[ CAS No. 6320-39-4 ] {[proInfo.proName]}

Name: 6320-39-4|3-Amino-4-hydroxypyridine|95%
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2D 3D

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Quality Control of [ 6320-39-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 6320-39-4 ]

Product Details of [ 6320-39-4 ]

CAS No. :	6320-39-4	MDL No. :	MFCD04114230
Formula :	C₅H₆N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OIIBRAGQGFLUFI-UHFFFAOYSA-N
M.W :	110.11	Pubchem ID :	233392
Synonyms :

Calculated chemistry of [ 6320-39-4 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	30.66
TPSA :	59.14 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.1 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.51
Log Po/w (XLOGP3) :	-0.18
Log Po/w (WLOGP) :	0.38
Log Po/w (MLOGP) :	-0.86
Log Po/w (SILICOS-IT) :	0.25
Consensus Log Po/w :	0.02

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.96
Solubility :	12.0 mg/ml ; 0.109 mol/l
Class :	Very soluble
Log S (Ali) :	-0.61
Solubility :	27.3 mg/ml ; 0.248 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.03
Solubility :	10.3 mg/ml ; 0.0938 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.23

Safety of [ 6320-39-4 ]

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

Application In Synthesis of [ 6320-39-4 ]

* 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 [ 6320-39-4 ]
Downstream synthetic route of [ 6320-39-4 ]

[ 6320-39-4 ] Synthesis Path-Upstream 1~5

1
[ 5435-54-1 ]
[ 6320-39-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In methanol; N,N-dimethyl-formamide at 20℃; for 4 h;	Step 2: 3-Amino-pyridin-4-ol 3-Nitro-pyridin-4-ol (20.0 g, 143 mmol) was suspended in 1000 ml methanol and 20 ml DMF. Palladium on charcoal (2.0 g, 10percent Pd) was added and the mixture was hydrogenated at ambient temperature for 4 hrs. The suspension was filtered and the solvent was evaporated. The desired product was obtained as a pink oil (26 g, quantitative).
100%	With hydrogen In methanol at 20℃; for 3 h;	a) Synthesis of 3-amino-pyridin-4-ol In a 1000 ml flask, 3-nitro-pyridin-4-ol (11.6 g, 82.8 mmol) was dissolved in methanol (800 ml), and then added 10percent palladium on active carbon (1.2 g, 10 w/w percent). The reaction mixture was stirred for 3 hours under hydrogen atmosphere at room temperature. The resulting reaction solution was filtered on celite and then evaporated under reduced pressure to obtain white solid (9.4 g, quantitative yield). ¹H-NMR (DMSO-d, 300 MHz); δ=7.34 (dd, J=6.5 Hz, 1.5 Hz, 1H), 7.13 (d, J=1.5 Hz, 1H), 5.99 (d, J=6.5 Hz, 1H), 4.53 (s, 2H), 3.90-2.90 (br s, 1H). MS (ESI); 111.1 (M⁺+1).
90%	With palladium on activated charcoal; hydrogen In methanol at 20℃;	4-Hydroxy-3-nitropyridine (2.8 g, 20.0 mmol) was dissolved in 150 mL of methanol and 280 mg of Pd/C was added.The air in the reaction flask was replaced with hydrogen, and hydrogen was continuously introduced, stirred at room temperature, and monitored by TLC until the reaction was completed.The reaction mixture was filtered under suction, the cake was washed with methanol, and the filtrate was collected and concentrated under reduced pressure.3-amino-4-hydroxypyridine obtained as a dark orange oily liquid(1.98g, 90percent).

Reference： [1] Patent: US2007/105891, 2007, A1, . Location in patent: Page/Page column 10
[2] Patent: US2011/28467, 2011, A1, . Location in patent: Page/Page column 15
[3] Patent: CN108373476, 2018, A, . Location in patent: Paragraph 0390-0394
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 24, p. 9742 - 9753
[5] Roczniki Chemii, 1955, vol. 29, p. 119,127[6] Chem.Abstr., 1955, p. 11643
[7] Angewandte Chemie, 1936, vol. 49, p. 486,488
[8] Journal of Heterocyclic Chemistry, 1990, vol. 27, # 3, p. 563 - 566
[9] Journal of Chemical and Engineering Data, 1980, vol. 25, # 2, p. 176 - 183
[10] Journal of Organic Chemistry, 1995, vol. 60, # 17, p. 5721 - 5725
[11] Patent: WO2007/70173, 2007, A2, . Location in patent: Page/Page column 93

2
[ 5435-54-1 ]
[ 6320-39-4 ]

Reference： [1] Patent: US6110929, 2000, A,

3
[ 101654-28-8 ]
[ 6320-39-4 ]

Reference： [1] Yakugaku Zasshi, 1956, vol. 76, p. 1388,1390, 1393[2] Chem.Abstr., 1957, p. 6634

4
[ 6320-39-4 ]
[ 149-73-5 ]
[ 273-56-3 ]

Reference： [1] Patent: WO2013/152063, 2013, A1, . Location in patent: Page/Page column 77

5
[ 6320-39-4 ]
[ 14036-06-7 ]
[ 273-56-3 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1990, vol. 27, # 3, p. 563 - 566

[ 6320-39-4 ] Synthesis Path-Downstream 1~88

1
[ 101654-28-8 ]
[ 6320-39-4 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1956,vol. 76,p. 1388,1390, 1393
Chem.Abstr.,1957,p. 6634

2
[ 1603-79-8 ]
[ 6320-39-4 ]
[ 73330-97-9 ]

Reference： [1]Journal of Chemical and Engineering Data,1980,vol. 25,p. 176 - 183

3
[ 6320-39-4 ]
[ 14036-06-7 ]
[ 273-56-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,1990,vol. 27,p. 563 - 566

4
[ 6320-39-4 ]
[ 108-24-7 ]
[ 78998-29-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,1990,vol. 27,p. 563 - 566

5
[ 6320-39-4 ]
[ 33142-21-1 ]
[ 499787-42-7 ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 8145 - 8152

6
[ 6320-39-4 ]
[ 3303-84-2 ]
[2-(4-hydroxy-pyridin-3-ylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

7
[ 6320-39-4 ]
[ 3400-45-1 ]
cyclopentanecarboxylic acid (4-hydroxy-pyridin-3-yl)-amide [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

8
[ 6320-39-4 ]
[ 23680-31-1 ]
[2-benzyloxy-1-(4-hydroxy-pyridin-3-ylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

9
[ 6320-39-4 ]
[ 79-31-2 ]
N-(4-hydroxy-pyridin-3-yl)-isobutyramide [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

10
[ 6320-39-4 ]
[ 65-85-0 ]
[ 104621-57-0 ]

Yield	Reaction Conditions	Operation in experiment
59%		Benzoic acid (2.015 g, 16.5 mmol) was dissolved in 60 mL of THF.Add EDCI (3.163g, 16.5mmol),HOAT (2.244 g, 16.5 mmol) and 3.5 mL of triethylamine,Stirring at room temperature for 2 h to obtain an activated ester;The reaction solution was concentrated under reduced pressure and the obtained solid residue was dissolved in 15% DMF.The <strong>[6320-39-4]3-amino-4-hydroxypyridine</strong> was dissolved in 25 mL of DMF and slowly added to a solution of the activated ester in DMF.The reaction solution was poured into 350 mL of water, extracted with EtOAc.The organic phase was dried with anhydrous sodium sThe residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1).N-(4-hydroxypyridin-3-yl)benzamide as a white solid(2.1g, 59%).

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004
[2]Patent: CN108373476,2018,A .Location in patent: Paragraph 0390-0392; 0395; 0396

11
[ 6320-39-4 ]
[ 109-52-4 ]
pentanoic acid (4-hydroxy-pyridin-3-yl)-amide [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

12
[ 6320-39-4 ]
[ 75-98-9 ]
N-(4-hydroxy-pyridin-3-yl)-2,2-dimethyl-propionamide [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

13
[ 6320-39-4 ]
[ 1004764-42-4 ]

Yield	Reaction Conditions	Operation in experiment
71%		A suspension of 4-(benzyloxy)benzoic acid x65 (10.0 g, 43.81 mmol, 1 eq) and N, N- dimethylformamide (0.5 ml) in dichloromethane at 0 0C is treated with oxalyl chloride (5.18 ml, 48.19 mmol, 1.1 eq). The mixture is left to warm up to room temperature. When gas evolution has stopped, half of the solvent is removed under reduced pressure, and the solution is added dropwise to a solution of <strong>[6320-39-4]3-aminopyridin-4-ol</strong> (4.82 g, 43.81 mmol, 1 eq) and triethylamine (12.15 ml, 87.62 mmol, 2 eq) in dichloromethane (300 ml). The mixture is stirred at 20 0C for 24 h and water (200 ml) is added. The aqueous phase is extracted with a 9:1 mixture of dichloromethane and methanol (2 x 300 ml). The combined organic layers are dried over magnesium sulfate and concentrated under reduced pressure. The residue is triturated with ethyl acetate (50 ml) and the resulting suspension is filtered off. The solid is dried at 40 0C in vacuo to yield 10 g of 4-(benzyloxy)-N-(4-hydroxypyridin-3- yl)benzamide x66. Yield: 71 %. LC-MS (MH+): 321.

Reference： [1]Patent: WO2008/12010,2008,A1 .Location in patent: Page/Page column 98

14
[ 6320-39-4 ]
2-isopropyl-oxazolo[4,5-c]pyridine [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

15
[ 6320-39-4 ]
2-tert-butyloxazolo[4,5-c]pyridine [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

16
[ 6320-39-4 ]
2-butyl-oxazolo[4,5-c]pyridine [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

17
[ 6320-39-4 ]
2-cyclopentyl-oxazolo[4,5-c]pyridine [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

18
[ 6320-39-4 ]
(2-oxazolo[4,5-c]pyridin-2-yl-ethyl)-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

19
[ 6320-39-4 ]
(2-benzyloxy-1-oxazolo[4,5-c]pyridin-2-yl-ethyl)-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004

20
[ 6320-39-4 ]
[ 34297-84-2 ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 9001 - 9004
[2]Patent: CN108373476,2018,A

21
[ 6320-39-4 ]
[ 120208-25-5 ]

Reference： [1]European Journal of Medicinal Chemistry,2005,vol. 40,p. 15 - 23
[2]Journal of Organic Chemistry,1995,vol. 60,p. 5721 - 5725
[3]Patent: WO2019/204550,2019,A1

22
[ 6320-39-4 ]
2-(4-propyl-piperazin-1-yl)-oxazolo[4,5-c]pyridine [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2005,vol. 40,p. 15 - 23

23
[ 6320-39-4 ]
[ 499787-43-8 ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 8145 - 8152

24
[ 6320-39-4 ]
ethyl 4-acetyl-4H-pyrido[4,3-b][1,4]oxazine-2-carboxylate [ No CAS ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 8145 - 8152

25
[ 6320-39-4 ]
[ 244274-96-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1999,vol. 47,p. 971 - 979

26
[ 6320-39-4 ]
[ 244274-98-4 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1999,vol. 47,p. 971 - 979

27
[ 6320-39-4 ]
[ 244275-00-1 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1999,vol. 47,p. 971 - 979

28
[ 6320-39-4 ]
3,4-dihydro-2,2-dimethyl-4-(2'-pyridyl)-2H-pyrido[4,3-b]-1,4-oxazine 6,1'-dioxide [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1999,vol. 47,p. 971 - 979

29
[ 6320-39-4 ]
[ 244274-99-5 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1999,vol. 47,p. 971 - 979

30
[ 6320-39-4 ]
[ 54459-88-0 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 8125 - 8131

31
[ 6320-39-4 ]
2-(1-Piperidinyl)oxazolo<4,5-c>pyridine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1995,vol. 60,p. 5721 - 5725

32
[ 6320-39-4 ]
[ 149301-73-5 ]
[ 288862-68-0 ]

Yield	Reaction Conditions	Operation in experiment
		1-(Oxazolo[4,5-c]pyridin-2-yl)arachidonaldehyde (39): 1-Hydroxy-1-(oxazolo[4,5-c]pyridin-2-yl)-5(Z),8(Z), 11(Z),14(Z)-eicosatetraene was prepared from arachidonyl aldehyde and <strong>[6320-39-4]3-amino-4-hydroxypyridine</strong> using method C3. This unstable alcohol was immediately oxidized using the procedure described for 18 to give 39.

Reference： [1]Patent: US6462054,2002,B1

33
[ 6320-39-4 ]
[ 141-75-3 ]
N-(4-hydroxypyrid-3-yl)butanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; water;	Part B N,N-diisopropylethylamine (33 mL, 180 mmol) was added to a suspension of <strong>[6320-39-4]3-aminopyridin-4-ol</strong> (8.5 g, 46 mmol) in dichloromethane (100 mL). A solution of butyryl chloride (5.4 g, 51 mmol) in dichloromethane (100 mL) was added dropwise. The reaction mixture was stirred at ambient temperature for 3 hours and then at reflux for 3 hours. The reaction mixture was filtered to remove a black precipitate. The filtrate was concentrated under vacuum. The resulting light brown residue was triturated with hot ethyl acetate (250 mL) and then allowed to cool overnight. The mixture was filtered to remove solids (9.1 g) and the solids were washed with fresh ethyl acetate. The filtrate was concentrated under vacuum to provide 13 g of a light amber syrup. The syrup was dissolved in water and then extracted twice with ethyl acetate. The extracts were combined, washed with brine, dried and then concentrated under vacuum to provide 2.5 g of an amber syrup. This material was purified by column chromatography to provide 1.2 g of N-(4-hydroxypyrid-3-yl)butanamide as a light amber syrup which solidified on standing.

Reference： [1]Patent: US6110929,2000,A

34
[ 5435-54-1 ]
[ 6320-39-4 ]
2-Propylpyrido[3,4-d][1,3]thiazole-5N-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride;aluminum nickel; In methanol; ethanol;	Example 61 2-Propylpyrido[3,4-d][1,3]thiazole-5N-oxide STR64 Part A A suspension of 3-nitropyridin-4-ol (1.0 g, 7.1 mmol) in methanol (110 mL) and a small amount of raney nickel catalyst were combined in a Parr bottle and hydrogenated for 4 hours. The reaction mixture was acidified with a solution of hydrochloric acid in ethanol and then filtered to remove catalyst. The filtrate was refiltered using Celite filter aid. The filtrate was concentrated under vacuum to provide 1.2 g of 3-aminopyridin-4-ol as a brown powder, m.p. 199-200 C.

Reference： [1]Patent: US6110929,2000,A

35
[ 288-32-4 ]
[ 5061-21-2 ]
[ 6320-39-4 ]
[ 15009-91-3 ]
[ 18162-48-6 ]
[ 191097-08-2 ]

Yield	Reaction Conditions	Operation in experiment
	With NaH; sodium acetate; trifluoroacetic acid;palladium-carbon; In chloroform; N,N-dimethyl-formamide;	4-(3-Chlorobenzyl)-3,4-dihydro-2-(2-hydroxyethyl)-3-oxo-2H-pyrido[4,3-b]-1,4-oxazine Freshly prepared 4-hydroxypyridine nitrate was nitrated by the procedure of D. Rasala and R. Gawinecki, Org. Prep. Proc. Int., 1985, 17, 409-423. An EtOH solution of this nitropyridine (1 eq) and NaOAc (1 eq) was reduced with 10% Pd/C (10% w/w) under a hydrogen atmosphere at 50 psig for 4 h. The crude <strong>[6320-39-4]3-amino-4-hydroxypyridine</strong> was dissolved in DMF (5 mL) and treated with NaH (1.2 eq). This mixture was then treated with alpha-bromo-gamma-butyrolactone (1.2 eq) at room temperature under nitrogen. After stirring at room temperature for 24 h, the DMF solution was treated with imidazole (1.2 eq) and t-butyldimethylsilyl chloride (1.2 eq). This solution was stirred for 16 h and then quenched with H2 O. The aqueous solution was extracted with EtOAc and the combined extract was washed with H2 O and dried over MgSO4. The EtOAc solution was filtered through SiO2 and concentrated under vacuum to afford the intermediate silyloxy compound in 14% yield. This material was alkylated by Method F, with 3-chlorobenzyl bromide, and then deprotected with TFA (20% v/v) in CHCl3 to afford the alcohol in 41% yield as a white crystalline solid; IR (KBr) 3519, 1664, 1393, 1320, 1192, 1082, 1054, 868 cm-1; 1 H NMR (DMSO-d6) delta1.97-2.09 (m, 2H), 3.58-3.62 (m, 2H), 4.75 (t, J=5.0, 1H), 5.10 (dd, J=8.5, 4.2 Hz, 1H), 5.21 (s, 2H), 7.07 (d, J=5.3 Hz, 1H), 7.25 (br d, J=6.8 Hz, 1H), 7.35-7.43 (m, 3H), 8.13 (d, J=5.8 Hz, 1H), 8.20 (s, 1H); MH+ at m/z=319.

Reference： [1]Patent: US5696117,1997,A

36
[ 6320-39-4 ]
[ 75-36-5 ]
[ 101860-99-5 ]

Yield	Reaction Conditions	Operation in experiment
35%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 3h;Heating / reflux;	Step 3: N-(4-Hydroxy-pyridin-3-yl)-acetamide 3-Amino-pyridin-4-ol (15.0, 136 mmol) was suspended in 200 ml dichloromethane and N-ethyldiisopropylamine (82 ml, 477 mmol) was added. A solution of acetylchloride (10.6 ml, 150 mmol) in 150 ml dichloromethane was added dropwise at ambient temperature. The reaction mixture was stirred at reflux for 3 hrs and evaporated to dryness. The residue was stirred in methanol and filtered. The solvent was evaporated and the desired product was obtained as a white solid (7.2 g, 35%), MS: m/e=151.1 (M+H+).

Reference： [1]Patent: US2007/105891,2007,A1 .Location in patent: Page/Page column 10

37
[ 6320-39-4 ]
[ 52833-94-0 ]
[ 1146633-79-5 ]

Yield	Reaction Conditions	Operation in experiment
	With PPA;	3-Aminopyridin-4-ol (2.90 g) and 2-amino-5-bromo-pyridine-3-carboxylic acid (5.72 g) were added to polyphosphoric acid (100 ml) and stirred at 200 C. for 5 hours. The reaction mixture was quenched with water (100 ml) and the mixture was basified with 10N sodium hydroxide until pH was 12.5. The resulting precipitate was collected by filtration, washed with water then methanol and dried under vacuum. There was thus obtained 5-bromo-3-(oxazolo[4,5-c]pyridin-2-yl)pyridin-2-amine (6.06 g);

Reference： [1]Patent: US2009/118305,2009,A1

38
[ 6320-39-4 ]
[ 7377-26-6 ]
[ 1154060-50-0 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In dichloromethane; at 0 - 20℃; for 60h;	A mixture of terephthalic acid monomethyl ester (7.20 g, 40 mmol), SOCl2 (60 ml) and DMF (50 mul) was stirred at reflux for 1 h. After removal of the excess SOCl2, the residue was azeotroped with toluene (3 ×) to remove the residual SOCl2. The crude acid chloride was dissolved in DCM (10 ml) and added dropwise at 0 C. to a solution of <strong>[6320-39-4]3-amino-4-hydroxypyridine</strong> (7.32 g, 40 mmol) in pyridine (40 ml). The reaction mixture was stirred at RT during 2.5 days. Pyridine was evaporated and water was added to the residue.The solid was filtered off, washed with water (3 ×), a mixture 1:3 of CH3CN-diethyl ether, diethyl ether and dried under vacuo at 60 C. to afford methyl 4-(4-hydroxypyridin-3-ylcarbamoyl)benzoate (9.70 g, 89%) which was used without further purification.1H NMR (DMSO-d6): delta 3.88 (s, 3H), 6.31 (d, 1H), 7.71 (d, 1H), 8.01 (d, 2H), 8.09 (d, 2 ), 8.75 (s, 1H), 9.43 (s, 1H).

Reference： [1]Patent: US2009/131468,2009,A1 .Location in patent: Page/Page column 25

39
[ 6320-39-4 ]
[ 7377-26-6 ]
methyl 4-(hydroxypyridin-3-ylcarbamoyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; at 20℃; for 60h;	A mixture of terephthalic acid monomethyl ester (7.20 g, 40 mmol), SOCl2 (60 ml) and DMF (50 mul) was stirred at reflux for Ih. After removal of the excess SOCl2, the residue was azeotroped with toluene (3 x) to remove the residual SOCl2. The crude acid chloride was dissolved in DCM (10 ml) and added dropwise at 0 0C to a solution of 3-amino-4- hydroxypyridine (7.32 g, 40 mmol) in pyridine (40 ml). The reaction mixture was stirred at RT during 2.5 days. Pyridine was evaporated and water was added to the residue. <n="39"/>The solid was filtered off, washed with water (3 x), a mixture 1 :3 of CH3CN - diethyl ether, diethyl ether and dried under vacuo at 60 0C to afford methyl 4-(4-hydroxypyridin-3- ylcarbamoyl)benzoate (9.70 g, 89%) which was used without further purification.1H NMR (DMSO-J6): delta 3.88 (s, 3H), 6.31 (d, IH), 7.71 (d, IH), 8.01 (d, 2H), 8.09 (d, 2H), 8.75 (s, IH), 9.43 (s, IH).

Reference： [1]Patent: WO2009/64251,2009,A1 .Location in patent: Page/Page column 36-37

40
[ 6320-39-4 ]
[ 1486-51-7 ]
[ 1004764-42-4 ]

Yield	Reaction Conditions	Operation in experiment
71%		16.1 Synthesis of 4-(benzyloxy)-N-(4-hydroxypyridin-3-yl)benzamide a50.A suspension of 4-(benzyloxy)benzoic acid a45 (10.0 g, 43.81 mmol, 1 eq) and N,N-dimethylformamide (0.5 ml) in dichloromethane at 00C is treated with oxalyl chloride (5.18 ml, 48.19 mmol, 1.1 eq). The mixture is left to warm up to room temperature. When gas evolution has stopped, half of the solvent is removed under reduced pressure, and the solution is added dropwise to a solution of 3-aminopyridin-4- ol (4.82 g, 43.81 mmol, 1 eq) and triethylamine (12.15 ml, 87.62 mmol, 2 eq) in dichloromethane (300 ml). The mixture is stirred at 200C for 24 h and water (200 ml) is added. The aqueous phase is extracted with a 9:1 mixture of dichloromethane and methanol (2 x 300 ml). The combined organic layers are dried over magnesium sulfate and concentrated under reduced pressure. The residue is triturated with ethyl acetate (50 ml) and the resulting suspension is filtered off. The solid is dried at 400C in vacuo to yield 10 g of 4-(benzyloxy)-N-(4-hydroxypyridin-3-yl)benzamide a50.Yield: 71 %. LC-MS (MH+): 321.

Reference： [1]Patent: WO2009/92764,2009,A1 .Location in patent: Page/Page column 80

41
[ 6320-39-4 ]
[ 941687-74-7 ]
[ 140-89-6 ]
[ 1257067-84-7 ]

Yield	Reaction Conditions	Operation in experiment
		Example 113-(1-[1,3]oxazolo[4,5-c]pyridin-2-ylpyrrolidin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile (One Enantiomer Isolated) A solution of <strong>[6320-39-4]3-aminopyridin-4-ol</strong> (0.250 g, 2.27 mmol, Bosche Scientific) and potassium O-ethyl dithiocarbonate (0.400 g, 2.50 mmol) in ethanol (1 mL) was heated to reflux. When the reaction was determined complete, it was cooled to ambient temperature and partitioned between 1N HCl and ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, decanted and concentrated. This crude product was dissolved in toluene (6 mL) and thionyl chloride (0.365 mL, 5.01 mmol) followed by DMF (3 microL) was added. The mixture was heated to reflux for 1 h, cooled and the solvent removed in vacuo. A portion of this crude product (14 mg) was dissolved in 1,4-dioxane (0.40 mL), along with 3-pyrrolidin-3-yl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile (20.0 mg, 0.0457 mmol, enantiomer 2 from Example 9, Step 2b), and N,N-diisopropylethylamine (16 microL, 0.091 mmol) was added. The mixture was heated to 70 C. for 1.5 h. The solvent was removed in vacuo and the residue was sequentially stirred with 50% TFA/DCM for 1.5 h, concentrated, and stirred with 0.3 mL EDA in methanol for 30 min. Purification via preparative-HPLC/MS (C18 column eluting with a gradient of ACN/H2O containing 0.15% NH4OH) afforded product. 1H NMR (400 MHz, d6-DMSO): delta 8.89 (s, 1H), 8.68 (s, 1H), 8.44 (s, 1H), 8.11 (dd, 1H), 7.72 (dd, 1H), 7.60 (d, 1H), 6.99 (d, 1H), 6.96 (dd, 1H), 4.88 (dt, 1H), 3.90 (dd, 1H), 3.71-3.63 (m, 1H), 3.58-3.30 (m, 4H), 3.04-2.93 (m, 1H), 1.80-1.66 (m, 2H); LCMS (M+H)+: 426.1.

Reference： [1]Patent: US2010/298334,2010,A1 .Location in patent: Page/Page column 40

42
[ 6320-39-4 ]
[ 79-04-9 ]
[ 102226-40-4 ]

Yield	Reaction Conditions	Operation in experiment
53%		b) Synthesis of 4H-pyrido[4,3-b][1,4]oxazin-3-one In a 500 ml flask equipped with a reflux apparatus, 3-amino-pyridin-4-ol (7.8 g, 71 mmol) was dissolved in N,N-dimethyl formamide (350 ml). To the reaction solution was added chloroacetyl chloride (6.2 ml, 78 mmol) dropwise at room temperature and then stirred at room temperature for 30 minutes. Potassium carbonate (24 g, 177 mmol) was added thereto and the mixture was heated at 100 for 40 hours. After completion of the reaction, water was added thereto. The mixture was extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and evaporated under reduced pressure. The residue was purified by recrystallizing from solvents of ethyl acetate and n-hexane to obtain white solid (5.6 g, 53%). 1H-NMR (DMSO-d6, 300 MHz); delta=10.90 (s, 1H), 8.06-8.04 (m, 2H), 6.96 (d, J=5.3 Hz, 1H), 4.71 (s, 2H). MS (ESI); 150.8 (M++1).

Reference： [1]Patent: US2011/28467,2011,A1 .Location in patent: Page/Page column 15

43
[ 6320-39-4 ]
[ 5424-01-1 ]
[ 1307233-72-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	<strong>[6320-39-4]3-Amino-4-hydroxypyridine</strong> (14.29 g, 129.8 mmol) and 3-aminopyrazine-2-carboxylic acid (18.05 g, 130 mmol) were mixed in DMF (350 mL). Triethylamine (51 mL, 364 mmol) and O-benzotriazol-1-yl-N,N,N',N'-tetra-methyluronium tetrafluoroborate (50.0 g, 155.7 mmol) were added and the mixture was stirred at RT under argon atmosphere overnight. The mixture was combined with a reaction mixture run under the same conditions as above. The solid formed was isolated by filtration and was washed with two portions of dichloromethane. The solid was dried under vacuum to give the title compound (32.35 g, 140 mmol, 54%). There was a precipitate in the mother liquor. The solid was isolated by filtration. The solid was washed with dichloromethane and was dried under vacuum to give the title compound (1.27 g, 5.49 mmol, 2%). There was a precipitate in the mother liquor. The solid was isolated by filtration. The solid was washed with dichloromethane and was dried under vacuum to give the title compound (3.29 g, 14.2 mmol, 6%). There was a precipitate in the mother liquor. The solid was isolated by filtration. The solid was washed with dichloromethane and was dried under vacuum to give the title compound (7.02 g, 30.4 mmol, 11%).Total yield of 3-amino-N-(4-hydroxypyridin-3-yl)pyrazine-2-carboxamide (43.9 g, 73%).MS (ESI+) m/z 232 [M+H]+.1H NMR (400 MHz, DMSO-d6) delta ppm 11.63 (br. s., 1H) 10.55 (s, 1H) 8.80 (d, 1H) 8.30 (d, 1H) 7.93 (d, 1H) 7.71 (dd, 1H) 7.61 (br. s., 2H) 6.29 (d, 1H).

Reference： [1]Patent: US2011/118275,2011,A1 .Location in patent: Page/Page column 11

44
[ 6320-39-4 ]
[ 486424-37-7 ]
[ 1307233-75-5 ]

Yield	Reaction Conditions	Operation in experiment
84.5%		-Amino-6-bromopyrazine-2-carboxylic acid (53.59 g, 0.229 mol) and 4-hydroxy-3-aminopyridine (33.64 g, 0.275 mol) were mixed in THF (500 mL) and triethyl amine (115.86 g, 1.145 mol) was added. The mixture was stirred at 25 for 10 min. The temperature was raised to 55 C. and T3P (218.90 g, 0.344 mol) was added. The mixture was stirred at 55 C. for 30 min. Water (150 mL) was added at 55 C. and the mixture was stirred for 2 h at 55 C. Solvents were distilled of until fractions at 55-80 C. was removed.Acetonitrile (500 mL) was added followed by water (350 mL) while maintaining the temperature at 75 C. The mixture was stirred for 2 h at 75 C. The solid was isolated by filtration. The solid was washed with water (250 mL) followed by acetonitrile (250 mL). The solid was dried under vacuum at 80 C. for 5 h to give the title compound (84.5%)1HNMR (400 MHz, DMSO-d6): 11.64 (s, 1H) 10.26 (s, 1H) 8.78 (s, 1H) 8.45 (s, 1H) 7.78 (s, 2H) 7.72 (d, 1H) 6.31 (d, 1H).MS (ESI+) m/z 310 [M+H]+

Reference： [1]Patent: US2011/118275,2011,A1 .Location in patent: Page/Page column 12

45
[ 6320-39-4 ]
[ 1307233-64-2 ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

46
[ 6320-39-4 ]
[ 1307233-44-8 ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

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[ 6320-39-4 ]
[ 1307233-53-9 ]

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[2]Patent: US2011/118275,2011,A1

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[ 6320-39-4 ]
[ 1307233-46-0 ]

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[2]Patent: US2011/118275,2011,A1

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[ 6320-39-4 ]
[ 1307233-50-6 ]

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[2]Patent: US2011/118275,2011,A1

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[ 6320-39-4 ]
[ 1307233-73-3 ]

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[ 6320-39-4 ]
[ 1307233-74-4 ]

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[2]Patent: US2011/118275,2011,A1

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[ 6320-39-4 ]
[ 1307233-76-6 ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

53
[ 6320-39-4 ]
(4-(5-Amino-6-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-yl)phenyl)(4-methylpiperazin-1-yl)methanone sulfate [ No CAS ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

54
[ 6320-39-4 ]
(4-(5-Amino-6-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-yl)phenyl)(4-methylpiperazin-1-yl)methanone maleate [ No CAS ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

55
[ 6320-39-4 ]
[ 1307233-62-0 ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

56
[ 6320-39-4 ]
[ 1307233-67-5 ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

57
[ 6320-39-4 ]
[ 1307233-69-7 ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

58
[ 6320-39-4 ]
[ 1307233-70-0 ]

Reference： [1]Patent: US2011/118275,2011,A1
[2]Patent: US2011/118275,2011,A1

59
[ 6320-39-4 ]
[ 88950-64-5 ]
[ 1334142-87-8 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	To a large screw cap vial was added <strong>[6320-39-4]3-aminopyridin-4-ol</strong> (0.440 g, 4.0 mmol) in DMF (lOmL) along with triethylamine (1.561 mL, 1 1.2 mmol), -(tert- butoxycarbonylamino)cyclopropanecarboxylic acid (0.845 g, 4.2 mmol) and finally TBTU, o-Benzotriazol-l-yl-N,N,N',N'-tetramethyluronium tetrafluoroborate (1.605 g, 5.0 mmol). The vial was sealed and the brown mixture was shaken for 24 hours at room temperature. The reaction mixture was concentrated to an oil, taken up in acetonitrile and purified using a Shimadzu preparative HPLC employingacetonitrile/water/ammonium acetate where solvent A was 5% acetonitrile / 95% water / 10 mM ammonium acetate and solvent B was 5% water / 95% acetonitrile / 10 mM ammonium acetate with a Phenomenex-Luna IotaOmicronmuiotaeta C18 30x100mm column at a gradient of 0-100% B and a flow rate of 30mL/min. over 10 minutes with a 5 minute hold. Solvent was removed giving l.Ogram (81% yield) of tert-butyl l-(4- hydroxypyridin-3-ylcarbamoyl) cyclopropyl carbamate as a light yellow solid. The LC/MS data was obtained on a Shimadzu analytical LC /Micromass Platform LC (ESI+) at 220nm using the following set of conditions: Phenomenex Luna 3muetaiota CI 8, 2 x 50mm column, with a gradient of 0-100%B (B = 90% HPLC grade acetonitrile/ 0.1% trifluoroacetic acid/ 10% HPLC grade water), (A = 90% HPLC grade water / 0.1% trifluoroacetic acid/ 10% HPLC grade acetonitrile), in 4 minutes with a 1 minute hold at a rate of 0.8 mL/minute. HPLC purity was determined using a Shimadzu analytical LC at 254nm and 256nm with a Waters Sunfire CI 8 3.5muiotaeta 4.6 x 150mm column employing water/acetonitrile/ 0.1% trifluoroacetic acid with a gradient of 10-100% B (B = 95% HPLC grade acetonitrile/ 0.1% trifluoroacetic acid/ 5% HPLC grade water), (A = 95% HPLC grade water / 0.1% trifluoroacetic acid/ 5% HPLC grade acetonitrile), in 10 minutes with a 10 minute hold at a rate of 1 mL/minute. The HPLC purity was then confirmed with an orthogonal solvent system and column using a Shimadzu analytical LC with a Phenomenex Gemini CI 8 3.0muiotaeta 4.6 x 150mm column employing water/methanol/ lOmM ammonium bicarbonate with a gradient of 10-100%) B (B = 95% HPLC grade methanol/ lOmM ammonium bicarbonate / 5% HPLC grade water), (A = 95% HPLC grade water / lOmM ammonium bicarbonate / 5% HPLC grade methanol), in 10 minutes with a 10 minute hold at a rate of 1 mL/minute. XH NMR (400 MHz, CD3OD) delta ppm 1.17 (m, 2 H), 1.51 (s, 9 H), 1.59 (m, 2 H), 6.55 (d, J=7.03 Hz, 1 H), 7.74 (dd, J=7.03, 1.51 Hz, 1 H), 7.79 (br. s., 1 H), 8.89 (d, 1 H). LCMS rt =1.682, min., m/z 294.3(M + H). HPLC rt = 5.621min. (Sunfire C18), 94.9% purity and 7.961min. (Gemini C18), 100 % purity

Reference： [1]Patent: WO2011/112769,2011,A1 .Location in patent: Page/Page column 46; 47

60
[ 6320-39-4 ]
[ 1334142-89-0 ]

Reference： [1]Patent: WO2011/112769,2011,A1

61
[ 6320-39-4 ]
1-(oxazolo[4,5-c]pyridin-2-yl)cyclopropanamine dihydrochloride [ No CAS ]

Reference： [1]Patent: WO2011/112769,2011,A1

62
[ 6320-39-4 ]
[ 1334142-61-8 ]

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[ 6320-39-4 ]
[ 1334142-62-9 ]

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64
[ 6320-39-4 ]
[ 1334142-63-0 ]

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65
[ 6320-39-4 ]
[ 1334142-64-1 ]

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[ 6320-39-4 ]
[ 1334142-65-2 ]

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67
[ 6320-39-4 ]
[ 1334142-66-3 ]

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68
[ 6320-39-4 ]
[ 1334142-67-4 ]

Reference： [1]Patent: WO2011/112769,2011,A1

69
[ 6320-39-4 ]
[ 586-75-4 ]
[ 934331-03-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 16h;	2-(4-Bromo-phenyl)-oxazolo[4,5-c] pyridine (17, Rb=H). To a cooled (0C) suspension of commercially available 4-hydroxy-3-amino-pyridine 14 (4g, 36mmol) in DCM (200ml) were added triethyl amine (6.3ml, 1.25eq) and a solution of 4-bromo-benzoyl chloride (15, Rb=H, 8g, 36mmol, leq, 0.3M in DCM). The reaction mixture was allowed to reach room temperature and the mixture was stirred for 16hrs. The mixture was filtered, washed with DCM and ether to furnish crude 16 (Rb=H) as a solid material which was used in the next step without further purification. Hexachloroethane (10.2g, 43mmol, 2.5eq) was dissolved in DCM (150ml) and triphenyl phosphine (13.56g, 51,69mmol, 3eq) and triethyl amine (19.2ml, 137.8mmol, 8eq) was added. The mixture was stirred for 10 minutes at room temperature and crude compound 16 (Rb=H) was added slowly in 5 equal portions. The mixture was stirred at room temperature for 64 hrs after which time TLC analysis (DCM/MeOH, 97/3, v/v, Rf 0.3) revealed complete reaction. The solution was concentrated and the residue was suspended in DCM. The mixture was filtered and the residue washed with DCM and diethyl ether to give crude 17 (Rb=H) which was used in the next step without further purification.

Reference： [1]Patent: WO2012/4373,2012,A1 .Location in patent: Page/Page column 43-44

70
[ 6320-39-4 ]
[ 1486-51-7 ]
[ 1004764-43-5 ]

Yield	Reaction Conditions	Operation in experiment
	With trichloroacetonitrile; triphenylphosphine; In acetonitrile; at 0 - 80℃; for 16h;	2-(4-Benzyloxy-phenyl)-oxazolo[4,5-c] pyridine (25, Ra=Rb=H).To a cooled (0C) suspension of commercially available 4-hydroxy-3-amino-pyridine (14, 19.3g, 175mmol) in acetonitril (1500ml) was added 4-benzyloxy-benzoic acid (24, Ra=Rb=H, 40g, 175mmol), triphenylphosphine (142.5g, 543mmol, 3.1eq) and trichloroactomtril (54.5ml, 543mmol, 3.1eq). The reaction mixture was allowed to reach room temperature and the mixture was stirred for 16hrs at 80C. The mixture was concentrated in vacuo and the residues was dissolved in DCM and washed with 2N NaOH (3x). The combined water layers were extracted with DCM and the organic layers dried (NaaSCU) to give crude 25 (Ra=Rb=H) as oil which was used in the next step without further purification.

Reference： [1]Patent: WO2012/4373,2012,A1 .Location in patent: Page/Page column 48

71
[ 6320-39-4 ]
[ 934331-04-1 ]