[ CAS No. 17827-61-1 ] {[proInfo.proName]}

Name: 17827-61-1|Methyl 1-Methylpyrazole-3-carboxylate|98%
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Quality Control of [ 17827-61-1 ]

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Product Details of [ 17827-61-1 ]

CAS No. :	17827-61-1	MDL No. :	MFCD04967358
Formula :	C₆H₈N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WUUOFOYBXXQAGD-UHFFFAOYSA-N
M.W :	140.14	Pubchem ID :	7017175
Synonyms :

Safety of [ 17827-61-1 ]

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 [ 17827-61-1 ]

* 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 [ 17827-61-1 ]
Downstream synthetic route of [ 17827-61-1 ]

[ 17827-61-1 ] Synthesis Path-Upstream 1~6

1
[ 922-67-8 ]
[ 158615-33-9 ]
[ 33001-47-7 ]
[ 15366-34-4 ]
[ 17827-61-1 ]

Reference： [1] Canadian Journal of Chemistry, 1994, vol. 72, # 12, p. 2458 - 2467

2
[ 17827-61-1 ]
[ 89179-62-4 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 1209 - 1216
[2] Patent: WO2014/139150, 2014, A1, . Location in patent: Page/Page column 65; 66
[3] Patent: WO2014/150114, 2014, A1, . Location in patent: Page/Page column 66
[4] Patent: WO2015/22073, 2015, A1,

3
[ 17827-61-1 ]
[ 25016-20-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With lithium hydrochloride monohydrate In tetrahydrofuran; methanol; water at 0 - 30℃; for 3 h;	Step 2: To a solution of step 1 intermediate (7.0 g, 50 mmol) in a mixture of THF (20 mL) and MeOH (20 mL) was added a solution of LiOH H₂0 (4.2 g, 100 mmol) in water (20 mL) at 0°C. The RM was stirred at rt for 3 h. The RM was concentrated and subsequently diluted with water. The aqueous layer was acidified with sat. NaHS0₄ solution up to pH~4-5 and extracted with EtOAc. The combined organic layers were dried and concentrated under reduced pressure to yield the desired product (6.2 g, 98percent). LC-MS (Method 3): m/z [M+H]⁺ = 127.2 (MW calc. 126.11); R, = 0.44 min.

Reference： [1] Patent: WO2015/22073, 2015, A1, . Location in patent: Page/Page column 90; 91
[2] Journal of Antibiotics, 1995, vol. 48, # 11, p. 1336 - 1344

4
[ 17827-61-1 ]
[ 79080-39-0 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 1209 - 1216

5
[ 17827-61-1 ]
[ 75092-25-0 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1980, vol. 29, # 5, p. 778 - 784[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1980, # 5, p. 1071 - 1077

6
[ 17827-61-1 ]
[ 84547-62-6 ]

Yield	Reaction Conditions	Operation in experiment
35%	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 18 h;	To a solution of methyl l-methyl-lH-pyrazole-3-carboxylate (22.0g, 157.14 mmol) in tetrahydrofuran (150 mL) was added lithium aluminum hydride (11.9 g, 314.29 mmol) in portions at 0-5°C. Then the reaction was stirred for 18 h at room temperature. The reaction mixture was cooled to 0°C with a water/ice bath, quenched by the addition of 15 mL of water. The resulting solution was diluted with 200 mL of DCM and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated in vacuo to afford (1-methyl- lH-pyrazol-3-yl)methanol as light yellow liquid (6 .0 g ,35percent).

Reference： [1] Patent: WO2014/66795, 2014, A1, . Location in patent: Paragraph 0175
[2] Journal of the Chemical Society, Chemical Communications, 1985, # 24, p. 1765 - 1766

[ 17827-61-1 ] Synthesis Path-Downstream 1~77

1
[ 17827-61-1 ]
[ 89179-62-4 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; at 20℃; for 2h;	A solution of methyl 1-methyl-1H-pyrazole-3-carboxylate (1.1 g, 7.9 mmol) in NH3H20 (10mL) was stirred for 2 h at room temperature. The solvent was evaporated to give the crudeproduct which was used for the next step without further purification.
	With ammonium hydroxide; at 20℃; for 2h;	Step B: 1 -Methyl- lH-pyrazole-3-carboxamide (3)A solution of methyl l-methyl-lH-pyrazole-3-carboxylate (1.1 g, 7.9 mmol) in NuEta32Omicron (10 mL) was stirred for 2 h at room temperature. The solvent was evaporated to give the crude product which was used for the next step without further purification.

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1985,p. 1209 - 1216
[2]Patent: WO2014/139150,2014,A1 .Location in patent: Page/Page column 65; 66
[3]Patent: WO2014/150114,2014,A1 .Location in patent: Page/Page column 66
[4]Patent: WO2015/22073,2015,A1

2
[ 17827-61-1 ]
[ 84547-62-6 ]

Yield	Reaction Conditions	Operation in experiment
35%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 18h;	To a solution of methyl l-methyl-lH-pyrazole-3-carboxylate (22.0g, 157.14 mmol) in tetrahydrofuran (150 mL) was added lithium aluminum hydride (11.9 g, 314.29 mmol) in portions at 0-5C. Then the reaction was stirred for 18 h at room temperature. The reaction mixture was cooled to 0C with a water/ice bath, quenched by the addition of 15 mL of water. The resulting solution was diluted with 200 mL of DCM and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated in vacuo to afford (1-methyl- lH-pyrazol-3-yl)methanol as light yellow liquid (6 .0 g ,35%).

Reference： [1]Patent: WO2014/66795,2014,A1 .Location in patent: Paragraph 0175
[2]Journal of the Chemical Society. Chemical communications,1985,p. 1765 - 1766

3
[ 67-56-1 ]
[ 25016-20-0 ]
[ 17827-61-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; for 2h;Reflux;	To a solution of compound 1 (1.26 g, 10 mmol) in methanol (30 mL) was added sulfuric acid(0.5 mL). The resulting mixture was refluxed for 2h and the solvent was evaporated. The residuewas dissolved in EA (60 mL) and washed with brine, dried over Na2S04. Then filtered andconcentrated to give the product.
	With sulfuric acid; for 2h;Reflux;	Step A: Methyl l-methyl- lH-pyrazole-3-carboxylate (2)To a solution of compound 1 (1.26 g, 10 mmol) in methanol (30 mL) was added sulfuric acid (0.5 mL). The resulting mixture was refluxed for 2h and the solvent was evaporated. The residue was dissolved in EA (60 mL) and washed with brine, dried over Na2S04. Then filtered and concentrated to give the product.
	With thionyl chloride; In ethyl acetate; at 0 - 20℃;	Step 1: Preparation of methyl 1-methyl-1H-pyrazole-3-carboxylate To a solution of <strong>[25016-20-0]1-methyl-1H-pyrazole-3-carboxylic acid</strong> (504 mg, 4 mmol) in MeOH (5 mL) was added SOCl2 (1.4 mL, 20 mmol) at 0 C. The mixture was stirred at r.t overnight then concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with satd. aq. NaHCO3 and concentrated to afford methyl 1-methyl-1H-pyrazole-3-carboxylate. LC-MS: m/z 141 (M+H)+.

With thionyl chloride; at 0 - 20℃;

Step 1: Preparation ofmethyl 1-methyl-JH-pyrazole-3-carboxylate. To a solution of i-methyl1H-pyrazole-3-carboxylic acid (504 mg, 4 mmol) in MeOH (5 mL) was added SOC12 (1.4 mL, 20 mmol) at 0C. The mixture was stirred at r.t overnight then concentrated under reduced pressure. The residue was dissolved in EtOAc, washed withsatd. aq. NaHCO3and concentrated to afford methyl 1 -methyl-1H-pyrazole-3-carboxylate.LC-MS: m/z 141 (M+H).

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1980,vol. 29,p. 778 - 784
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1980,p. 1071 - 1077
[2]Russian Journal of General Chemistry,2011,vol. 81,p. 1745 - 1746
[3]Patent: WO2014/139150,2014,A1 .Location in patent: Page/Page column 65; 66
[4]Patent: WO2014/150114,2014,A1 .Location in patent: Page/Page column 65; 66
[5]Patent: US2015/18328,2015,A1 .Location in patent: Paragraph 1288
[6]Patent: WO2015/3640,2015,A1 .Location in patent: Page/Page column 282

4
[ 17827-61-1 ]
[ 75092-25-0 ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1980,vol. 29,p. 778 - 784
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1980,p. 1071 - 1077

5
[ 186581-53-3 ]
[ 15366-34-4 ]
[ 17827-61-1 ]

Reference： [1]Canadian Journal of Chemistry,1994,vol. 72,p. 2458 - 2467

6
[ 922-67-8 ]
[ 158615-33-9 ]
[ 33001-47-7 ]
[ 15366-34-4 ]
[ 17827-61-1 ]

Reference： [1]Canadian Journal of Chemistry,1994,vol. 72,p. 2458 - 2467

7
[ 17827-61-1 ]
[ 25016-20-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With lithium hydrochloride monohydrate; In tetrahydrofuran; methanol; water; at 0 - 30℃; for 3h;	Step 2: To a solution of step 1 intermediate (7.0 g, 50 mmol) in a mixture of THF (20 mL) and MeOH (20 mL) was added a solution of LiOH H20 (4.2 g, 100 mmol) in water (20 mL) at 0C. The RM was stirred at rt for 3 h. The RM was concentrated and subsequently diluted with water. The aqueous layer was acidified with sat. NaHS04 solution up to pH~4-5 and extracted with EtOAc. The combined organic layers were dried and concentrated under reduced pressure to yield the desired product (6.2 g, 98%). LC-MS (Method 3): m/z [M+H]+ = 127.2 (MW calc. 126.11); R, = 0.44 min.

Reference： [1]Patent: WO2015/22073,2015,A1 .Location in patent: Page/Page column 90; 91
[2]Journal of Antibiotics,1995,vol. 48,p. 1336 - 1344

8
Potassium; 1-methyl-1H-pyrazole-3-carboxylate [ No CAS ]
[ 74-88-4 ]
[ 17827-61-1 ]

Reference： [1]Journal of Antibiotics,1995,vol. 48,p. 1336 - 1344

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In acetonitrile; at 20℃;Cooling with ice;	General procedure: To a mixture of 1H-pyrrole-3-carboxylic acid (1.0 g, 9.00 mmol) and cesium carbonate (1.58 mL, 19.80 mmol) in ACN (20 mL) colled in an ice bath, was added iodomethane (1.68 mL, 27.0 mmol). The resulting mixture was stirred at RT. The mixture was then filtered, and the solid was washed with EtOAc. The filtrate was concentrated and dried under reduced pressure to give methyl 1-methyl-1H-pyrrole-3-carboxylate (577 mg). LCMS- ESI (pos.): 140.1 (M+H)+.

10
[ 694-48-4 ]
[ 17827-61-1 ]

Reference： [1]Journal of Antibiotics,1995,vol. 48,p. 1336 - 1344

11
[ 17827-61-1 ]
3-(bromomethyl)-1-methyl-1H-pyrazole [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1985,p. 1765 - 1766

12
[ 17827-61-1 ]
Tris-(1-methyl-1H-pyrazol-3-ylmethyl)-amine [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1985,p. 1765 - 1766

13
[ 17827-61-1 ]
[ 79080-39-0 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1985,p. 1209 - 1216

14
[ 17827-61-1 ]
3-(chloromethyl)-1-methyl-1H-pyrazole [ No CAS ]

Reference： [1]Patent: WO2014/66795,2014,A1

15
[ 17827-61-1 ]
[ 1142927-97-6 ]

Reference： [1]Patent: WO2014/66795,2014,A1

16
[ 17827-61-1 ]
[ 1607024-25-8 ]

Reference： [1]Patent: WO2014/66795,2014,A1

17
[ 17827-61-1 ]
[ 1607024-26-9 ]

Reference： [1]Patent: WO2014/66795,2014,A1

18
[ 17827-61-1 ]
[ 1607022-82-1 ]

Reference： [1]Patent: WO2014/66795,2014,A1

19
[ 17827-61-1 ]
[ 1607023-04-0 ]

Reference： [1]Patent: WO2014/66795,2014,A1

20
[ 17827-61-1 ]
[ 1607023-34-6 ]

Reference： [1]Patent: WO2014/66795,2014,A1

21
[ 17827-61-1 ]
[ 1607023-49-3 ]

Reference： [1]Patent: WO2014/66795,2014,A1

22
[ 1621-91-6 ]
[ 74-88-4 ]
[ 17827-61-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h;	To a solution of lH-pyrazole-3-carboxylic acid (25.0 g, 223.04 mmol) in DMF (250 mL) was added potassium carbonate (61.6 g, 445.70 mmol) and CH3I (69.7 g, 491.05 mmol) dropwise at 0C and the reaction was stirred for 2 h at room temperature. The resulting mixture was concentrated in vacuo. The residue was dissolved in 150 mL of H20, and the pH was adjusted to 7 with' HC1 (36 %). The resulting solution was extracted with 5x100 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated in vacuo to afford the residue, which was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 :5) to afford methyl 1 -methyl- lH-pyrazole-3-carboxylate as a light yellow solid (22.0 g ,75%).
53%	With caesium carbonate; In acetonitrile; at 16 - 30℃; for 14h;	Step 1 : To a mixture of 1 H-pyrazole-3-carboxylic acid (15.0 g, 134 mmol) and Cs2C03 (109 g, 335 mmol) in CH3CN (250 mL) was added CH3I (29.2 ml, 469 mmol) and the RM was stirred at rt for 14 h. The RM was filtered and filtrate was concentrated under reduced pressure, diluted with EtOAc and washed with water and brine before being dried. The solvent was evaporated under reduced pressure to give the crude product which was purified by CC (Si02; EtOAc/Hex) to yield the desired product (10.0 g, 53%). LC-MS (Method 3): m/z [M+H]+ = 141.3 (MW calc. 140.14); R, = 1.55 min.

Reference： [1]Patent: WO2014/66795,2014,A1 .Location in patent: Paragraph 0175
[2]Patent: WO2015/22073,2015,A1 .Location in patent: Page/Page column 90

23
[ 17827-61-1 ]
[ 304665-45-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 2613 - 2616

24
[ 17827-61-1 ]
C₈H₁₁N₅S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 2613 - 2616

25
[ 17827-61-1 ]
[ 1412407-33-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 2613 - 2616

26
[ 15366-34-4 ]
[ 74-88-4 ]
[ 17827-61-1 ]

Yield	Reaction Conditions	Operation in experiment
66%	With caesium carbonate; In acetonitrile; at 20℃; for 2h;	A solution of <strong>[15366-34-4]methyl 1H-pyrazole-3-carboxylate</strong> (5 g) in dry acetonitrile was treated with cesium carbonate (32.3 g) and methyl iodide (6.45 g) and the mixture was stirred at rt for 2 h. The suspension was filtered and the volatiles were removed under reduced pressure. The residue was purified by chromatography (SiO2, Cy/EtOAc) to yield the desired product (66% yield). LC-MS (Method 1): m/z [M+H]+=141.2 (MW calc.=140.14); Rt=1.0 min.
66%	With caesium carbonate; In acetonitrile; at 20℃; for 2h;	Intermediate 15a) A solution of methyl 1 /-/-pyrazole-3-carboxylate (5 g) in dry acetonitrile was treated with cesium carbonate (32.3 g) and methyl iodide (6.45 g) and the mixture was stirred at rt for 2 h. The suspension was filtered and the volatiles were removed under reduced pressure. The residue was purified by chromatography (Si02, Cy /EtOAc) to yield the desired product (66% yield). LC-MS (Method 1): mlz [M+H]+ = 141.2 (MW calc. = 140.14); R, = 1.0 min.

Reference： [1]Patent: US2014/194443,2014,A1 .Location in patent: Paragraph 0498-0500
[2]Patent: WO2014/108337,2014,A1 .Location in patent: Page/Page column 64; 65

27
[ 17827-61-1 ]
[ 1616929-90-8 ]

Reference： [1]Patent: US2014/194443,2014,A1
[2]Patent: WO2014/108337,2014,A1

28
[ 17827-61-1 ]
[ 1616929-92-0 ]

Reference： [1]Patent: US2014/194443,2014,A1
[2]Patent: WO2014/108337,2014,A1

29
[ 17827-61-1 ]
[ 1616930-47-2 ]

Reference： [1]Patent: US2014/194443,2014,A1
[2]Patent: WO2014/108337,2014,A1

30
[ 17827-61-1 ]
[ 1616930-48-3 ]

Reference： [1]Patent: US2014/194443,2014,A1
[2]Patent: WO2014/108337,2014,A1

31
[ 17827-61-1 ]
[ 1616930-49-4 ]

Reference： [1]Patent: US2014/194443,2014,A1
[2]Patent: WO2014/108337,2014,A1

32
[ 17827-61-1 ]
[ 1616930-50-7 ]

Reference： [1]Patent: US2014/194443,2014,A1
[2]Patent: WO2014/108337,2014,A1

33
[ 17827-61-1 ]
[ 25015-63-8 ]
[ 1616930-45-0 ]

Yield	Reaction Conditions	Operation in experiment
80%		4,4?-Di-tert-butyl-2,2?-dipyridyl (194 mg) was added to a solution of (1,5-Cyclooctadiene)(methoxy)-iridium(I) dimer (241 mg) and pinacolborane (4.13 g) in pentane (21 mL) and the mixture was stirred for 20 min at rt. Then a solution of intermediate 15a (3.02 g) in pentane (14 mL) and THF (7 mL) was added and the solution was stirred at rt for 3 d. The volatiles were removed under reduced pressure and the residue was purified by chromatography (SiO2, DCM/MeOH) to yield the desired product (80% yield). LC-MS (Method 1): m/z [M (boronic acid)+H]+=185.2 (MW (boronic acid) calc.=183.96); Rt=1.4 min.
80%		Intermediate 15b) 4,4'-Di-fert-butyl-2,2'-dipyridyl (194 mg) was added to a solution of (1 ,5-Cyclooctadiene)(methoxy)- iridium(l) dimer (241 mg) and pinacolborane (4.13 g) in pentane (21 mL) and the mixture was stirred for 20 min at rt. Then a solution of intermediate 15a (3.02 g) in pentane (14 mL) and THF (7 mL) was added and the solution was stirred at rt for 3 d. The volatiles were removed under reduced pressure and the residue was purified by chromatography (Si02, DCM / MeOH) to yield the desired product (80% yield). LC-MS (Method 1): mlz [M (boronic acid)+H]+ = 185.2 (MW (boronic acid) calc. = 183.96); R, = 1.4 min.
		To a solution of Ir(COD)2(OMe)2 (5.00 mg, 7.54 pmol, 0.02 equiv) and 4, 4, 5, 5- tetramethyl-l, 3, 2-dioxaborolane (68.5 mg, 535 pmol, 77.7 pL, 1.50 equiv) in -pentane (0.50 mL) was added 4-/er/-butyl-2-(4-/er/-butyl-2-pyridyl)pyridine (5.00 mg, 18.6 pmol, 0.05 equiv) and the mixture was stirred at 25 C for 20 minutes. To this mixture was added a solution of methyl l-methylpyrazole-3-carboxylate (50.0 mg, 357 pmol, 1.00 equiv) in -pentane (0.50 mL) and THF (0.50 mL) and the mixture was stirred at 25 C for 24 h. The mixture was partitioned between ethyl acetate (10.0 mL) and water (10.0 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated to afford the crude product methyl l-methyl-5-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyrazole-3-carboxylate (50.0 mg, 113 pmol, 31.6% yield, 60.0% purity) as a black oil. 1H NMR (400MHz, CDCl3) d = 7.28 (s, 1H), 4.15 (s, 3H), 3.93 (s, 3H), 1.35 (s, 12H).

Reference： [1]Patent: US2014/194443,2014,A1 .Location in patent: Paragraph 0501-0503
[2]Patent: WO2014/108337,2014,A1 .Location in patent: Page/Page column 65
[3]Patent: WO2019/152419,2019,A1 .Location in patent: Paragraph 0374-0375

34
[ 17827-61-1 ]
[ 612511-81-6 ]

Reference： [1]Patent: WO2014/139150,2014,A1
[2]Patent: WO2014/150114,2014,A1

35
[ 17827-61-1 ]
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((1-methyl-1H-pyrazol-3-yl)methylamino)pyridazin-3(2H)-one [ No CAS ]

Reference： [1]Patent: WO2014/139150,2014,A1
[2]Patent: WO2014/150114,2014,A1

36
N¹,N⁵-bis(4,4-difluorocyclohexyl)-biguanide [ No CAS ]
[ 17827-61-1 ]
N²,N⁴-bis(4,4-difluorocyclohexyl)-6-(1-methyl-1H-pyrazol-3-yl)-1,3,5-triazine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate; In methanol; at 20℃;	Step 2: Preparation of N2,N4-bis(4,4-difluorocyclohexyl)-6-(1-methyl-1H-pyrazol-3-yl)-1,3,5-triazine-2,4-diamine To a solution of N1,N5-bis(4,4-difluoro cyclohexyl)-biguanide (120 mg, 0.36 mmol) and <strong>[17827-61-1]methyl 1-methyl-1H-pyrazole-3-carboxylate</strong> (60 mg, 0.43 mmol) in MeOH (2 mL) was added NaOMe (28 mg, 1.07 mmol). The reaction mixture was stirred at r.t. overnight, then poured into water and extracted with EtOAc. Combined organic layers were dried over anhydrous Na2SO4, and concentrated and purified by standard methods to afford N2,N4-bis(4,4-difluorocyclohexyl)-6-(1-methyl-1H-pyrazol-3-yl)-1,3,5-triazine-2,4-diamine. 1H NMR (400 MHz, CDCl3) delta 7.40 (d, J=2.1 Hz, 1H), 6.92 (s, 1H), 5.75-4.94 (m, 2H), 4.28-3.85 (m, 5H), 2.26-1.54 (m, 16H). LC-MS: m/z 428 (M+H)+.
	With sodium methylate; In methanol; at 20℃;	Step 2: Preparation of N2 ,N?-bis (4,4-dfluorocyclohexyl)-6-(1-methyl-1H-pyrazol-3-yl) -1,3,5- triazine-2,4-diamine. To a solution of N?,N5-bis(4,4-difluorocyclohexyl)-biguanide (120 mg, 0.36 mmol) and <strong>[17827-61-1]methyl 1-methyl-1H-pyrazole-3-carboxylate</strong> (60 mg, 0.43 mmol) in MeOH (2 mL) was added NaOMe (28 mg, 1.07 mmol). The reaction mixture was stirred at r.t. overnight, then poured into water and extracted with EtOAc. Combined organic layers were dried over anhydrous Na2SO4,and concentrated and purified by standard methods to afford N2,N4-bis(4,4- difluorocyclohexyl)-6-(i -methyl-i H-pyrazol-3 -yl)- 1,3,5 -triazine-2,4-diamine. ?H NMR (400 MHz, CDC13) 7.40 (d, J= 2.1 Hz, 111), 6.92 (s, 111), 5.75 -4.94 (m, 211), 4.28 - 3.85 (m, 511), 2.26- 1.54 (m, 1611).LC-MS: m/z 428 (M+H).

Reference： [1]Patent: US2015/18328,2015,A1 .Location in patent: Paragraph 1289; 1290
[2]Patent: WO2015/3640,2015,A1 .Location in patent: Page/Page column 282

37
[ 17827-61-1 ]
[ 1221278-28-9 ]

Reference： [1]Patent: WO2015/22073,2015,A1

38
[ 17827-61-1 ]
C₈H₉N₃OS [ No CAS ]

Reference： [1]Patent: WO2015/22073,2015,A1

39
[ 17827-61-1 ]
C₉H₈F₃N₃O₃S₂ [ No CAS ]

Reference： [1]Patent: WO2015/22073,2015,A1

40
[ 17827-61-1 ]
C₂₆H₂₇F₂N₅O₂S [ No CAS ]

Reference： [1]Patent: WO2015/22073,2015,A1

41
[ 17827-61-1 ]
4-[2-(2,6-difluorophenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-5-yl]-5-methyl-2-(1-methyl-1 H-pyrazol-3-yl)thiazole [ No CAS ]

Reference： [1]Patent: WO2015/22073,2015,A1

42
[ 17827-61-1 ]
[ 3430-22-6 ]
C₁₂H₁₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With potassium acetate; palladium diacetate; In N,N-dimethyl acetamide; at 160℃; for 7h;Inert atmosphere;	Step 1: A suspension of methyl 1-methyl-i H-pyrazole-3-carboxylate (2.1 g, 15 mmol), 3-bromo-4-methyl- pyridine (3.08 g, 18 mmol) and KOAc (2.95 g, 30 mmol) in dry DMA (40 ml) was purged with inert gas. Then, Pd(OAc)2 (336 mg, 1.5 mmol) was added. The RM was stirred for 7 h at 160C. The volatiles were removed under reduced pressure, the residue was dissolved in water and extracted with EtOAc. Thecombined organic layers were dried and the volatiles were removed under reduced pressure. The residue was purified by CC (SiC2, MeOH/ CH2CI2) to give the desired compound (964 mg, 28%).1H-NMR (CDCI3): 6 = 2.20 (5, 3H); 3.75 (s, 3H); 3.95 (5, 3H); 6,82 (5, IH); 7.27 (d, J = 5 Hz, 1H); 8.44 (5, 1H); 8.57 (d, J = 5 Hz, 1H). 13C-NMR (CDCI3): 6 = 19.4; 37.6, 52.1; 110.3; 125.3; 125.9; 140.4; 142.7;146.9; 150.3; 150.5; 162.6.

Reference： [1]Patent: WO2015/197188,2015,A1 .Location in patent: Page/Page column 33

43
[ 17827-61-1 ]
[ 3430-22-6 ]
C₁₂H₁₂ClN₃O₂ [ No CAS ]

Reference： [1]Patent: WO2015/197188,2015,A1

44
[ 17827-61-1 ]
(S)-6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-4-((3-fluoropyridin-2-yl)(tetrahydro-2H-pyran-4-yl)methyl)-1-methyl-1,4-dihydropyrazolo[3’,4’:4,5]pyrrolo[3,2-b]pyridine-3-carboxylic acid [ No CAS ]