[ CAS No. 478968-48-8 ] {[proInfo.proName]}

Name: 478968-48-8|Ethyl 3-methoxy-1H-pyrazole-4-carboxylate|96%
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SKU: A417704
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Quality Control of [ 478968-48-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 478968-48-8 ]

CAS No. :	478968-48-8	MDL No. :	MFCD13689107
Formula :	C₇H₁₀N₂O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VXHCBKUFAXDEDI-UHFFFAOYSA-N
M.W :	170.17	Pubchem ID :	54415748
Synonyms :

Calculated chemistry of [ 478968-48-8 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.43
Num. rotatable bonds :	4
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.17
TPSA :	64.21 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) :	-6.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.35
Log Po/w (XLOGP3) :	0.74
Log Po/w (WLOGP) :	0.59
Log Po/w (MLOGP) :	0.18
Log Po/w (SILICOS-IT) :	1.09
Consensus Log Po/w :	0.79

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.41
Solubility :	6.69 mg/ml ; 0.0393 mol/l
Class :	Very soluble
Log S (Ali) :	-1.67
Solubility :	3.66 mg/ml ; 0.0215 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.84
Solubility :	2.47 mg/ml ; 0.0145 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.14

Safety of [ 478968-48-8 ]

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

Application In Synthesis of [ 478968-48-8 ]

* 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 [ 478968-48-8 ]
Downstream synthetic route of [ 478968-48-8 ]

[ 478968-48-8 ] Synthesis Path-Upstream 1~5

1
[ 478968-48-8 ]
[ 103626-03-5 ]

Reference： [1] Bioorganic and medicinal chemistry letters, 2002, vol. 12, # 16, p. 2105 - 2108

2
[ 77-78-1 ]
[ 478968-45-5 ]
[ 478968-48-8 ]

Reference： [1] Bioorganic and medicinal chemistry letters, 2002, vol. 12, # 16, p. 2105 - 2108
[2] Patent: WO2009/12482, 2009, A2, . Location in patent: Page/Page column 82-83

3
[ 7251-53-8 ]
[ 478968-48-8 ]

Reference： [1] Patent: WO2015/52264, 2015, A1,
[2] Patent: WO2016/128529, 2016, A1,

4
[ 178424-17-4 ]
[ 478968-48-8 ]

Reference： [1] Patent: WO2015/52264, 2015, A1,
[2] Patent: WO2016/128529, 2016, A1,

5
[ 87-13-8 ]
[ 478968-48-8 ]

Reference： [1] Patent: WO2016/128529, 2016, A1,

[ 478968-48-8 ] Synthesis Path-Downstream 1~87

1
[ 478968-48-8 ]
2-CN-[1,1'-biphenyl]-4'-(CH₂)-X [ No CAS ]
1-(2'-cyano-biphenyl-4-ylmethyl)-3-methoxy-1H-pyrazole-4-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

2
[ 77-78-1 ]
[ 478968-45-5 ]
[ 478968-48-8 ]

Yield	Reaction Conditions	Operation in experiment
		Step 3. Ethyl 3-methoxy-lH-pyrazole-4-carboxylate; <n="84"/>A mixture of ethyl l-acetyl-3 -hydroxy- lH-pyrazole-4-carboxylate (2.1 g, 10.6 mmol) and potassium carbonate (1.5 g, 10.6 mmol) in 45 mL of DMF is stirred at RT for 30 minutes. Dimethyl sulfate (1.0 mL, 10.6 mmol) in 25 mL of DMF is then added dropwise over 10 min, and the resulting reaction mixture is heated to 70 C for 4 h. The solvent is evaporated in vacuo, and the residue is dissolved in water and extracted with CH2CI2 (2 x 30 mL). The combined organic extracts are dried (Na2SO4), filtered, and evaporated in vacuo to give a yellow/brown oil. Purification by silica gel column chromatography (gradient from 50% EtOAc/hexane to 80% EtOAc/hexane) affords the title compound as a clear, viscous oil which slowly solidifies on standing.

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108
[2]Patent: WO2009/12482,2009,A2 .Location in patent: Page/Page column 82-83

3
[ 478968-48-8 ]
3-metoxy-1H-pyrazole-4-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

4
[ 478968-48-8 ]
[ 74-88-4 ]
[ 103626-04-6 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

5
[ 478968-48-8 ]
CH₂=CHCH₂-X [ No CAS ]
1-allyl-3-methoxy-1H-pyrazole-4-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

6
[ 478968-48-8 ]
(CH₃)2C=CHCH₂-X [ No CAS ]
3-methoxy-1-(3-methyl-but-2-enyl)-1H-pyrazole-4-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

7
[ 478968-48-8 ]
[ 103626-03-5 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

8
[ 478968-48-8 ]
[ 254909-11-0 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

9
[ 478968-48-8 ]
[ 113100-56-4 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

10
[ 478968-48-8 ]
3-methoxy-1-(3-methyl-but-2-enyl)-1H-pyrazole-4-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

11
[ 478968-48-8 ]
1-(2'-carboxy-biphenyl-4-ylmethyl)-3-methoxy-1H-pyrazole-4-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2105 - 2108

12
[ 1722-12-9 ]
[ 478968-48-8 ]
[ 1104275-43-5 ]

Yield	Reaction Conditions	Operation in experiment
		Step 4. Ethyl 3-methoxy-l-pyrimidin-2-yl-lH-pyrazole-4-carboxylate; Sodium hydride (60% in mineral oil, 528 mg, 13.2 mmol) is added portion wise to a solution of ethyl 3-methoxy-lH-pyrazole-4-carboxylate (1.5 g, 8.81 mmol) in 40 mL of THF at RT. Evolution of H2 (g) is observed. After about 5-10 min, 2-chloropyrirnidine (1.0 g, 8.81 mmol) is added, and the resulting reaction mixture is stirred at reflux for 15 h. After cooling to RT, the reaction is quenched with 10 mL of sat. NH4Cl and 10 mL of water and extracted with CH2Cl2 (2 x 40 mL). The combined organic extracts are dried (Na2SO4), filtered, and evaporated in vacuo to give a brown solid. Purification by silica gel column chromatography (gradient from 50% EtOAc/hexane to EtOAc) affords the title compound as a fluffy white solid.

Reference： [1]Patent: WO2009/12482,2009,A2 .Location in patent: Page/Page column 83

13
[ 436799-32-5 ]
[ 478968-48-8 ]
ethyl 3-methoxy-1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With copper(l) iodide; potassium carbonate; L-proline; In dimethyl sulfoxide; at 100℃;Inert atmosphere;	A mixture of CuT (122.93 mg, 0.65 mmol, 0.10 equiv), L-proline (148.8 mg, 1.29 mmol, 0.20 equiv), potassium carbonate (1.786 g, 12.92 mmol, 2.00 equiv), ethyl 3-methoxy-1H-pyrazole-4- carboxylate (1.1 g, 6.46 mmol, 1.00 equiv), and 5-bromo-2-(trifluoromethyl)pyridine (2.185 g, 9.67 mmol, 1.50 equiv) in DMSO (60 mL) was stuffed overnight at 100C under nitrogen. The reaction solution was diluted with water and extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel column with ethyl acetate/petroleum ether (1:6) to afford the title compound (790 mg, 39%) as a white solid.

Reference： [1]Patent: WO2015/52264,2015,A1 .Location in patent: Paragraph 01786; 01787

14
[ 799557-86-1 ]
[ 478968-48-8 ]
ethyl 3-methoxy-1-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With copper(l) iodide; potassium carbonate; L-proline; In N,N-dimethyl-formamide; at 100℃;Inert atmosphere;	[0765] A mixture of <strong>[478968-48-8]ethyl 3-methoxy-1H-pyrazole-4-carboxylate</strong> (200 mg, 1.18 mmol), CuT (23 mg,0.12 mmol), L-proline (28 mg, 0.24 mmol), 5-bromo-2-(trifluoromethyl)pyrimidine (320 mg, 1.41mmol), and potassium carbonate (407 mg, 2.95 mmol) in N,N-dimethylformamide (6 mL) was stirredovernight at 100C under nitrogen. The solid was filtered out and the liquid was concentrated. Theresidue was purified by a silica gel colunm eluting with dichloromethane to afford the title compound(210 mg, 57%) as a light yellow solid. LCMS [M+H]317; ?H NMR (300 MHz, CDC13) 3 9.21 (s, 2H),8.40 (s, 1H), 4.39-4.32 (m, 2H), 4.12 (s, 3H), 1.38 (t, J= 7.2 Hz, 3H).
39%	With copper(l) iodide; potassium carbonate; L-proline; In dimethyl sulfoxide; at 100℃;Inert atmosphere;	A mixture of CuT (88 mg, 0.46 mmol, 0.10 equiv), L-proline (108 mg, 0.94 mmol, 0.20 equiv), potassium carbonate (1.3 g, 9.41 mmol, 2.00 equiv), <strong>[478968-48-8]ethyl 3-methoxy-1H-pyrazole-4-carboxylate</strong> (800 mg, 4.70 mmol, 1.00 equiv), and 5-bromo-2-(trifluoromethyl)pyrimidine (1.28 g, 5.64 mmol, 1.20 equiv) in DMSO (5 mL) was stirred overnight at 100C under nitrogen. The reaction mixture was diluted with 40 mL of water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel column eluting with ethyl acetate/petroleum ether (1:5) to afford the title compound (580mg, 39%) as a white solid.
39%	With copper(l) iodide; potassium carbonate; L-proline; In dimethyl sulfoxide; at 100℃;Inert atmosphere;	A mixture of Cul (88 mg, 0.46 mmol, 0.10 equiv), L-proline (108 mg, 0.94 mmol, 0.20 equiv), potassium carbonate (1.3 g, 9.41 mmol, 2.00 equiv), ethyl 3-methoxy-li7-pyrazole-4-carboxylate (800 mg, 4.70 mmol, 1.00 equiv), and 5-bromo-2-(trifluoromethyl)pyrimidine (1.28 g, 5.64 mmol, 1.20 equiv) in DMSO (5 mL) was stirred overnight at 100 C under nitrogen. The reaction mixture was diluted with 40 mL of water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel column eluting with ethyl acetate/petroleum ether (1 :5) to afford the title compound (580mg, 39%) as a white solid.

Reference： [1]Patent: WO2016/128529,2016,A1 .Location in patent: Paragraph 0755; 0764; 0765
[2]Patent: WO2015/52264,2015,A1 .Location in patent: Paragraph 01617; 01618
[3]Patent: WO2018/15410,2018,A1 .Location in patent: Paragraph 0496-0499

15
[ 799557-87-2 ]
[ 478968-48-8 ]
ethyl 3-methoxy-1-[5-(trifluoromethyl)pyrazin-2-yl]-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With copper(l) iodide; potassium carbonate; L-proline; In N,N-dimethyl-formamide; at 100℃;Inert atmosphere;	A mixture of ethyl 3-methoxy- 1H-pyrazole-4-carboxylate (1.116 g, 6.56 mmol, 1.00 equiv) in N,N-dimethylformamide (60 mL), L-Proline (151 mg, 1.31 mmol, 0.20 equiv), CuT (128 mg, 0.67 mmol, 0.10 equiv), 2-chloro-5 -(trifluoromethyl)pyrazine (1.19 g, 6.52 mmol, 1.00 equiv), and potassium carbonate (2.72 g, 19.68 mmol, 3.00 equiv) was stuffed overnight at 100C under nitrogen. The solids were filtered out. The filtrate was diluted with 500 mL of ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column eluting with ethyl acetate/petroleum ether (5:100) to afford the title compound (1 g, 48%) as an off-white solid.

Reference： [1]Patent: WO2015/52264,2015,A1 .Location in patent: Paragraph 0867; 0868

16
[ 7251-53-8 ]
[ 478968-48-8 ]

Reference： [1]Patent: WO2015/52264,2015,A1
[2]Patent: WO2016/128529,2016,A1

17
[ 178424-17-4 ]
[ 478968-48-8 ]

Reference： [1]Patent: WO2015/52264,2015,A1
[2]Patent: WO2016/128529,2016,A1

18
1-tert-butyl 4-ethyl 3-methoxy-1H-pyrazole-1,4-dicarboxylate [ No CAS ]
[ 478968-48-8 ]

Yield	Reaction Conditions	Operation in experiment
71%	With trifluoroacetic acid; In dichloromethane; at 20℃; for 3h;	[0763] A mixture of 1-tert-butyl 4-ethyl 3-methoxy-1H-pyrazole-1,4-dicarboxylate (450 mg, 1.67 mmol) in dichloromethane (10 mL) and trifluoroacetic acid (3 mL) was stirred for 3 h at room temperature. The reaction mixture was concentrated under vacuum and diluted with water. The pH value of the mixture was adjusted to 8 with saturated aqueous sodium bicarbonate. The resulting mixture was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel colunm eluting with ethyl acetate/petroleum ether (1:5) to afford the title compound (200 mg, 71%) as light yellow oil. LCMS [M+H] 171.
69%	With hydrogenchloride; In 1,4-dioxane; at 20℃; for 5h;	A mixture of 1-tert-butyl 4-ethyl 3-methoxy-1H-pyrazole-1,4-dicarboxylate (16 g, 59.20 mmol, 1.00 equiv) and saturated hydrogen chloride in 1 ,4-dioxane (200 mL) was stuffed for 5 h at room temperature and concentrated under vacuum. The resulting solution was diluted with 20 mL of water and the pH value of the solution was adjusted to 8 by sodium bicarbonate. The resulting solution was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in the title compound (7 g, 69%) as brown oil.

Reference： [1]Patent: WO2016/128529,2016,A1 .Location in patent: Paragraph 0755; 0762; 0763
[2]Patent: WO2015/52264,2015,A1 .Location in patent: Paragraph 01661; 01662

19
[ 478968-48-8 ]
[3-methoxy-1-[5-(trifluoromethyl)pyrazin-2-yl]-1H-pyrazol-4-yl]methanol [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

20
[ 478968-48-8 ]
2-([3-methoxy-1-[5-(trifluoromethyl)pyrazin-2-yl]-1H-pyrazol-4-yl]methyl)-2,3-dihydro-1H-isoindole-1,3-dione [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

21
[ 478968-48-8 ]
[3-methoxy-1-[5-(trifluoromethyl)pyrazin-2-yl]-1H-pyrazol-4-yl]methanamine [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

22
[ 478968-48-8 ]
tert-butyl (2S,4R)-4-fluoro-2-[([3-methoxy-1-[5-(trifluoromethyl)pyrazin-2-yl]-1H-pyrazol-4-yl]methyl)carbamoyl]pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

23
[ 478968-48-8 ]
tert-butyl(2S,4S)-4-hydroxy-2-[([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl)carbamoyl]pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

24
[ 478968-48-8 ]
(2S,4S)-4-hydroxy-N-([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl)pyrrolidine-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

25
[ 478968-48-8 ]
(2S,4S)-1-[(4-fluorobenzene)sulfonyl]-4-hydroxy-N-([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl)pyrrolidine-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

26
[ 478968-48-8 ]
(3S,5S)-1-[(4-fluorobenzene)sulfonyl]-5-[([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl)carbamoyl]pyrrolidin-3-yl 4-methylbenzene-1-sulfonate [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

27
[ 478968-48-8 ]
(2S,4R)-4-cyano-1-[(4-fluorobenzene)sulfonyl]-N-([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl)pyrrolidine-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

28
[ 478968-48-8 ]
(2S,4R)-4-fluoro-1-[(4-fluorobenzene)sulfonyl]-N-([3-methoxy-1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazol-4-yl]methyl)-2-methylpyrrolidine-2-carboxamide [ No CAS ]
(2R,4R)-4-fluoro-1-[(4-fluorobenzene)sulfonyl]-N-([3-methoxy-1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazol-4-yl]methyl)-2-methylpyrrolidine-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

29
[ 478968-48-8 ]
3-methoxy-1-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyrazole-4-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1
[2]Patent: WO2018/15410,2018,A1

30
[ 478968-48-8 ]
3-methoxy-1-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyrazole-4-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1
[2]Patent: WO2018/15410,2018,A1

31
[ 478968-48-8 ]
3-methoxy-1-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyrazole-4-carbonitrile [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1
[2]Patent: WO2018/15410,2018,A1

32
[ 478968-48-8 ]
(2S,4R)-4-fluoro-1-[(3-fluorobenzene)sulfonyl]-N-([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl)pyrrolidine-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

33
[ 478968-48-8 ]
3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carbaldehyde [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

34
[ 478968-48-8 ]
[3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methanol [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

35
[ 478968-48-8 ]
(E)-N-([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methylidene)hydroxylamine [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

36
[ 478968-48-8 ]
[3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methanamine [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

37
[ 478968-48-8 ]
(2S,4R)-4-fluoro-1-[(4-fluorobenzene)sulfonyl]-N-([3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl)pyrrolidine-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

38
[ 478968-48-8 ]
[3-methoxy-1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazol-4-yl]methanol [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

39
[ 478968-48-8 ]
3-methoxy-1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazole-4-carbaldehyde [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

40
[ 478968-48-8 ]
[3-methoxy-1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazol-4-yl]methanamine [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

41
[ 478968-48-8 ]
(2S,4R)-4-fluoro-1-[(4-fluorobenzene)sulfonyl]-N-([3-methoxy-1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazol-4-yl]methyl)pyrrolidine-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2015/52264,2015,A1

42
[ 402-43-7 ]
[ 478968-48-8 ]
ethyl 3-methoxy-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With copper(l) iodide; potassium carbonate; L-proline; In dimethyl sulfoxide; at 100℃;Inert atmosphere;	A mixture of Cul (95 mg, 0.50 mmol, 0.10 equiv), L-proline (115 mg, 1.00 mmol, 0.20 equiv), potassium carbonate (1.38 g, 9.99 mmol, 2.00 equiv), <strong>[478968-48-8]ethyl 3-methoxy-1H-pyrazole-4-carboxylate</strong> (850 mg, 5.00 mmol, 1.00 equiv), and 1-bromo-4-(trifluoromethyl)benzene (2.04 g, 7.50 mmol, 1.50 equiv) in DMSO (10 mL) was stuffed overnight at 100C under nitrogen. The reaction was diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in the title compound (1.06g, 68%) as a white solid.

Reference： [1]Patent: WO2015/52264,2015,A1 .Location in patent: Paragraph 01663; 01664

43
[ 87-13-8 ]
[ 478968-48-8 ]

Reference： [1]Patent: WO2016/128529,2016,A1

44
[ 478968-48-8 ]
[3-methoxy-1-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyrazol-4-yl]methanol [ No CAS ]

Reference： [1]Patent: WO2016/128529,2016,A1

45
[ 478968-48-8 ]
5-[4-(chloromethyl)-3-methoxy-1H-pyrazol-1-yl]-2-(trifluoromethyl)pyrimidine [ No CAS ]

Reference： [1]Patent: WO2016/128529,2016,A1

46
[ 478968-48-8 ]
2-([3-methoxy-1-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyrazol-4-yl]methyl)-2,3-dihydro-1H-isoindole-1,3-dione [ No CAS ]

Reference： [1]Patent: WO2016/128529,2016,A1

47
[ 478968-48-8 ]
[3-methoxy-1-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyrazol-4-yl]methanamine [ No CAS ]

Reference： [1]Patent: WO2016/128529,2016,A1

48
3-chloro-6-(chloromethyl)quinoline [ No CAS ]
[ 478968-48-8 ]
ethyl 1-((3-chloroquinolin-6-yl)methyl)-3-methoxy-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	A mixture of ethyl 3-methoxy-lH-pyrazole-4-carboxylate (500 mg, 2.94 mmol, 1 eq), 3-chloro-6-chloromethyl-quinoline (744 mg, 3.6 mmol, 1.2 eq) and K2C03 (1.22 g, 8.84 mmol, 3.0 eq) in DMF (6 mL) was stirred at rt overnight. The mixture was concentrated and the resulting residue was diluted with water. The mixture was extracted with EA and the combined organic layers were dried and concentrated. The resulting residue was purified by chromatography on a silica gel column (PE/EA = 2/1, v/v) to afford ethyl l-((3-chloroquinolin-6-yl)methyl)-3-methoxy-lH-pyrazole-4-carboxylate (900 mg, 89%) as a white solid.

Reference： [1]Patent: WO2018/11628,2018,A1 .Location in patent: Paragraph 00331

49
[ 478968-48-8 ]
1-(3-chloroquinolin-6-ylmethyl)-3-methoxy-1H-pyrazole-4-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2018/11628,2018,A1

50
[ 478968-48-8 ]
N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-1-((3-chloroquinolin-6-yl)methyl)-3-methoxy-1H-pyrazole-4-carboxamide [ No CAS ]

Reference： [1]Patent: WO2018/11628,2018,A1

51
[ 478968-48-8 ]
1-[(6-{3-azabicyclo[3.1.0]hexan-3-yl}-2-methylpyridin-3-yl)methyl]-3-methoxy-1H-pyrazole-4-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Reference： [1]Patent: WO2018/192866,2018,A1

52
[ 478968-48-8 ]
N-[(5R)-1-amino-5H,6H,7H-cyclopenta[c]pyridin-5-yl]-1-[(6-{3-azabicyclo[3.1.0]hexan-3-yl}-2-methylpyridin-3-yl)methyl]-3-methoxy-1H-pyrazole-4-carboxamide [ No CAS ]

Reference： [1]Patent: WO2018/192866,2018,A1

53
[6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-methyl-pyridin-3-yl]-methanol [ No CAS ]
[ 478968-48-8 ]
ethyl 1-[(6-{3-azabicyclo[3.1.0]hexan-3-yl}-2-methylpyridin-3-yl)methyl]-3-methoxy-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tributylphosphine; di-tert-butyl-diazodicarboxylate; In tetrahydrofuran; at -10 - 20℃; for 0.5h;	(6-{3-Azabicyclo[3. 1 .0]hexan-3-yl}-2-methylpyridin-3-yl)methanol (410 mg), tributylphosphine (595 pL) and ethyl 3- methoxy-1H-pyrazole-4-carboxylate (340 mg) are dissolved in tetrahydrofuran (10 mL), cooled to -10 00 and treated with di-tert.-butyl azodicarboxylate (DBAD, 510 mg). Then the mixture is stirred for 30 minutes at room temperature. The mixture is purified by HPLC on reversed phase (acetonitrile, water, ammonia) to give the title compound.LC (Method 8): tR = 1.09 mm; Mass spectrum (ESIj: mlz = 357 [M+H].

Reference： [1]Patent: WO2018/192866,2018,A1 .Location in patent: Page/Page column 67; 68

54
[ 478968-48-8 ]
1-cyclopropyl-3-methoxy-1H-pyrazole-4-carboxylic acid [ No CAS ]

Reference： [1]Patent: US2019/352271,2019,A1

55
[ 1493-03-4 ]
[ 478968-48-8 ]
ethyl 1-(difluoromethyl)-3-methoxy-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In 1,4-dioxane; water; for 0.5h;	To a suspension of <strong>[478968-48-8]ethyl 3-methoxy-1H-pyrazole-4-carboxylate</strong> (350 mg, 2.05 mmol) in dioxane (1 mL) and water (0.7 mL), was added KOH (346 mg, 6.17 mmol). To stirred mixture was bubbled CHIF2 gas over 30 min. Two Regioisomer products were formed with same Mass at 221 (RT=0.39 and 0.49). The reaction mixture was diluted with ether (50 mL), washed with water followed by brine solution. The organic extract was dried over sodium sulfate to give crude product which was carried onto the next step without purification. LCMS-ESI+(m/z): [M+H] Calculated for C8H11F2N3O2: 220.08; found 220.90.

Reference： [1]Patent: US2019/352271,2019,A1 .Location in patent: Paragraph 0972-0973

56
[ 478968-48-8 ]
1-(difluoromethyl)-3-methoxy-1H-pyrazole-4-carboxylic acid [ No CAS ]

Reference： [1]Patent: US2019/352271,2019,A1

57
[ 478968-48-8 ]
[ 411235-57-9 ]
ethyl 1-cyclopropyl-3-methoxy-1H-pyrazole-4-carboxylate [ No CAS ]