[ CAS No. 128694-63-3 ] {[proInfo.proName]}

Name: 128694-63-3|1-Methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid|97%
Brand: Ambeed
SKU: A100707
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Quality Control of [ 128694-63-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 128694-63-3 ]

Product Details of [ 128694-63-3 ]

CAS No. :	128694-63-3	MDL No. :	MFCD02090853
Formula :	C₆H₅F₃N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	AQUQLOWJSBFHBD-UHFFFAOYSA-N
M.W :	194.11	Pubchem ID :	606540
Synonyms :

Calculated chemistry of [ 128694-63-3 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.33
Num. rotatable bonds :	2
Num. H-bond acceptors :	6.0
Num. H-bond donors :	1.0
Molar Refractivity :	35.45
TPSA :	55.12 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) :	-6.77 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.15
Log Po/w (XLOGP3) :	1.01
Log Po/w (WLOGP) :	2.29
Log Po/w (MLOGP) :	0.77
Log Po/w (SILICOS-IT) :	0.82
Consensus Log Po/w :	1.21

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-1.83
Solubility :	2.86 mg/ml ; 0.0147 mol/l
Class :	Very soluble
Log S (Ali) :	-1.76
Solubility :	3.4 mg/ml ; 0.0175 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.06
Solubility :	16.9 mg/ml ; 0.0869 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.75

Safety of [ 128694-63-3 ]

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

Application In Synthesis of [ 128694-63-3 ]

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

Upstream synthesis route of [ 128694-63-3 ]
Downstream synthetic route of [ 128694-63-3 ]

[ 128694-63-3 ] Synthesis Path-Upstream 1~6

1
[ 1236144-18-5 ]
[ 128694-63-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	at 20℃; for 24 h; Schlenk technique	To a 15 mL Schlenk charged with the compound 3 (1.5 mmol) was added 1N sodium hydroxide (2.5 mL) and the resulting mixture was stirred vigorously for 24 h. The reaction mixture was acidified by the addition of 6N HCl at 0 °C. The resulting solid was collected by filtration, dichloromethane was added to the resulting suspension. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over anhydrous Na₂SO₄and the solvent was removed under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc = 5:1 to 2:1) to afford the product 5 (275 mg, 95percent yield) as a white solid.

Reference： [1] Tetrahedron Letters, 2017, vol. 58, # 46, p. 4344 - 4347
[2] Angewandte Chemie - International Edition, 2013, vol. 52, # 24, p. 6255 - 6258

2
[ 71-48-7 ]
[ 638-38-0 ]
[ 79080-31-2 ]
[ 128694-63-3 ]

Yield	Reaction Conditions	Operation in experiment
96.8%	With sodium bromide In acetic acid	EXAMPLE 9 In a 100 ml of an autoclave made of Hasteroy C-276 were charged 50 ml of acetic acid, 8.2 g (50 mmole) of 1,5-dimethyl-3-trifluoromethylpyrazole, 0.249 g (1 mmole) of cobalt acetate, 0.123 g (0.5 mmole) of manganese acetate and 0.204 g (2 mmole) of sodium bromide, reaction and operation were carried out in the same manner as in Example 1. A conversion ratio of the starting 1,5-dimethyl-3-trifluoromethylpyrazole was 96.8percent, and a yield of 1-methyl-3-trifluoromethylpyrazole-5-carboxylic acid was 52.0percent.

Reference： [1] Patent: US5053517, 1991, A,

3
[ 154471-65-5 ]
[ 128694-63-3 ]

Reference： [1] Patent: WO2007/43677, 2007, A1, . Location in patent: Page/Page column 486-487

4
[ 905844-08-8 ]
[ 128694-63-3 ]

Reference： [1] Journal of Organic Chemistry, 2008, vol. 73, # 9, p. 3523 - 3529

5
[ 124-38-9 ]
[ 154471-65-5 ]
[ 128694-63-3 ]

Reference： [1] European Journal of Organic Chemistry, 2002, # 17, p. 2913 - 2920
[2] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 22, p. 4898 - 4906
[3] Patent: US2011/160188, 2011, A1, . Location in patent: Page/Page column 4; 11

6
[ 129768-30-5 ]
[ 128694-63-3 ]

Reference： [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 24, p. 6255 - 6258
[2] Tetrahedron Letters, 2017, vol. 58, # 46, p. 4344 - 4347

[ 128694-63-3 ] Synthesis Path-Downstream 1~87

1
[ 2835-78-1 ]
[ 128694-63-3 ]
2-Methyl-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (3-benzoyl-phenyl)-amide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1997,vol. 62,p. 5908 - 5919

2
[ 124-38-9 ]
[ 154471-65-5 ]
[ 128694-63-3 ]

Yield	Reaction Conditions	Operation in experiment
		Chemical synthesis of compound 16677. For synthesis of compound 16677, 1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic acid 3 (Scheme 1, FIG. 10) was prepared from commercially available compound 1 as previously described (Schlosser et al., (2002) Eur. J. Org. Chem. 2002(17), 2913-2920). Compound 3 (820 mg, 4.2 mmol) in dichloromethane (10 ml) was treated with oxalyl chloride (2.0 M in CH2Cl2, 8.5 mmol, 4.2 ml) and a catalytic amount of DMF. The reaction mixture was incubated at room temperature for 5 hours. Evaporation of solvent delivered yellow acyl chloride 4 in quantitative yield.

Reference： [1]European Journal of Organic Chemistry,2002,p. 2913 - 2920
[2]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4898 - 4906
[3]Patent: US2011/160188,2011,A1 .Location in patent: Page/Page column 4; 11

3
[ 128694-63-3 ]
[ 129768-24-7 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In hexane; for 2h;Heating / reflux;	A mixture of 0.19 g of l-methyl-3-trifluoromethyl- lH-pyrazole-5-carboxylic acid, 0.15 g of thionyl chloride and 5 ml of hexane was heated under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 0.14 g of l-methyl-3-trifluoromethyl-lH-pyrazole-5-carbonyl chloride. To a mixture of 0.22 g of N- (2-aminobenzoyl) -N' - ethoxycarbonylhydrazme and 10 ml of pyridine was added 0.14 g of the resulting l-methyl-3-trifluoromethyl-lH-pyrazole- 5-carbonyl chloride and the mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitates were collected by filtration to obtain 0.23 g of the present compound (3) of the formula :The present compound (3)1 H-NMR (DMSO-d6 ,TMS)delta(ppm) :1.20 (3H,t, J=8Hz) ,4.10 (2H,q, J=8Hz) ,4.19 (3H,s) ,7.17 (IH, s) ,7.28 (IH, t, J=8Hz) ,7.60 (IH, t, J=8Hz) ,7.79(lH,d, J=8Hz) ,8.37 (lH,d, J=8Hz) ,9.02 (lH,brs) ,10.41 (lH,brs) , 11.50(lH,brs)
	With thionyl chloride; In hexane; for 2h;Reflux;	Reference Example 3A mixture of 0.19 g of <strong>[128694-63-3]1-methyl-3-trifluoromethyl-1H-pyrazole-5-carboxylic acid</strong>, 0.15 g of thionyl chloride and 5 mL of hexane was heated to reflux for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 0.14 g of 1-methyl-3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride. To a mixture of 0.22 g of N-(2-aminobenzoyl)-N'-ethoxycarbonylhydrazine and 10 mL of pyridine was added 0.14 g of the resulting 1-methyl-3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride, and the mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a formed precipitate was collected by filtration to obtain 0.23 g of a compound I-(3). 1H-NMR (DMSO-d6, TMS) delta(ppm): 1.20 (3H, t, J=8 Hz), 4.10 (2H, q, J=8 Hz), 4.19 (3H, s), 7.17 (1H, s), 7.28 (1H, t, J=8 Hz), 7.60 (1H, t, J=8 Hz), 7.79 (1H, d, J=8 Hz), 8.37 (1H, d, J=8 Hz), 9.02 (1H, brs), 10.41 (1H, brs), 11.50 (1H, brs)
	With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 5h;	Chemical synthesis of compound 16677. For synthesis of compound 16677, <strong>[128694-63-3]1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic acid</strong> 3 (Scheme 1, FIG. 10) was prepared from commercially available compound 1 as previously described (Schlosser et al., (2002) Eur. J. Org. Chem. 2002(17), 2913-2920). Compound 3 (820 mg, 4.2 mmol) in dichloromethane (10 ml) was treated with oxalyl chloride (2.0 M in CH2Cl2, 8.5 mmol, 4.2 ml) and a catalytic amount of DMF. The reaction mixture was incubated at room temperature for 5 hours. Evaporation of solvent delivered yellow acyl chloride 4 in quantitative yield.

With thionyl chloride; In hexane; for 2h;Reflux;

A mixture of 0.19 g of <strong>[128694-63-3]1-methyl-3-trifluoromethyl-1H-pyrazole-5-carboxylic acid</strong>, 0.15 g of thionyl chloride and 5 mL of hexane was heated to reflux for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 0.14 g of 1-methyl-3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride. To a mixture of 0.22 g of N-(2-aminobenzoyl)-N'-ethoxycarbonylhydrazine and 10 mL of pyridine was added 0.14 g of the resulting 1-methyl-3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride, and the mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a formed precipitate was collected by filtration to obtain 0.23 g of a compound I-(3). 1H-NMR (DMSO-d6, TMS) delta (ppm): 1.20 (3H, t, J=8 Hz), 4.10 (2H, q, J=8 Hz), 4.19 (3H, s), 7.17 (1H, s), 7.28 (1H, t, J=8 Hz), 7.60 (1H, t, J=8 Hz), 7.79 (1H, d, J=8 Hz), 8.37 (1H, d, J=8 Hz), 9.02 (1H, brs), 10.41 (1H, brs), 11.50 (1H, brs)

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4898 - 4906
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203
[3]Antimicrobial Agents and Chemotherapy,2007,vol. 51,p. 2293 - 2303
[4]Patent: WO2007/43677,2007,A1 .Location in patent: Page/Page column 296-297
[5]Patent: US2010/99692,2010,A1 .Location in patent: Page/Page column 27
[6]Patent: US2011/160188,2011,A1 .Location in patent: Page/Page column 4; 11
[7]Journal of Heterocyclic Chemistry,2012,vol. 49,p. 1422 - 1424
[8]Patent: US2010/137314,2010,A1 .Location in patent: Page/Page column 25

4
[ 128694-63-3 ]
[ 949898-58-2 ]

Yield	Reaction Conditions	Operation in experiment
58%	With borane-THF; In tetrahydrofuran; at 20℃; for 3h;	Step 1: l-Methyl-3-(trifluoromethyl)-lH-pyrazol-5-yl] methanol Borane (1M in THF; 9.0 mL, 9.0 mmol) was added to a solution of l-methyl-5- (trifluoromethyl)pyrazole-3-carboxylic acid (350 mg, 1.8 mmol) in THF (10 mL) at rt. The mixture was stirred was stirred for 3 hours. It was then cooled to 0 C and quenched with water. The mixture was extracted with EtOAc (3x) and the combined organic layers were washed with brine, dried over Na2SC>4, filtered, and concentrated. The residue was purified on silica gel to afford [l-methyl-3-(trifluoromethyl)- lH-pyrazol-5-yi]methanol (188 mg; 58%) as a colorless oil. LCMS (FA): m/z = 18l (M+H).
		BB4; 5-(chloromethyl)-l-methyl-3-(trifluoromethyl)-lH-pyrazoleBB4a BB4b BB4Step A: l-Methyl-3-(trifluoromethyl)-lH-pyrazole-5-carboxylic acid BB4a (837 mg, 4.3 mmol) is dissolved in anhydrous tetrahydrofurane (10 mL), then LiAlH4 (2.16 mL of 2.0 M in tetrahydrofurane, 4.3 mmol) is added dropwise and stirred at rt for lh. The mixture is quenched by dropwise addition of IN HC1, then is made basic by addition of saturated NaHC03 and extracted with EtOAc (3x). The organic layers are combined, washed with brine, dried (MgS04), filtered and concentrated to provide (l-methyl-3-(trifluoromethyl)- lH-pyrazol-5-yl)methanol BB4b as a clear oil. 1H NMR (400 MHz, CDC13) delta = 6.46 (s, 1H), 4.69 (d, J = 5.6 Hz, 2H), 3.95 (s, 3H); MS calcd. for C6H8F3N20 ([M+H]+): 181.0, found: 181.1.

Reference： [1]Patent: WO2015/2994,2015,A2 .Location in patent: Paragraph 00187
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203
[3]Patent: WO2011/44001,2011,A1 .Location in patent: Page/Page column 34-35

5
[ 128694-63-3 ]
[ 481066-00-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203

6
[ 128694-63-3 ]
[ 949898-54-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203

7
[ 128694-63-3 ]
C₁₇H₂₀F₃N₃O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203

8
[ 128694-63-3 ]
[ 942060-05-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203

9
[ 128694-63-3 ]
C₁₆H₁₉F₃N₄O₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203

10
[ 128694-63-3 ]
C₁₆H₁₈F₃N₃O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5199 - 5203

11
[ 128694-63-3 ]
2-methyl-5-trifluoromethyl-2<i>H</i>-pyrazole-3-carboxylic acid (2-isopropylcarbamoyl-6-methyl-phenyl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4898 - 4906

12
[ 71-48-7 ]
[ 638-38-0 ]
[ 79080-31-2 ]
[ 128694-63-3 ]

Yield	Reaction Conditions	Operation in experiment
96.8%	With sodium bromide; In acetic acid;	EXAMPLE 9 In a 100 ml of an autoclave made of Hasteroy C-276 were charged 50 ml of acetic acid, 8.2 g (50 mmole) of 1,5-dimethyl-3-trifluoromethylpyrazole, 0.249 g (1 mmole) of cobalt acetate, 0.123 g (0.5 mmole) of manganese acetate and 0.204 g (2 mmole) of sodium bromide, reaction and operation were carried out in the same manner as in Example 1. A conversion ratio of the starting 1,5-dimethyl-3-trifluoromethylpyrazole was 96.8%, and a yield of 1-methyl-3-trifluoromethylpyrazole-5-carboxylic acid was 52.0%.

Reference： [1]Patent: US5053517,1991,A

13
[ 154471-65-5 ]
[ 128694-63-3 ]

Yield	Reaction Conditions	Operation in experiment
		To a mixture of 8.71 g of l-methyl-3-trifIuoromethyl-1H-' pyrazole and 130 ml of tetrahydrofuran was added dropwise 32 ml of a 2.0 mol/L lithium diisopropylamide solution in heptane/tetrahydrofuran/ethylbenzene at -78C. The mixture of stirred at -780C for 2 hours and then poured into a mixture was dry ice and 50 ml of tetrahydrofuran. The mixture was stirred for 2 hours while allowing it to rise to around room temperature. Water and diethyl ether were poured into the reaction mixture. The aqueous layer was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then layers were separated. The resulting aqueous layer was washed with diethyl ether two times, adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 8.19 g of l-methyl-3- tri f luoromethyl- lH-pyra zole- 5-carboxylic acid of the formula :l-Methyl-3-trifluoromethyl-lH-pyrazole-S-carboxylic acid EPO <DP n="488"/>1H-NMR (CDCl3, TMS) delta (ppm) : 4.13 (3H, s) , 7.22 (IH, s).

Reference： [1]Patent: WO2007/43677,2007,A1 .Location in patent: Page/Page column 486-487

14
[ 905844-08-8 ]
[ 128694-63-3 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 3523 - 3529

15
[ 128694-63-3 ]
[ 128694-71-3 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 3523 - 3529

16
[ 79-37-8 ]
[ 1005777-50-3 ]
[ 128694-63-3 ]
[ 1005780-64-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine; In tetrahydrofuran; N,N-dimethyl-formamide;	Example 112 Production of N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide Using <strong>[128694-63-3]1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid</strong> (100 mg, 0.515 mmol), N,N-dimethylformamide (1 drop), oxalyl chloride (60 muL, 0.7 mmol), N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (122.5 mg, 0.396 mmol), triethylamine (120 mg, 1.19 mmol) and tetrahydrofuran (15 mL) as starting materials and in the same manner as in Example 109, the title compound (149 mg, 78%) was obtained as a white powder. 1H-NMR (DMSO-d6, 300 MHz) delta 0.73-0.85 (4H, m), 1.84-1.97 (1H, m), 4.15 (3H, s), 7.05 (1H, m), 7.08 (1H, d, J=9.6 Hz), 7.46 (1H, t, J=8.2 Hz), 7.50 (1H, s), 7.59-7.64 (1H, m), 7.66 (1H, t, J=2.1 Hz), 7.98 (1H, s), 8.06 (1H, d, J=9.6 Hz), 10.53 (1H, s), 11.10 (1H, s).

Reference： [1]Patent: US2009/137595,2009,A1

17
[ 79-37-8 ]
[ 1005781-39-4 ]
[ 128694-63-3 ]
[ 1005785-51-2 ]

Yield	Reaction Conditions	Operation in experiment
77%	In tetrahydrofuran; N,N-dimethyl acetamide; N,N-dimethyl-formamide;	Example 310 Production of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-fluorophenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide In the same manner as in Example 259 and using <strong>[128694-63-3]1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid</strong> (150 mg, 0.79 mmol), tetrahydrofuran (5 mL), N,N-dimethylformamide (1 drop), oxalyl chloride (140 muL, 1.6 mmol), N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.61 mmol) and N,N-dimethylacetamide (7 mL) as starting materials, the title compound (240 mg, 77%) was obtained as a white solid. 1H-NMR (DMSO-d6, 300 MHz) delta 0.71-0.85 (4H, m), 1.85-1.97 (1H, m), 4.15 (3H, s), 7.09 (1H, d, J=9.4 Hz), 7.21-7.28 (1H, m), 7.39-7.47 (1H, m), 7.54 (1H, s), 7.58 (1H, dd, J=6.3, 2.9 Hz), 7.95 (1H, s), 8.05 (1H, d, J=9.4 Hz), 10.45 (1H, s), 11.08 (1H, s).

Reference： [1]Patent: US2009/137595,2009,A1

18
[ 79-37-8 ]
[ 1005780-53-9 ]
[ 128694-63-3 ]
[ 1005785-50-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	In tetrahydrofuran; N,N-dimethyl acetamide; N,N-dimethyl-formamide;	Example 309 Production of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide In the same manner as in Example 259 and using <strong>[128694-63-3]1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid</strong> (160 mg, 0.80 mmol), tetrahydrofuran (5 mL), N,N-dimethylformamide (1 drop), oxalyl chloride (170 muL, 2.0 mmol), N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.62 mmol) and N,N-dimethylacetamide (7 mL) as starting materials, the title compound (240 mg, 76%) was obtained as a white solid. 1H-NMR (DMSO-d6, 300 MHz) delta 0.74-0.86 (4H, m), 1.86-1.97 (1H, m), 2.27 (3H, s), 4.15 (3H, s), 7.05 (1H, d, J=9.6 Hz), 7.13 (1H, dd, J=8.3, 2.6 Hz), 7.30 (1H, d, J=2.6 Hz), 7.37 (1H, d, J=8.3 Hz), 7.49 (1H, s), 7.94 (1H, s), 8.04 (1H, d, J=9.6 Hz), 10.13 (1H, s), 11.08 (1H, s).

Reference： [1]Patent: US2009/137595,2009,A1

19
[ 128694-63-3 ]
[ 184358-63-2 ]

Reference： [1]Patent: WO2011/44001,2011,A1

20
[ 128694-63-3 ]
[ 1245771-97-4 ]

Yield	Reaction Conditions	Operation in experiment
		<Step 8-1 > Synthesis of 1-methyl-3-(trifluoromethyl)-1 H-pyrazole-5-carboxamide[0230] 1-Methyl-3-(trifluoromethyl)-1 H-pyrazole-5-carboxylic acid (4.85 g) and dimethylformamide (0.04 g) were dissolved in dichloromethane (80 ml), and a dichloromethane solution (20 ml) of oxalyl chloride (3.33 g) was dropped thereon. The mixture was stirred at room temperature for 1 hour, and then, the solvent was concentrated. The residue was dissolved in dichloromethane (15 ml), and a mixed solution of 28% ammonia water (15.2 g) and dichloromethane (25 ml) was added thereto at 0C. The mixture was stirred at room temperature for 1 hour, and then, the organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was concentrated to obtain crude 1-methyl-3- (trifluoromethyl)-1 H-pyrazole-5-carboxamide (4.29 g).

Reference： [1]Patent: WO2012/25460,2012,A1 .Location in patent: Page/Page column 48-49

21
[ 128694-63-3 ]
[ 1316223-15-0 ]

Reference： [1]Patent: WO2012/25460,2012,A1

22
[ 128694-63-3 ]
[ 1359996-85-2 ]

Reference： [1]Patent: WO2012/25460,2012,A1

23
[ 128694-63-3 ]
[ 1361979-68-1 ]

Reference： [1]Patent: WO2012/25460,2012,A1

24
[ 1033132-75-0 ]
[ 128694-63-3 ]
[ 1033132-80-7 ]