： [1] Patent: WO2009/136663, 2009, A1,

18
[ 107-20-0 ]
[ 10167-97-2 ]
[ 955376-51-9 ]

Yield	Reaction Conditions	Operation in experiment
15 g	With sodium hydrogencarbonate In methanol; water for 2 h; Reflux	To a solution of 5-methoxypyridin-2-amine (15.0 g) in methanol (40 mL) and water (20 mL) was added 2-chloroacetaldehyde (25.0 g) and sodium bicarbonate (10.2 g). The mixture was stirred under reflux for 2 hours, and then concentrated. The residue was partionedbetween EA and aq. NaH CO3 solution. The organic layer was concentrated and purified by column chromatography to afford 6-methoxyimidazo[1 ,2-a]pyridine (15.0 g).

Reference： [1] Journal of Medicinal Chemistry, 2009, vol. 52, # 3, p. 637 - 645
[2] Patent: WO2015/181186, 2015, A1, . Location in patent: Page/Page column 131

19
[ 10167-97-2 ]
[ 1100750-16-0 ]

Reference： [1] Patent: WO2015/181186, 2015, A1,

[ 10167-97-2 ] Synthesis Path-Downstream 1~88

1
[ 40288-65-1 ]
[ 10167-97-2 ]
[ 142073-99-2 ]

Reference： [1]Australian Journal of Chemistry,1992,vol. 45,p. 877 - 888

2
[ 1075-47-4 ]
[ 10167-97-2 ]
6-Methoxy-2-p-tolyl-imidazo[1,2-a]pyridin-3-ol [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1992,vol. 45,p. 877 - 888

3
[ 10167-97-2 ]
[ 92895-33-5 ]
[ 136117-56-1 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1991,vol. 39,p. 1556 - 1567

4
[ 10167-97-2 ]
[ 619-41-0 ]
[ 142073-96-9 ]

Reference： [1]Australian Journal of Chemistry,1992,vol. 45,p. 877 - 888

5
[ 10167-97-2 ]
[ 99-73-0 ]
[ 118000-69-4 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 105℃; for 3.5h;	844 mg (corresponding to 3.0 mmol) of 2-bromo-4'-bromoacetophenone and 378 mg (corresponding to 3.0 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 25 mL of acetonitrile. The resulting solution was heated under reflux in an oil bath at 105°C for 3.5 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The filtered precipitates were washed with acetonitrile and dried under reduced pressure to obtain crude crystals. The resulting crude crystals were suspended in a mixed solution of 7 mL of water and 7 mL of methanol. Then, about 7 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using an ultrasonic washing machine. Precipitates were filtered, sufficiently Mashed with Mater, and dried under reduced pressure, to obtain 640 mg (corresponding to 2.11 mmol) of 2-(4'-bromophenyl)-6-methoxyimidazo[1,2-a]pyridine (Fig. 1, step 4).

Reference： [1]Journal of Heterocyclic Chemistry,1988,vol. 25,p. 129 - 137
[2]Patent: EP2098523,2009,A1 .Location in patent: Page/Page column 10

6
[ 76066-07-4 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With hydrazine;palladium 10% on activated carbon; In ethanol; for 0.75h;Heating / reflux;	2-Ammo-5-methoxypyridineA mixtrure of 2-bromo-3-methoxy-6-nitropyridine (1.20 g, 5.15 mmol), hydrazine hydrate (6 mL), Pd on carbon (10 percent, 400 mg) in ethanol (40 mL) was heated at reflux for 45 min. The mixture was allowed to cool, filtered through Celite.(R). and concentrated. Water (20 mL) and NH3 (sat, aq.; 10 mL) were added and the mixture extracted with chloroform (2x50 mL). The combined organic extracts were dried (Na2SO4) and concentrated to give the title product as a low melting colourless solid. Yield: 615 mg (96percent).1H NMR (DMSOd6, 400 MHz) delta 7.64 (dd5 IH), 7.10 (dd, IH)5 6.42 (dd, IH)5 5.43 (br. s, 2H), 3.68 (s, 3H).
96%	With hydrazine;palladium 10% on activated carbon; In ethanol; water; for 0.75h;Heating / reflux;	A mixture of 2-bromo-3-methoxy-6-nitrorhoyridine (1.20 g, 5.15 mmol)5 hydrazine hydrate (6 niL) and Pd-C (10 percent, 400 mg) in EtOH (40 mL) was heated at reflux for 45 min. The mixture was filtered through Celite.(R). and concentrated in vacuo, Water (20 mL) and NH3 (aq., sat.; 10 mL) were added and the mixture was extracted with CHCl3 (2x50 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the title product (615 mg, 96percent) as a low melting colourless solid. 1R NMR (DMSO-d6, 400 MHz) delta 7.64 (dd, IH)5 7.10 (dd, IH), 6.42 (dd, IH)5 5.43 (br. s, 2H)5 3.68 (s, 3H).
	With hydrazine;palladium 10% on activated carbon; In ethanol; water; for 0.75h;Heating / reflux;	17.36 g (corresponding to 74.50 mmol) of 2-bromo-3-methoxy-6-nitropyridine was dissolved in 520 mL of ethanol, and 11.63 g (50percent wet) of 10 percent palladium-carbon was added thereto under argon atmosphere. To the mixture, 88.4 mL of hydrazine monohydrate was added dropwise. After the reaction mixture was refluxed for 45 minutes, the reaction solution was cooled down to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washings were combined with the filtrate. The combined solution was concentrated under reduced pressure. Then, 402 mL of water and 38 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 8.14 g (corresponding to 65.57 mmol) of 2-amino-5-methoxypyridine (Fig. 5, Step 3).

	With hydrazine;palladium 10% on activated carbon; In ethanol; for 0.75 - 1.16667h;Heating / reflux;Product distribution / selectivity;	, Step 2). 55.6 g (corresponding to 0.239 mol) of 2-bromo-3-methoxy-6-nitropyridine was dissolved in 1700 mL of ethanol, and 37.3 g (50percent wet) of 10 percent palladium-carbon was added thereto under argon stream. To the mixture, 283 mL of hydrazine monohydrate was then added dropwise. After the reaction mixture was refluxed for 70 minutes, the reaction solution was cooled down to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washings were combined with the filtrate. The combined solution was concentrated under reduced pressure. Then, 1300 mL of water and 130 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 26.2 g (corresponding to 0.211 mol) of 2-amino-5-methoxypyridine ( 17.36 g (corresponding to 74.50 mmol) of 2-bromo-3-methoxy-6-nitropyridine was dissolved in 520 mL of ethanol, and 11.63 g (50percent wet) of 10 percent palladium-carbon was added thereto under argon stream. To the mixture, 88.4 mL of hydrazine monohydrate was added dropwise. After the reaction mixture was refluxed for 45 minutes, the reaction solution was cooled down to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washings were combined with the filtrate. The combined solutions was concentrated under reduced pressure. Then, 402 mL of water and 38 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 8.14 g (corresponding to 65.57 mmol) of 2-amino-5-methoxypyridine (Fig. 3, Step 3).; 55.6 g (corresponding to 0.239 mol) of 2-bromo-3-methoxy-6-nitropyridine was dissolved in 1700 mL of ethanol, and 37.3 g (50percent wet) of 10percent palladium-carbon was added thereto under argon stream. Then, 283 mL of hydrazine monohydrate was added dropwise. After the reaction mixture was refluxed for 70 minutes, the reaction solution was cooled down to room temperature. Then, palladium-carbon was filtered off, which was then washed with ethanol. The washings were combined with the filtrate. After the resulting solution was concentrated under reduced pressure, the concentrate was supplemented with 1300 mL of water and 130 mL of conc. aqueous ammonia, and extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure, to obtain 26.2 g (corresponding to 0.211 mol) of 2-amino-5-methoxypyridine (Fig. 1, Step 3).
	With hydrogen; hydrazine;palladium 10% on activated carbon; In ethanol; water; for 1.16667h;Reflux;	55.6 g (corresponding to 0.239 mol) of was dissolved in 1700 mL of ethanol, and 37.3 g (50percent. wet) of 10 percent palladium-carbon was added thereto under argon stream. To the mixture, 283 mL of hydrazine monohydrate was then added dropwise. After the reaction mixture was heated under reflux for 70 minutes, the reaction solution was cooled down to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washings were combined with the filtrate. The combined solution was concentrated under reduced pressure. Then, 1300 mL of water and 130 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 26.2 g (corresponding to 0.211 mol) of 2-amino-5-methoxypyridine (Fig. 1, Step 3).
	With hydrazine hydrate;palladium 10% on activated carbon; In ethanol; water; for 1.16667h;Reflux; Inert atmosphere;	55.6 g (corresponding to 0.239 mol) of 2-bromo-3-methoxy-6-nitropyridine was dissolved in 1700 mL of ethanol, and 37.3 g (50percent wet) of 10 percent palladium-carbon was added thereto under argon stream. To the mixture, 283 mL of hydrazine monohydrate was then added dropwise. After the reaction mixture was heated under reflux for 70 minutes, the reaction solution was cooled down to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washings were combined with the filtrate. The combined solution was concentrated under reduced pressure. Then, 1300 mL of water and 130 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 26.2 g (corresponding to 0.211 mol) of 2-amino-5-methoxypyridine (Fig. 3, Step 3).
	With hydrazine hydrate;palladium 10% on activated carbon; In ethanol; water; for 1.16667h;Inert atmosphere; Reflux;	55.6 g (corresponding to 0.239 mol) of 2-bromo-3-methoxy-6-nitropyridine was dissolved in 1700 mL of ethanol, and 37.3 g (50percent wet) of 10 palladium-carbon was added thereto under argon stream. To the mixture, 283 mL of hydrazine monohydrate was then added dropwise. After the reaction mixture was heated under reflux for 70 minutes, the reaction solution was cooled down to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washings were combined with the filtrate. The combined solution was concentrated under reduced pressure. Then, 1300 mL of water and 130 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 26.2 g (corresponding to 0.211 mol) of 2-amino-5-methoxypyridine (Fig. 9, Step 3).
16 g	With palladium on activated charcoal; hydrogen; potassium acetate; In methanol; ethyl acetate; at 50℃; under 2585.81 Torr; for 48h;	To a solution of 2-bromo-3-methoxy-6-nitropyridine (33.0 g) in methanol (400 mL) and EA (100 mL) was added potassium acetate (15.3 g) and Pd/C (1.5 g). The mixture was stirredat 50°C for 48 hours under H2 (50 psi). The mixture was filtered. The filtrate was concentrated in vacuo to afford 5-methoxypyridin-2-amine (16.0 g).

Reference： [1]Patent: WO2007/51981,2007,A1 .Location in patent: Page/Page column 57
[2]Patent: WO2007/51982,2007,A1 .Location in patent: Page/Page column 49
[3]Pharmazie,2000,vol. 55,p. 907 - 912
[4]Journal of Medicinal Chemistry,2009,vol. 52,p. 637 - 645
[5]Australian Journal of Chemistry,1981,vol. 34,p. 927 - 932
[6]Journal of Medicinal Chemistry,1981,vol. 24,p. 39 - 42
[7]Patent: EP2022792,2009,A1 .Location in patent: Page/Page column 10; 28
[8]Patent: EP2042501,2009,A1 .Location in patent: Page/Page column 2; 8-9; 15; 24-25
[9]Patent: EP2098523,2009,A1 .Location in patent: Page/Page column 10
[10]Patent: EP2213671,2010,A1 .Location in patent: Page/Page column 9; 24
[11]Patent: EP2213672,2010,A1 .Location in patent: Page/Page column 15; 27
[12]Patent: WO2015/181186,2015,A1 .Location in patent: Page/Page column 131

7
[ 63920-75-2 ]
[ 10167-97-2 ]
2-amino-4,6-dimethoxy-<i>N</i>-(5-methoxy-pyridin-2-yl)-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 2440 - 2455

8
[ 62266-36-8 ]
[ 10167-97-2 ]
2-methylene-cyclopropanecarboxylic acid (5-methoxy-pyridin-2-yl)-amide [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 5521 - 5524

9
[ 10167-97-2 ]
[ 55717-46-9 ]

Yield	Reaction Conditions	Operation in experiment
51.8%	With sulfuric acid; at 90 - 93℃; for 24h;	95 percent H2SO4 (10 mL) was stirred at 80 °C, compound 5 (5 mmol, 0.62 g) was added dropwise to the stirred solution keeping the temperature at 80-85 °C. After the addition, stirring was continued at 90-93 °C for about 24 h until 5 can not be detected by TLC. The reaction mixture was poured into crash ice (100 g) and the solution was adjusted to pH 7-8 by gradual addition of Na2CO3. The resulting mixture was extracted several times with diethyl ether (Scheme-I). The combined organic phases were dried with anhydrous Na2SO4 and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (gradient elution: CH3OH/CH2Cl2 = 1:9) to give taupe solid 6 (0.29 g, yield = 51.8 percent). 1H NMR (400 Hz, DMSO-d6), delta (ppm): 5.200 (br, 2H, NH2), 6.327-6.350 (t, 1H, pyr-H), 6.893-6.923 (dd, 1H, pyr-H), 7.497-7.506 (dd, 1H, pyr-H), 8.636 (s, 1H, OH). 13C NMR (100 MHz, DMSO-d6), delta (ppm): 110.00, 128.16, 131.65, 145.25, 150.04.
44%		A solution of compound 119 in a 48percent aqueous HBr solution was refluxed overnight. The reaction mixture was concentrated under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (7M NH3) 9:1) to give 6-amino-pyridin-3-ol (120) (6.9 g, yield = 44percent) as dark brown crystals. 1H NMR (delta, DMSO-D6): 5.19 (2H, s), 6.33 (IH, d, J = 8.7 Hz), 6.90 (IH, dd, J = 8.7, 3.0 Hz), 7.50 (IH, d, J = 3.0 Hz), 8.61 (IH, s).

Reference： [1]Asian Journal of Chemistry,2016,vol. 28,p. 1403 - 1404
[2]Patent: WO2007/113290,2007,A1 .Location in patent: Page/Page column 40; 42

10
[ 10167-97-2 ]
5-methoxy-5'-methyl-2,2'-bipyridine [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2003,p. 3948 - 3957

11
[ 477889-91-1 ]
[ 10167-97-2 ]

Reference： [1]European Journal of Organic Chemistry,2003,p. 3948 - 3957

12
[ 10167-97-2 ]
[ 431942-24-4 ]

Reference： [1]Heterocycles,2002,vol. 57,p. 55 - 71

13
[ 10167-97-2 ]
[ 431942-28-8 ]

Reference： [1]Heterocycles,2002,vol. 57,p. 55 - 71

14
[ 10167-97-2 ]
[ 431942-33-5 ]

Reference： [1]Heterocycles,2002,vol. 57,p. 55 - 71

15
[ 10167-97-2 ]
[ 431942-32-4 ]

Reference： [1]Heterocycles,2002,vol. 57,p. 55 - 71

16
[ 10167-97-2 ]
3-bromomethyl-5-methoxy-2-phenyl-furo[2,3-<i>b</i>]pyridine [ No CAS ]

Reference： [1]Heterocycles,2002,vol. 57,p. 55 - 71

17
[ 10167-97-2 ]
[ 431942-34-6 ]

Reference： [1]Heterocycles,2002,vol. 57,p. 55 - 71

18
[ 10167-97-2 ]
N-[2-(5-methoxy-2-phenylfuro[2,3-b]pyridin-3-yl)ethyl]acetamide [ No CAS ]

Reference： [1]Heterocycles,2002,vol. 57,p. 55 - 71

19
[ 24100-18-3 ]
[ 10167-97-2 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912
[2]Australian Journal of Chemistry,1981,vol. 34,p. 927 - 932
[3]Journal of Medicinal Chemistry,1981,vol. 24,p. 39 - 42
[4]Patent: WO2015/181186,2015,A1

20
[ 10167-97-2 ]
[ 325796-80-3 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

21
[ 10167-97-2 ]
[ 325796-82-5 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912
[2]Pharmazie,2000,vol. 55,p. 907 - 912

22
[ 10167-97-2 ]
5-Methoxy-2-(1-methoxycarbonyl-2,3-dihydro-1H-indol-3-ylmethyl)-1-methylpyridiniumiodid [ No CAS ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912
[2]Pharmazie,2000,vol. 55,p. 907 - 912

23
[ 10167-97-2 ]
[ 325796-84-7 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

24
[ 10167-97-2 ]
[ 325796-81-4 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912
[2]Pharmazie,2000,vol. 55,p. 907 - 912

25
[ 10167-97-2 ]
3-(5-Methoxypyridin-2-ylmethyl)-1H-indol [ No CAS ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

26
[ 10167-97-2 ]
[ 325796-74-5 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

27
[ 10167-97-2 ]
[ 325796-73-4 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

28
[ 10167-97-2 ]
[ 325796-77-8 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

29
[ 10167-97-2 ]
3-[1-Hydroxy-1-(5-methoxypyridin-2-yl)-methyl]-indol-1-carbonsaeuremethylester [ No CAS ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

30
[ 10167-97-2 ]
[ 325796-76-7 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

31
[ 10167-97-2 ]
[ 325796-79-0 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912
[2]Pharmazie,2000,vol. 55,p. 907 - 912

32
[ 10167-97-2 ]
[ 325796-72-3 ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

33
[ 10167-97-2 ]
C₂₃H₂₄BN₃O [ No CAS ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

34
[ 10167-97-2 ]
Bis-(1-benzylindol-3-yl)-5-methoxypyridin-2-yl-methan [ No CAS ]

Reference： [1]Pharmazie,2000,vol. 55,p. 907 - 912

35
[ 10167-97-2 ]
[ 196959-51-0 ]

Reference： [1]Australian Journal of Chemistry,1997,vol. 50,p. 719 - 725

36
[ 10167-97-2 ]
Acetoxy-[2-(4-chloro-phenyl)-6-methoxy-imidazo[1,2-a]pyridin-3-yl]-acetic acid ethyl ester [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1997,vol. 50,p. 719 - 725

37
[ 10167-97-2 ]
Acetylamino-[2-(4-chloro-phenyl)-6-methoxy-imidazo[1,2-a]pyridin-3-yl]-acetic acid ethyl ester [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1997,vol. 50,p. 719 - 725

38
[ 10167-97-2 ]
Benzoylamino-[2-(4-chloro-phenyl)-6-methoxy-imidazo[1,2-a]pyridin-3-yl]-acetic acid ethyl ester [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1997,vol. 50,p. 719 - 725

39
[ 10167-97-2 ]
[ 117296-85-2 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 596 - 604

40
[ 10167-97-2 ]
2-[(2-dimethylamino)benzylsulfinyl]-1-(5-methoxy-2-pyridyl)imidazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 596 - 604

41
[ 10167-97-2 ]
[ 117392-85-5 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 596 - 604

42
[ 10167-97-2 ]
{2-[1-(5-Methoxy-pyridin-2-yl)-1H-imidazole-2-sulfonylmethyl]-phenyl}-dimethyl-amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 596 - 604

43
[ 10167-97-2 ]
[ 142073-98-1 ]

Reference： [1]Australian Journal of Chemistry,1992,vol. 45,p. 877 - 888

44
[ 10167-97-2 ]
[ 142073-97-0 ]

Reference： [1]Australian Journal of Chemistry,1992,vol. 45,p. 877 - 888

45
[ 10167-97-2 ]
[ 142074-00-8 ]

Reference： [1]Australian Journal of Chemistry,1992,vol. 45,p. 877 - 888

46
[ 10167-97-2 ]
[ 77459-78-0 ]

Reference： [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 39 - 42

47
[ 10167-97-2 ]
[ 118000-71-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1988,vol. 25,p. 129 - 137

48
[ 10167-97-2 ]
[ 118000-70-7 ]

Reference： [1]Journal of Heterocyclic Chemistry,1988,vol. 25,p. 129 - 137

49
[ 10167-97-2 ]
[ 105190-21-4 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1988,p. 3085 - 3096

50
[ 20511-12-0 ]
[ 124-41-4 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
31%	With copper; In methanol; at 160℃;	2-Amino-5-methoxy-pyridine. A mixture OF 2-AMINO-5-IODO-PYRIDINE (1 g, 4.54 mmol) in 20 mL of absolute methanol with 400 mg of copper powder and sodium methoxide (6 mmol) was heated at 160 °C overnight in a seal tube. The reaction mixture was cooled to room temperature, diluted with 80 mL of methanol and filtered through a pad of celite. The filtrate was concentrated and the residue was purified by chromatography (80percent ethyl acetate/hexane) to give the title compound (174 mg, 31percent). 1H NMR (CDCl3) : 7.78 (d, J = 2.7, 1H), 7.09 (dd, J = 3.0, 9.0, 1H), 6.48 (d, J= 9.0, 1H), 3.78 (s, 3H).

Reference： [1]Patent: WO2005/3100,2005,A2 .Location in patent: Page 231

51
C₁₃H₁₄N₆ [ No CAS ]
[ 10167-97-2 ]
(5-methoxy-pyridin-2-yl)-[6-(4-methyl-pyrazol-1-yl)-pyridin-2-yl]-amine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In 1,4-dioxane; at 100℃;	To a solution of 1.66 mmol of 11 in 10 mL of anhydrous 1,4-dioxane was added 6.6 mmol of NaH (60percent in mineral oil) followed by the addition of 1.66 mmol of 21, and the resulting mixture was stirred at 100 °C overnight under N2. After the reaction was quenched with methanol, the solvents were removed. The residue was dissolved in 40 mL of ethyl acetate and the organic solution was washed with saturated NaCI, dried over MgS04, and concentrated under reduced pressure. The crude product was purified by column chromatography to give 0.8 mmol of 22. 1H NMR (300 MHz, DMSO-d6) 8 11.61 (s, 1H), 8.40 (s, 1H), 8.12 (d, J = 3.0 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.89 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 7.77 (dd, J1 = 5.7 Hz, J2 = 3.5 Hz, 1H), 7.65 (s, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 3.86 (s, 3H), 2.14 (s, 3H) ; MS m/z: 282 (M + 1).

Reference： [1]Patent: WO2005/100349,2005,A2 .Location in patent: Page/Page column 78

52
[ 517-23-7 ]
[ 10167-97-2 ]
[ 108-88-3 ]
3-(2-chloroethyl)-7-methoxy-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10 parts (30.4%)	With ammonium hydroxide; trichlorophosphate; In hexane; ethyl acetate;	a) A mixture of 17 parts of 5-methoxy-2-pyridinamine, 61 parts of phosphoryl chloride and 348 parts of methylbenzene was stirred for 2 hours at 60° C. 18 Parts of 3-acetyl-4,5-dihydro-2(3H)-furanone were added and the reaction mixture was stirred overnight at 90° C. The whole was poured into crushed ice and treated with ammonium hydroxide. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was stirred in a mixture of hexane and ethyl acetate (50:50 by volume). The precipitated product was filtered off and dried, yielding 10 parts (30.4percent) of 3-(2-chloroethyl)-7-methoxy-2-methyl-4H-pyrido-[1,2-a]pyrimidin-4-one; mp. 150° C. (intermediate 3)

Reference： [1]Patent: US5158952,1992,A

53
[ 20511-12-0 ]
[ 12775-96-1 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate; In methanol;	A. 2-Amino-5-methoxypyridine is prepared by combining 55 g. of 2-amino-5-iodopyridine, 20 g. of sodium methoxide, 5 g. of copper powder, 500 ml. of methanol in a glass lined bomb and rocking at 150° C. for 12 hours. Upon concentration to dryness, an extraction with chloroform extracts are dried and evaporated to dryness in vacuo. The residue is chromatographed on 1200 g. of silica gel eluding with 50percent ethylacetate and methylenechloride affording 2-amino-5-methoxy pyridine.

Reference： [1]Patent: US3984549,1976,A

54
[ 10167-97-2 ]
[ 7143-01-3 ]
N-(5-methoxy-2-pyridinyl)methanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	In dichloromethane; at 0 - 20℃; for 6h;	Preparation I; N-(5-methoxy-2-pyridinyl)methanesulfonamide; A solution of 10.7 g (86 mmol) of 5-methoxy-2-pyridinamine in 55 ml of dichioromethane is cooled to 0 C. and 72 ml (144 mmol) of a 2 M solution of methanesulfonic anhydride in dichloromethane are added gradually. The reaction mixture is stirred for 6 hours at room temperature and sodium bicarbonate solution is then added in a sufficient amount to bring the pH to about 9. The mixture obtained is concentrated under reduced pressure, the residue is taken up in 160 ml of ethanol at 50 C., the mixture obtained is dried and filtered and the filtrate is concentrated under reduced pressure. The residue is triturated in 50 ml of cold ethanol and the solid obtained is filtered off, rinsed with a little ethanol on the filter and then dried to give 8.7 g of the expected product in the form of a white powder (yield=50%).

Reference： [1]Patent: US2007/54955,2007,A1 .Location in patent: Page/Page column 4

55
C₁₁H₁₃NO₂ [ No CAS ]
[ 10167-97-2 ]
[ 925894-90-2 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 2.75 g (14.2 mmol) CM in 100 mL CH2CI2 was added 7.54 g (17.8 mmol) Dess-Martin Periodinane and the resultant mixture was stirred at room temperature 1 h. The reaction was quenched with a 5percent aqueous solution of Nua2Spsi3, followed by saturated aqueous NaHCO3-The biphasic mixture was stirred vigorously for 1 h, the layers were separated, the organic was washed with NaHCO3, water, dried over Na2SO4, and concentrated by rotary evaporation to provide the intermediate aldehyde as a white solid. This material was dissolved in 50 mL MeOH and 10 mL of CH2CI2, and 2.65 g (21.3 mmol) of <strong>[10167-97-2]5-methoxy-2-aminopyridine</strong> and 3 mL HOAc were added. After stirring 2 h at room temperature, 2.23 g (35.6 mmol) of NaCNBH3 was added and the reaction was allowed to stir overnight, after which the solvents were removed by rotary evaporation. The residue was EPO <DP n="39"/>dissolved in EtOAc, washed twice with 5percent aqueous NaHCpsi3, brine, dried over Na2SO4 and concentrated by rotary evaporation. The residue was purified twice by flash chromatography (SiC>2; CH2Cl2/MeOH, then EtOAc/hexanes) to provide Q2 as a black oil. Data for C1^: LC/MS: rt = 1.21 min; m/z (M+H) 300.0, found; 300.2 required.

Reference： [1]Patent: WO2007/19234,2007,A2 .Location in patent: Page/Page column 37-38

56
[ 10167-97-2 ]
[ 105-36-2 ]
BrH*C₁₀H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃; for 8h;	5-Methoxypyridin-2-amine (1.0 g, 8.04 mmol) (Lombardino, J. G. J. Med. Chem. 1981, 24, 39-42) was added to ethyl bromoacetate (5.4 mL, 48.2 mmol) and the reaction mixture was stirred at room temperature for 8 h. The precipitate was removed by filtration and washed with dry Et2O. The obtained HBr salt was treated with POBr3 (23.0 g, 80.4 mmol) and the mixture was heated at reflux, under a CaSO4 drying tube, for 2 h. Ice water was added and the solution was made basic by addition of NH4OH. The solution was extracted with CHCl3 and the organic phase was dried (MgSO4) and concentrated. The residue waso subjected to flash chromatography (Heptane/EtOAc gradient) to afford the title compound as a white solid (0.84 g). 1H NMR delta ppm 8.21 (d, IH) 7.96 (s, IH) 7.45 (d, IH) 7.09 (dd, IH) 3.78 (s, 3H); MS m/z (M+H) 227, 229.

Reference： [1]Patent: WO2008/91195,2008,A1 .Location in patent: Page/Page column 48-49

57
conc. aqueous ammonia [ No CAS ]
[ 76066-07-4 ]
[ 10167-97-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate;palladium-carbon; In ethanol; water;	, Step 2). 17.36 g (corresponding to 74.50 mmol) of 2-bromo-3-methoxy-6--nitropyridine was dissolved in 520 mL of ethanol, and 11.63 g (50percent wet) of 10 percent palladium-carbon was added thereto under argon stream. To the mixture, 88.4 mL of hydrazine monohydrate was added dropwise. After the reaction mixture was refluxed for 45 minutes, the reaction solution was cooled down to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washing were combined with the filtrate. The combined solution was concentrated under reduced pressure. Then, 402 mL of water and 38 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 8.14 g (corresponding to 65.57 mmol) of 2-amino-5-methoxypyridine (
	With hydrazine hydrate;palladium-carbon; In ethanol; water;	, Step 2). 55.6 g (corresponding to 0.239 mol) of 2-bromo-3-methoxy-6-nitropyridine was dissolved in 1700 mL of ethanol, and 37.3 g (50percent wet) of 10 percent palladium-carbon was added thereto under argon stream. To the mixture, 283 mL of hydrazine monohydrate was added dropwise. After the reaction mixture was refluxed for 70 minutes, the reaction solution was cooled to room temperature. Then, after palladium-carbon was filtered off, the residue was washed with ethanol, and the washing were combined with the filtrate. The combined solution was concentrated under reduced pressure. The, 1300 mL of water and 130 mL of conc. aqueous ammonia were added to the concentrate, and the resulting mixture was extracted eight times with chloroform. The combined chloroform layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was distilled under reduced pressure to obtain 26.2 g (corresponding to 0.211 mol) of 2-amino-5-methoxypyridine (

Reference： [1]Patent: EP2216051,2010,A1
[2]Patent: EP2216052,2010,A1

58
[ 107-20-0 ]
[ 10167-97-2 ]
[ 1044733-59-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3656 - 3660

59
[ 5324-15-2 ]
[ 10167-97-2 ]
[ 956500-13-3 ]

Yield	Reaction Conditions	Operation in experiment
		13.33 g (corresponding to 43.68 mmol) of 4'-benzoyloxy-2-bromoacetophenone and 5.67 g (corresponding to 45.67 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 481 mL of ethanol. The resulting solution was refluxed for 2 hours. After the reaction solution was cooled, 6.64 g (corresponding to 79.09 mmol) of sodium hydrogencarbonate was added thereto. The resulting reaction mixture was further refluxed for 4 hours. After the completion of the reaction, the solvent was concentrated under reduced pressure. The resulting residue was dissolved in chloroform and then washed with water. After the chloroform layer was dried over anhydrous sodium sulfate, the solvent was distilled off. The resulting crude product was purified by silica gel column chromatography (elution solvent: chloroform/ethyl acetate = 20/1), to obtain 10.20 g (corresponding to 30.87 mmol ) of 2-(4'-benzoyloxyphenyl)-6-methoxyimidazo[1,2-a]pyridine (Fig. 5, Step 5).
		, Step 4). 13.33 g (corresponding to 43.68 mmol) of 4'~ benzoyloxy-2-bromoacetophenone and 5.67 g (corresponding to 45.67 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 481 mL of ethanol. The resulting solution was refluxed for 2 hours. After the reaction solution was cooler, 6.64 g(corresponding to 79.09 mmol) of sodium hydrogencarbonate was added thereto. The resulting reaction mixture was further refluxed for 4 hours. After the completion of the reaction, the solvent was concentrated under reduced pressure. The resulting residue was dissolved in chloroform and then washed with water. After the chloroform layer was dried over anhydrous sodium sulfate, the solvent was distilled off. The resulting crude product was purified by silica gel column chromatography (elution solvent: chloroform/ethyl acetate = 20/1) to obtain 10.20 g (corresponding to 30.87 mmol) of 2-(4'-benzoyloxyphenyl)-6-methoxyimidazo[1,2-a]pyridine (
	With sodium hydrogencarbonate; In ethanol; chloroform;	, Step 4). 13.33 g (corresponding to 43.68 mmol) of 4'-benzoyloxy-2-bromoacetophenone and 5.67 g (corresponding to 45.67 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 481 mL of ethanol. The resulting solution was refluxed for 2 hours. After the reaction solution was cooled, 6.64 g (corresponding to 79.09 mmol) of sodium hydrogencarbonate was added thereto. The resulting reaction mixture was further refluxed for 4 hours. After the completion of the reaction, the solvent was concentrated under reduced pressure. The resulting residue was dissolved in chloroform and then washed with water. The chloroform layer was dried over anhydrous sodium sulfate, the solvent was distilled off. The resulting crude product was purified by silica gel column chromatography (elution solvent: chloroform/ethyl acetate = 20/1), to obtain 10.20 g (corresponding to 30.87 mmol) of 2-(4'-benzoyloxyphenyl)-6-methoxyimidazo[1,2-a]pyridine (

Reference： [1]Patent: EP2022792,2009,A1 .Location in patent: Page/Page column 11; 28
[2]Patent: EP2042501,2009,A1 .Location in patent: Page/Page column 9; 25
[3]Patent: EP2216051,2010,A1

60
[ 2491-38-5 ]
[ 10167-97-2 ]
[ 887576-96-7 ]

Yield	Reaction Conditions	Operation in experiment
		, Step 4). 2.15 g (corresponding to 10.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 1.25 g (corresponding to 10.0 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 50 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 90°C for 3.5 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 40 mL of water and 40mL of methanol. Then, about 20 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using a ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 1.96 g (corresponding to 8.16 mmol) of 2-(4'-hydroxyphenyl)-6-methoxyimidazo[1,2-a]pyridine ( 2.15 g (corresponding to 10.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 1.25 g (corresponding to 10.0 mmol) of 2-amino-5'-methoxypyridine were dissolved in 50 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 90°C for 3.5 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The recovered precipitates were washed with acetonitrile, and dried under reduced pressure to obtain crude crystals. The resulting crude crystals were suspended in a mixed solution of 40 mL of water and 40mL of methanol. The suspension was supplemented with about 20 mL of a saturated sodium hydrogencarbonate solution, and sonicated for 5 minutes by an ultrasonic washing machine. The precipitates were filtered and recovered from the resulting mixture, washed with water, and dried under reduced pressure, to obtain 1.96 g (corresponding to 8.16 mmol) of 2-(4'-hydroxyphenyl)-6-'methoxyimidazo[1,2-a]pyridine (Fig. 1, Step 5).
		645 mg (corresponding to 3.00 mmol) of 2-bromo-4'-hydroxyacetophenone and 372 mg (corresponding to 3.00 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was heated under reflux in an oil bath at 90°C for 2 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure to obtain crude crystals. The resulting crude crystals were suspended in a mixed solution of 4.0 mL of water and 4.0 mL of methanol. Then, about 2.0 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 512 mg (corresponding to 2.17 mmol) of 2-(4'-hydroxypheny)-6-methoxyimidazo[1,2-a]pyridine (Fig. 9, Step 5).

Reference： [1]Patent: EP2042501,2009,A1 .Location in patent: Page/Page column 8; 15; 24
[2]Patent: EP2213672,2010,A1 .Location in patent: Page/Page column 16; 27

61
[ 107-20-0 ]
[ 10167-97-2 ]
[ 955376-51-9 ]

Yield	Reaction Conditions	Operation in experiment
15 g	With sodium hydrogencarbonate; In methanol; water; for 2h;Reflux;	To a solution of 5-methoxypyridin-2-amine (15.0 g) in methanol (40 mL) and water (20 mL) was added 2-chloroacetaldehyde (25.0 g) and sodium bicarbonate (10.2 g). The mixture was stirred under reflux for 2 hours, and then concentrated. The residue was partionedbetween EA and aq. NaH CO3 solution. The organic layer was concentrated and purified by column chromatography to afford 6-methoxyimidazo[1 ,2-a]pyridine (15.0 g).

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 637 - 645
[2]Patent: WO2015/181186,2015,A1 .Location in patent: Page/Page column 131

62
[ 10167-97-2 ]
[ 16182-04-0 ]
[ 1092394-14-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 20℃;	Step A: 5-Methoxypyridin-2-amine ethoxycarbonyl thiourea To 5-methoxypyridin-2-amine (5 g, 40 mmol) in dioxane (40 mL) was added ethoxycarbonyl isothiocyanate (5.23 mL, 44.3 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo to afford 5-methoxypyridin-2-amine ethoxycarbonyl thiourea (10.28 g, 40.3 mmol, 100percent yield). 1H NMR (300 MHz, DMSO-d6) delta ppm 12.03 (1H, br. s.), 11.37 (1H, br. s.), 8.53 (1H, br. s.), 8.11 (1H, d, J=2.93 Hz), 7.50 (1H, dd, J=8.97, 3.11 Hz), 4.22 (2H, q, J=7.07 Hz), 3.84 (3H, s), 1.26 (3H, t, J=7.14 Hz). MS (LC/MS) R.T.=2.40; [M+H]+=256.1.
100%	at 20℃;	To 5-methoxypyridin-2-amine (5 g, 40 mmol) indioxane (40 mL) was added ethoxycarbonyl isothiocyanate(5.23 ml., 44.3 mmo1). The reaction mixture was stirred atroom temperature overnight. The mixture was concentratedin vacuo to afford 5-methoxypyridin-2-amine ethoxycarbonylthiourea(10.28 g, 40.3 mmol, 100percent yield).

Reference： [1]Patent: US2009/270405,2009,A1 .Location in patent: Page/Page column 81
[2]Patent: JP5714745,2015,B2 .Location in patent: Paragraph 0255; 0256

63
[ 10167-97-2 ]
[ 16182-04-0 ]
ethyl [(5-methoxypyridin-2-yl)carbamothioyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	In dimethyl sulfoxide; for 15h;	To a solution of 5-methoxypyridin-2-amine (1.05 g, 8.43 mmol) in dimethyl sulfoxide (5 mL) was added ethyl isothiocyanatoformate (1.44 g, 11.0 mmol), and the mixture was stirred for 15 hr. The reaction mixture was diluted with water, and extracted with ethyl acetate (*3) . The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was dried to give the title compound (1.34 g, 62percent) as a white solid. 1H-NMR (DMSOd5, 300 MHz) delta 1.26 (3H, t, J = 7.2 Hz), 3.84 (3H, s), 4.22 (2H, q, J = 7.2 Hz), 7.51 (IH, dd, J = 9.0, 3.0 Hz), 8.12 (IH, d, J = 3.0 Hz), 8.54 (IH, br s) , 11.38 (IH, br s), 12.04 (IH, br s) .

Reference： [1]Patent: WO2009/136663,2009,A1 .Location in patent: Page/Page column 161

64
[ 10167-97-2 ]
[ 6484-24-8 ]
[ 827031-75-4 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 2341 - 2351

65
[ 10167-97-2 ]
[ 1694-29-7 ]
[ 328062-49-3 ]

Yield	Reaction Conditions	Operation in experiment
46.6%	In 1,2-dimethoxyethane; at 20℃;Reflux;	A mixture of 2-amino-5-bromopyridine (5.0 g, 28.9 mmol), sodium methoxide (6.3 g, 116.6 mmol) and copper powder (1.85 g, 28.9 mmol) in methanol (30 mL) was heated in sealed tube for 48 h at 100° C. The reaction mixture was cooled to room temperature, diluted with dichloromethane (50 mL), filtered through a pad of celite and the filtrate was concentrated under reduced pressure. The residue was diluted with water, extracted with dichloromethane (2.x.100 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The crude material was purified over silica gel column chromatography eluting with EtOAc:Hexane (6:4) to afford Int-1 (1.2 g, 34.3percent) as brown color oil. To a solution of Int-1 (3.0 g, 24.2 mmol) in dimethoxy ethane (30 mL) was added 3-chloro-2,4-pentanedione (4.9 g, 36.4 mmol) at room temperature and the mixture was stirred at reflux temperature for 16 hours. The volatile was concentrated under reduced pressure. The residue was purified over silica gel column chromatography eluting with MeOH:DCM (1:9) to afford Int-2 (2.3 g, 46.6percent) as brown color oil. A solution of Int-2 (1.5 g, 7.35 mmol) in DMF DMA (15 mL) was stirred at reflux temperature for 24 hours. The reaction mixture was cooled to room temperature and diluted with diethyl ether (15 mL) and stirred for 15 minutes. The precipitated solid was filtered, washed with ether (2.x.10 mL) and dried under vacuum to afford Int-3 (1.2 g, 63percent) as brown solid. Mass (m/z): 260 [M++1]. 1H NMR (200 MHz, CDCl3): delta 9.43 (d, J=2.2 Hz, 1H), 7.8 (d, J=12.4 Hz, 1H), 7.44 (d, J=9.8 Hz, 1H), 7.09 (dd, J=2.2, 9.6 Hz, 1H), 5.58 (d, J=12 Hz, 1H), 3.86 (s, 3H), 3.06 (brs, 6H), 2.75 (s, 3H). To a solution of Int-3 (1.6 g, 6.17 mmol) in DMF (25 mL) was added Int-3B (2.38 g, 12.3 mmol) followed by K2CO3 (2.13 g, 15.4 mmol) at room temperature under inert atmosphere and the reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was cooled to room temperature, poured into ice water (70 mL) and stirred for 15 minutes. The precipitated solid was filtered, washed with water (2.x.10 mL) and dried under vacuum to afford Int-4 (1.2 g, 50percent) as brown solid. Mass (m/z): 390 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 10.13 (s, 1H), 9.17 (s, 1H), 8.59 (d, J=5.6 Hz, 1H), 8.-6.90 (m, 4H), 7.55 (d, J=10 Hz, 1H), 7.25-7.14 (m, 2H), 3.8 (s, 3H), 3.66 (s, 3H), 2.6 (s, 3H). A mixture of Int-4 (0.8 g, 2.05 mmol) and 4 N HCl (30 mL) was stirred at reflux temperature for 4 hours. The reaction mixture was cooled to room temperature and pH adjusted to about 5 using NaHCO3 and stirred for 20 minutes. The precipitated solid was filtered, washed with water (2.x.10 mL) and dried under vacuum to afford Int-5 (0.7 g, 90.9percent yield) as brown color solid. Mass (m/z): 376 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 10.29 (s, 1H), 9.18 (d, J=1.8 Hz, 1H), 8.72 (d, J=5.2 Hz, 1H), 8.-7.78 (m, 6H), 7.64 (dd, J=2.2, 10 Hz, 1H), 3.71 (s, 3H), 2.69 (s, 3H). To a stirred solution of Int-5 (0.7 g, 1.86 mmol) in DMF (10 mL) were added HOBt (0.25 g, 1.86 mmol), EDCI (0.71 g, 3.7 mmol), N-ethyldiisopropylamine (0.7 mL, 5.58 mmol) at 0° C. After being stirred for 10 minutes, and then added o-phenylenediamine (0.2 g, 1.86 mmol) to the reaction mixture at 0° C. The reaction mixture was warmed to room temperature and stirring was continued for 16 hours. The reaction mixture was poured into ice cold water (50 mL) and stirred for 10 minutes. The precipitated solid was filtered, washed with water (3.x.10 mL) and dried under vacuum. The crude material was purified over silica gel column chromatography eluting with 4percent MeOH/DCM to afford the title compound (0.27 g, 31.1percent yield) as off white solid. Mass (m/z): 465.2 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 10.02 (s, 1H), 9.53 (s, 1H), 9.18 (s, 1H), 8.59 (d, J=5.6 Hz, 1H), 7.86-7.98 (m, 4H), 7.60 (d, J=9.6 Hz, 1H), 7.13-7.25 (m, 3H), 6.85-7.0 (m, 1H), 6.75 (d, J=8.0 Hz, 1H), 6.45-6.61 (m, 1H), 4.86 (brs, 2H), 3.69 (s, 3H), 2.60 (s, 3H). 13C NMR (125 MHz, dmso-d6): delta 164.69, 159.26, 158.17, 156.83, 148.74, 146.45, 143.33, 143.03, 142.42, 128.49, 127.05, 126.55, 126.21, 123.65, 120.66, 118.59, 118.10, 116.37, 116.29, 116.15, 110.27, 110.15, 55.90, 16.36.

Reference： [1]Patent: US2010/29638,2010,A1 .Location in patent: Page/Page column 96

66
[ 107-20-0 ]
[ 10167-97-2 ]
6-methoxyimidazo[1,2-a]pyridine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In ethanol; water;Reflux;	7 Preparation of compound 7a: 6-Methoxyimidazo[1,2-a]pyridineA solution of 5-methoxypyridin-2-annine (5.0 g, 40.3 mmol) and chloroacetaldehyde (-55percent solution in water - 32 g, 200 mmol) in ethanol (200 ml_) was refluxed overnight. The solvent was removed under reduced pressure and the resultant brown oil was triturated using methanolic MTBE which gave the hydrochloride of the title compound 7a as a beige solid (5.7 g, 77percent yield). 1 H NMR (400 MHz, DMSO-d6) delta ppm 14.62 (br, 1 H), 8.70 (d, J = 2.3 Hz, 1 H), 8.24 (d, J = 1.5 Hz, 1 H), 8.15 (d, J = 2.0 Hz, 1 H), 7.90 (d, J = 9.8 Hz, 1 H), 7.71 (dd, J = 9.8, 2.3 Hz, 1 H), 3.89 (s, 3 H). LCMS 185 (M+1 ).

Reference： [1]Patent: WO2010/16005,2010,A1 .Location in patent: Page/Page column 88

67
[ 621-59-0 ]
[ 68498-54-4 ]
[ 10167-97-2 ]
[ 1187590-10-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 4790 - 4793

68
[ 33243-33-3 ]
[ 10167-97-2 ]
[ 118000-69-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In methanol; water; acetonitrile;	, Step 3). 844 mg (corresponding to 3.0 mmol) of 2-bromo-4 - bromoacetophenone and 378 mg (corresponding to 3.0 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 25 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 105°C for 3.5 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure to obtain crude crystals. The resulting crude crystals were suspended in a mixed solution of 7 mL of water and 7 mL of methanol. Then, about 7 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered, sufficiently washed with water, and dried under reduced pressure, to obtain 640 mg (corresponding to 2.11 mmol) of 2-(4 -bromophenyl)-6-methoxyimidazo[1,2-a]pyridine (

Reference： [1]Patent: EP2216052,2010,A1

69
[ 1207852-61-6 ]
[ 10167-97-2 ]
[ 1207852-44-5 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 3528 - 3530

70
[ 10167-97-2 ]
4-hydroxy-3-iodophenacyl bromide [ No CAS ]
[ 1147548-96-6 ]

Yield	Reaction Conditions	Operation in experiment
		680 mg (corresponding to 1.99 mmol) of 2-bromo-4'-hydroxy-3'-iodoacetophenone and 252 mg (corresponding to 2.03 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 15 mL of acetonitrile. The resulting solution was heated under reflux in an oil bath at 105°C for 4 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 5 mL of water and 5 mL of methanol. Then, about 5 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 435 mg (corresponding to 1.19 mmol) of 2-(4'-hydroxy-3'-iodophenyl)-6-methoxyimldazo[1,2-a]pyridine (Fig. 3, Step 6).

Reference： [1]Patent: EP2213671,2010,A1 .Location in patent: Page/Page column 9; 24

71
[ 129765-95-3 ]
[ 10167-97-2 ]
C₁₆H₂₅N₃O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3596 - 3600

72
[ 103-72-0 ]
[ 10167-97-2 ]
C₁₃H₁₃N₃OS [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 1010 - 1021

73
[ 10167-97-2 ]
[ 1266676-70-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 1010 - 1021

74
[ 10167-97-2 ]
[ 1266676-88-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 1010 - 1021

75
[ 10167-97-2 ]
[ 1266676-99-6 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 1010 - 1021

76
[ 10167-97-2 ]
[ 16182-04-0 ]
5-methoxypyridin-2-amine ethoxycarbonyl thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	In 1,4-dioxane; at 20℃;	Step A: 5-Methoxypyridin-2-amine ethoxycarbonyl thioureaTo 5-methoxypyridin-2-amine (5g, 40 mmol) in dioxane (40 mL) was added ethoxycarbonyl isothiocyanate (5.23 mL, 44.3 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo to afford 5-methoxypyridin-2-amine ethoxycarbonyl thiourea (10.28 g, 40.3 mmol, 100 percent yield). XH NMR (300 MHz, DMSO-i/6) delta ppm 12.03 (1 H, br. s.), 11.37 (1 H, br. s.), 8.53 (1 H, br. s.), 8.11 (1 H, d, J=2.93 Hz), 7.50 (1 H, dd, J=8.97, 3.11 Hz), 4.22 (2 H, q, J=7.07 Hz), 3.84 (3 H, s), 1.26 (3 H, t, J=7.14 Hz). MS (LC/MS) R.T. = 2.40; [M+H]+ = 256.1.

Reference： [1]Patent: WO2011/53292,2011,A1 .Location in patent: Page/Page column 129

77
[ 10167-97-2 ]
[ 1092394-15-4 ]

Reference： [1]Patent: WO2011/53292,2011,A1
[2]Patent: JP5714745,2015,B2
[3]Patent: WO2009/136663,2009,A1

78
[ 10167-97-2 ]
[ 1192813-28-7 ]

Reference： [1]Patent: WO2011/53292,2011,A1
[2]Patent: JP5714745,2015,B2

79
[ 10167-97-2 ]
[ 98-74-8 ]
[ 1313547-57-7 ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine; at 20℃; for 2h;	To a solution of 5-methoxypyridin-2-amine (200mg, 1.611 lmmol) in pyridine(4mL) was added 4-nitrobenzene-l-sulfonyl chloride (428mg, 1.9333mmol). The mixture was stirred at RT for two hours. The solvent was removed under reduced pressure to give a solid (260 mg, 52percent). The solid was purified by column chromatography to give N-(5- methoxypyridin-2-yl)-4-nitrobenzenesulfonamide. MS (ESI) m/z 308.3 [M-H]".

Reference： [1]Patent: WO2011/82400,2011,A2 .Location in patent: Page/Page column 61
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 9251 - 9264

80
C₆H₃BrCl₂N₂ [ No CAS ]
[ 10167-97-2 ]
[ 1224708-99-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4698 - 4701

81
[ 70-34-8 ]
[ 10167-97-2 ]
[ 1420044-38-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 744 - 749

82
[ 10167-97-2 ]
[ 1420044-50-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 744 - 749

83
[ 10167-97-2 ]
[ 1420044-63-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 744 - 749

84
[ 10167-97-2 ]
C₁₅H₁₆N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 744 - 749

85
[ 32807-28-6 ]
[ 10167-97-2 ]
[ 1434288-35-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	With polyphosphoric acid; at 100℃; for 2h;Sealed tube;	A mixture of methyl 4-chloroacetoacetate (636 mg, 4.23 mmol) and 5-methoxypyridin-2-amine (617 mg, 3.84 mmol) were heated at 100 °C in polyphosphoric acid (5 mL) in a sealed vial for 2 hours. NOTE: The viscosity of PPA makes stirring difficult; the reaction was stirred manually once hot to mix the contents. Once LCMS showed complete consumption of the starting material, the hot reaction mixture was diluted with water, transferred to a 250 mL flask and neutralized with solid NaHCO3. The resulting precipitate was collected by suction filtration, dissolved in ethyl acetate, and the solution dried over sodium sulfate. The solvent was evaporated and the residue was dissolved in dichloromethane and passed through a silica plug, eluting with dichloromethane. The solvent was evaporated to give 2-(chloromethyl)-7-methoxy-4H-pyrido[1,2-a]pyrimidin-4-one (673 mg, 78 percent) as a brown solid. LCMS (APCI, pos mode) M+1= 225 AMU. 1H NMR (400MHz, ACETONITRILE-d3): ppm 8.49 (d, J=2.5 Hz, 1H), 7.61 - 7.70 (m, 1H), 7.51 - 7.60 (m, 1H), 6.46 (s, 1H), 4.53 (s, 2H), 3.93 (s, 3H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3358 - 3363

86
[ 1312934-68-1 ]
[ 10167-97-2 ]
1,3-bis(4-methoxybenzyl)-5-[(5-methoxypyridin-2-yl)amino]pyrimidine-2,4(1H,3H)-dione [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 9137 - 9141

87
2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2,5-dioxoimidazolidin-4-yl]acetic acid [ No CAS ]
[ 10167-97-2 ]
2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2,5-dioxoimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%		Example 72 Preparation of 2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2,5-dioxoimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamide. TBTU (351 mg; 1.07 mmol; 1.5 eq) and DIPEA (248 muL; 1.42 mmol; 2 eq) were added to a suspension of 2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2,5-dioxoimidazolidin-4-yl]acetic acid (1-10) (275 mg; 0.71 mmol; 1 eq) in dioxane (10 mL). The reaction mixture was stirred at room temperature for 20 minutes. Then, 5-methoxypyridin-2-amine (132 mg; 1.07 mmol; 1.5 eq) in dimethylformamide (0.2 mL) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated to dryness. Saturated ammonium chloride (80 mL) was added and the aqueous layer was extracted with ethyl acetate (3 x 80 mL). The combined organic layers were washed with saturated sodium chloride (3 x 80 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. After trituration in diethyl ether/dichloromethane, the title compound 2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2,5-dioxoimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl) acetamide was obtained in 17percent yield (65.5 mg) as an orange solid. 1H-NMR (DMSO-d6): delta (ppm) 2.79 (m, 2H), 3.02 (dd, 1H, J = 16.5 Hz, 4.0 Hz), 3.24 (dd, 1H, J = 16.6 Hz, 4.5 Hz), 3.33 (m, 1H), 3.67 (m, 1H), 3.7 (s, 3H), 3.79 (s, 3H), 4.52 (t, 1H, J = 4.2 Hz), 6.84 (d, 2H, J = 8.4 Hz), 7.16 (d, 2H, J = 8.7 Hz), 7.38 (m, 5H), 7.99 (m, 2H), 10.63 (s, 1H); MS (ESI+): m/z = 493 [M+H]+.
17%		Example 72: Preparation of 2-[l-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]- 2,5-dioxoimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamide. TBTU (351 mg; 1.07 mmol; 1.5 eq) and DIPEA (248 mu 1-42 mmol; 2 eq) were added to a suspension of 2-[l-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2,5- dioxoimidazolidin-4-yl] acetic acid (T10) (275 mg; 0.71 mmol; 1 eq) in dioxane (10 mL). The reaction mixture was stirred at room temperature for 20 minutes. Then, 5- methoxypyridin-2-amine (132 mg; 1.07 mmol; 1.5 eq) in dimethylformamide (0.2 mL) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated to dryness. Saturated ammonium chloride (80 mL) was added and the aqueous layer was extracted with ethyl acetate (3 x 80 mL). The combined organic layers were washed with saturated sodium chloride (3 x 80 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. After trituration in diethyl ether/dichloromethane, the title compound 2-[l-(4- fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2,5-dioxoimidazolidin-4-yl]-N-(5- methoxypyridin-2-yl)acetamide was obtained in 17percent yield (65.5 mg) as an orange solid. 1H-NMR (DMSO-d6): delta (ppm) 2.79 (m, 2H), 3.02 (dd, 1H, J = 16.5 Hz, 4.0 Hz), 3.24 (dd, 1H, J = 16.6 Hz, 4.5 Hz), 3.33 (m, 1H) , 3.67 (m, 1H), 3.7 (s, 3H), 3.79 (s, 3H), 4.52 (t, 1H, J = 4.2 Hz), 6.84 (d, 2H, J = 8.4 Hz), 7.16 (d, 2H, J = 8.7 Hz), 7.38 (m, 5H), 7.99 (m, 2H), 10.63 (s, 1H); MS (ESI+): m/z = 493 [M+H]+ .

Reference： [1]Patent: EP2664616,2013,A1 .Location in patent: Paragraph 0159-0160
[2]Patent: WO2013/171281,2013,A1 .Location in patent: Page/Page column 86-87

88
2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5-oxo-2-sulfanylideneimidazolidin-4-yl]acetic acid [ No CAS ]
[ 10167-97-2 ]
2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5-oxo-2-sulfanylideneimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%		Example 83 Preparation of 2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5-oxo-2-sulfanylideneimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamide. TBTU (244 mg; 0.74 mmol; 1.5 eq) and DIPEA (170 muL; 0.99 mmol; 2 eq) were added to a solution of 2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5-oxo-2-sulfanylideneimidazolidin-4-yl]acetic acid (1-21) (200 mg; 0.50 mmol; 1 eq) in anhydrous dioxane (8 mL). The reaction mixture was stirred at room temperature for 30 minutes. 5-methoxypyridin-2-amine (124 mg; 0.99 mmol; 2 eq) in solution in dioxane (2 mL) was added and the reaction mixture was stirred at room temperature for 3 days. Saturated ammonium chloride (30 mL) was added and the aqueous layer was extracted with ethyl acetate (3 x 40 mL). The combined organic layers were washed with saturated sodium chloride (30 mL), filtered and evaporated to dryness. The crude was purified on silica gel using dichloromethane/ethyl acetate (90/10) as an eluent. The residue was triturated with diethyl ether to afford the title compound 2-[1-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5-oxo-2-sulfanylideneimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamide in 27percent yield (85 mg) as a yellow solid. 1H-NMR (Acetone-d6): delta (ppm) 2.98 (m, 1H), 3.11 (m, 1H), 3.28 (m, 1H), 3.5 (m, 1H), 3.74 (s, 3H), 3.78 (m, 1H), 3.84 (s, 3H), 4.32 (m, 1H), 4.65 (m, 1H), 6.86 (m, 2H), 7.25 (m, 4H), 7.38 (m, 1H), 7.45 (m, 2H), 7.96 (s, 1H), 8.11 (m, 1H), 9.6 (m, 1H); MS (ESI+): m/z = 508.9 [M+H]+.
27%		Example 83: Preparation of 2-[l-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5- oxo-2-sulfanylideneimia^zolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamMe^ - TBTU (244 mg; 0.74 mmol; 1.5 eq) and DIPEA (170 mu 0.99 mmol; 2 eq) were added to a solution of 2-[l-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5-oxo-2- sulfanylideneimidazolidin-4-yl]acetic acid (1-21) (200 mg; 0.50 mmol; 1 eq) in anhydrous dioxane (8 mL). The reaction mixture was stirred at room temperature for 30 minutes. 5-methoxypyridin-2-amine (124 mg; 0.99 mmol; 2 eq) in solution in dioxane (2 mL) was added and the reaction mixture was stirred at room temperature for 3 days. Saturated ammonium chloride (30 mL) was added and the aqueous layer was extracted with ethyl acetate (3 x 40 mL). The combined organic layers were washed with saturated sodium chloride (30 mL), filtered and evaporated to dryness. The crude was purified on silica gel using dichloro methane/ethyl acetate (90/10) as an eluent. The residue was triturated with diethyl ether to afford the title compound 2-[l-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-5-oxo-2- sulfanylideneimidazolidin-4-yl]-N-(5-methoxypyridin-2-yl)acetamide in 27percent yield (85 mg) as a yellow solid. 1H-NMR (Acetone-d6): delta (ppm) 2.98 (m, 1H), 3.11 (m, 1H), 3.28 (m, 1H), 3.53 (m, 1H), 3.74 (s, 3H), 3.78 (m, 1H), 3.84 (s, 3H), 4.32 (m, 1H), 4.65 (m, 1H), 6.86 (m, 2H), 7.25 (m, 4H), 7.38 (m, 1H), 7.45 (m, 2H), 7.96 (s, 1H), 8.11 (m, 1H), 9.6 (m, 1H); MS (ESI+): m/z = 508.9 [M+H]+ .

Reference： [1]Patent: EP2664616,2013,A1 .Location in patent: Paragraph 0203-0204
[2]Patent: WO2013/171281,2013,A1 .Location in patent: Page/Page column 107

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 10167-97-2 ]

Ethers

[ 89943-11-3 ]

5-Ethoxypyridin-2-amine

Similarity: 0.96

[ 10201-73-7 ]

2-Amino-4-methoxypyridine

Similarity: 0.84

[ 96166-00-6 ]

5-(Benzyloxy)pyridin-2-amine

Similarity: 0.81

[ 1221171-88-5 ]

5-(Trifluoromethoxy)pyridin-2-amine

Similarity: 0.81

[ 73101-79-8 ]

5-Ethoxy-6-methylpyridin-2-amine

Similarity: 0.81

Amines

[ 89943-11-3 ]

5-Ethoxypyridin-2-amine

Similarity: 0.96

[ 10201-73-7 ]

2-Amino-4-methoxypyridine

Similarity: 0.84

[ 33631-05-9 ]

2-Aminopyridin-4-ol

Similarity: 0.82

[ 1221171-88-5 ]

5-(Trifluoromethoxy)pyridin-2-amine

Similarity: 0.81

[ 73101-79-8 ]

5-Ethoxy-6-methylpyridin-2-amine

Similarity: 0.81

Related Parent Nucleus of
[ 10167-97-2 ]

Pyridines

[ 89943-11-3 ]

5-Ethoxypyridin-2-amine

Similarity: 0.96

[ 10201-73-7 ]

2-Amino-4-methoxypyridine

Similarity: 0.84

[ 33631-05-9 ]

2-Aminopyridin-4-ol

Similarity: 0.82

[ 1221171-88-5 ]

5-(Trifluoromethoxy)pyridin-2-amine

Similarity: 0.81

[ 73101-79-8 ]

5-Ethoxy-6-methylpyridin-2-amine

Similarity: 0.81

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 10167-97-2 ] {[proInfo.proName]}

Quality Control of [ 10167-97-2 ]

Related Doc. of [ 10167-97-2 ]

Product Details of [ 10167-97-2 ]

Calculated chemistry of [ 10167-97-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 10167-97-2 ]

Application In Synthesis of [ 10167-97-2 ]

[ 10167-97-2 ] Synthesis Path-Upstream 1~19

[ 10167-97-2 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 10167-97-2 ]

Ethers

Amines

Related Parent Nucleus of [ 10167-97-2 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 10167-97-2 ]

Related Parent Nucleus of
[ 10167-97-2 ]