637336-53-9|Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate| Ambeed

Structure of 637336-53-9

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Quality Control of [ 637336-53-9 ] Purity: 95% SDS Specification

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Product Details of [ 637336-53-9 ]

CAS No. :	637336-53-9
Formula :	C₆H₉N₃O₂
M.W :	155.15
SMILES Code :	O=C(C1=NN(C)C=C1N)OC
MDL No. :	MFCD04969986
InChI Key :	UBOGPSNFKMAOPP-UHFFFAOYSA-N
Pubchem ID :	7017722

Safety of [ 637336-53-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 637336-53-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	5
Fraction Csp3	0.33
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	39.17
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	70.14 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.24
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.29
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.2
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-0.58
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.53
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.04

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.19
Solubility	10.0 mg/ml ; 0.0647 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.33
Solubility	7.34 mg/ml ; 0.0473 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.5
Solubility	49.1 mg/ml ; 0.316 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.04 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.89

Application In Synthesis of [ 637336-53-9 ]

* 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.

Downstream synthetic route of [ 637336-53-9 ]

[ 637336-53-9 ] Synthesis Path-Downstream 1~35

1
[ 637336-53-9 ]
[ 76-83-5 ]
[ 637336-55-1 ]

Yield	Reaction Conditions	Operation in experiment
91.1%	With triethylamine; In aqueous hydrochloric acid; dichloromethane; N,N-dimethyl-formamide;	Step 4 Preparation of 1-methyl-4-(trityl-amino)-1H-pyrazole-3-carboxylic acid methyl ester A solution of <strong>[637336-53-9]4-amino-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester</strong> (160 mg, 1.03 mmol) in N,N-dimethylformamide (1.0 mL) at 25 C. was treated with triethylamine (0.35 mL, 2.6 mmol) and triphenylmethylchloride (316 mg, 1.13 mmol). Additional N,N-dimethylformamide (2.0 mL) was added to the reaction to aid stirring. The reaction was stirred at 25 C. for 18 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in dichloromethane (50 mL) and then was washed with a IN aqueous hydrochloric acid solution (110 mL), a saturated aqueous sodium bicarbonate solution (110 mL), and a saturated aqueous sodium chloride solution (1*10 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 1-methyl-4-(trityl-amino)-1H-pyrazole-3-carboxylic acid methyl ester (373 mg, 91.1%) as an off-white solid: 1H NMR (DMSO-d6, 300 MHz) delta7.25 (m, 16H), 3.74 (s, 3H), 3.53 (s, 3H).
91.1%	With triethylamine; In DMF (N,N-dimethyl-formamide); at 25℃; for 18h;	(160 mg, 1.03 mmol) [IN N, N DIMETHYLFORMAMIDE] (1.0 mL) at [25 oC] was treated with triethylamine (0.35 mL, 2.6 mmol) and triphenylmethylchloride (316 mg, 1.13 mmol). Additional [N, N DIMETHYLFORMAMIDE] (2.0 mL) was added to the reaction to aid stirring. The reaction was stirred at [25 oC] for 18 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in dichloromethane (50 mL) and then was washed with a 1N aqueous hydrochloric acid solution [(1 X 10] mL), a saturated aqueous sodium bicarbonate solution [(1 X 10] mL), and a saturated aqueous sodium chloride solution [(1 X 10] mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford [1-METHYL-4- (TRITYL-AMINO)-LH-PYRAZOLE-3-CARBOXYLIC] acid methyl ester (373 mg, 91.1%) as an off-white solid

References: [1]Patent: US2004/14766,2004,A1 .
[2]Patent: WO2003/106459,2003,A1 .Location in patent: Page 163.

2
[ 400877-57-8 ]
[ 637336-53-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 4h;	10% palladium/C (2.87 g, 2.7 mmol) was added to a stirred solution of methyl 1 -methyl- 4-nitro-1 H-pyrazole-3-carboxylate (p69, 7.15 g, 38.6 mmol) in methanol (250 ml_) and stirred at RT under H2 atmosphere for 4 hrs. The catalyst was filtered off and the solvent was evaporated under vacuum to afford methyl 4-amino-1 -methyl-1 H-pyrazole- 3-carboxylate (p70, 6 g, y= quant) as purple wax used as such in the next step. MS (/T7/z): 156.1 [MH]+
100%	With palladium on activated charcoal; hydrogen; In methanol; at 20℃; under 775.743 Torr; for 12h;Inert atmosphere;	To a solution of methyl 1-methyl-4-nitro-pyrazole-3-carboxylate (2 g, 10.8 mmol, CAS400877-57-8) in MeOH (20 mL) was added Pd/C (200 mg, 10% wt) under N2 atmosphere. The suspension was degassed and purged with H2 gas 3 times. The mixture was stirred under H2 (15 Psi) at rt for 12 hr. On completion, the reaction mixture was filtered and concentrated in vacuo to give the title compound (1.68 g, 100% yield) as a white solid. 1H NMR (400 MHz, CDCl3) delta 6.95 (s, 1H), 3.92 (s, 3H), 3.86 (s, 3H).
96%	palladium; In methanol;	Step 3 Preparation of 4-amino-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester A mixture of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid methyl ester (500 mg, 2.7 mmol) and 10% palladium on carbon (50 mg) in methanol (25 mL) was subjected to 60 psi pressure of hydrogen gas in a Parr apparatus for 24 h. At this time, the reaction mixture was filtered through a pad of celite and washed with methanol. The filtrate was concentrated in vacuo to afford 4-amino-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester (402 mg, 96%) as an off-white solid: 1H NMR (DMSO-d6, 300 MHz) delta7.10 (s, 1H), 4.65 (broad s, 2H), 3.73 (s, 3H), 3.72 (s, 3H).

96%	With hydrogen;palladium 10% on activated carbon; In methanol; under 3102.97 Torr; for 24h;	A mixture of [1-METHYL-4-NITRO-LH-PYRAZOLE-3-CARBOXYLIC] acid methyl ester (500 mg, 2.7 mmol) and 10% palladium on carbon [(50] mg) in methanol [(25] mL) was subjected to 60 psi pressure of hydrogen gas in a Parr apparatus for 24 h. At this time, the reaction mixture was filtered through a pad of celite and washed with methanol. The filtrate was concentrated in vacuo to afford [4-AMINO-1-METHYL-LH-PYRAZOLE-3-] carboxylic acid methyl ester (402 mg, 96%) as an off-white solid
95%	With hydrogen;palladium 10% on activated carbon; In methanol; under 30402.0 Torr;	240 mg (1.30 mM) of the compound obtained in Preparative Example 7 was dissolved in 5 ml of methanol, to which 24 mg of 10% palladium/charcoal was added dropwise, and the resulting mixture was stirred under hydrogen pressure of 40 atm for 30 minutes. After the reaction was terminated, the resulting reaction solution was filtered through cellite, and distilled under reduced pressure, to obtain 191 mg (95%) of the title compound.1H NMR (300 MHz, CDCl3) delta 3.86 (s, 3H), 3.92 (s, 3H), 6.91 (s, 1H).Mass: 155 (M+)
95%	With palladium on activated charcoal; In methanol; at 25℃; for 1h;	A solution of methyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate (1.0 g, 5.41 mmol) and Pd/C (200 mg) in MeOH (60 mL) was stirred for 1 hour at 25C. Pd/C was filtered out and the filtrate was concentrated to give desired compound as a white solid (800 mg, 95%).
95%	With hydrogen;palladium 10% on activated carbon; In methanol; under 30402.0 Torr; for 0.5h;	240 mg (1.30 mM) of the compound obtained in Preparative Example 7 was dissolved in 5 ml of methanol, to which 24 mg of 10% palladium/ EPO <DP n="28"/>charcoal was added dropwise, and the resulting mixture was stirred under hydrogen pressure of 40 atm for 30 minutes. After the reaction was terminated, the resulting reaction solution was filtered through cellite, and distilled under reduced pressure, to obtain 191 mg (95%) of the title compound.1H NMR(SOOMHZ, CDCl3) delta 3.86(s, 3H), 3.92(s, 3H), 6.91(s, IH). Mass : 155(M+)
84%	With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃;Inert atmosphere;	A solution of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid methyl ester (4.8 g, 25.94 mmol) in dry MeOH (100 ml) was thoroughly purged with argon, treated with 10% Pd-C (2.7 g, 2.59 mmol), and again purged with argon. Then the reaction mixture was hydrogenated under a balloon pressure of hydrogen at rt for overnight. The reaction mixture was filtered through a bed of celite. The filtrate was concentrated and dried to give the title compound as gray - whitesolid (3.4 g, 84%), which was used in the next reaction step without further purification.
84%	With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃;Inert atmosphere;	A solution of l-methyl-4-nitro-lH-pyrazole-3-carboxylic acid methyl ester (4.8 g, 25.94 mmol) in dry MeOH (100ml) was thoroughly purged with argon, treated with 10% Pd-C (2.7 g, 2.59 mmol), and again purged with argon. Then the reaction mixture was hydrogenated under a balloon pressure of hydrogen at rt for overnight. The reaction mixture was filtered through a bed of celite. The filtrate was concentrated and dried to give the title compound as gray-white solid (3.4 g, 84%), which was used in the next reaction step without further purification.
	With palladium 10% on activated carbon; hydrogen; In methanol; under 2068.65 Torr; for 1h;	Methyl-4-nitro-lH-pyrazole-3-carboxylate (5.0 g, 27.01 mmol)Added to a hydrogenation reaction flask containing 50mL of methanol,Pd / C (10%, 0.5 g) was added,40psi hydrogen pressure reaction 1.0h,TLC test showed that the reaction was completed,Suction filtration, Pd / C filtration, and concentrated under reduced pressure to give the crude product (3.72 g, 88.7%),The crude product was used without purification in the next reaction administered.
8.57 g	With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; under 2327.23 Torr; for 6h;	B) Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate To a solution of methyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate (10 g) in methanol (200 mL), palladium-carbon (10%) (2 g) was added, and the mixture was stirred at room temperature for 6 hours in a hydrogen atmosphere (45 psi). Palladium-carbon was filtered off, and then, the filtrate was concentrated to obtain the title compound (8.57 g). 1H NMR (400 MHz, CDCl3) delta 3.86 (3H, s), 3.92 (3H, s), 4.08 (2H, brs), 6.96 (1H, s).
	With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 4h;	10% palladium/C (2.87 g, 2.7 mmol) was added to a stirred solution of methyl 1-methyl- 4-nitro-1 H-pyrazole-3-carboxylate (p129, 7.15 g, 38.6 mmol) in methanol (250 ml_) and stirred at RT under H2 atmosphere for 4 hrs. The catalyst was filtered off and the solvent was evaporated under vacuum to afford methyl 4-amino-1-methyl-1 H-pyrazole- 3-carboxylate (p130, 6 g, y= quant) as purple wax used as such in the next step. MS (/T7/z): 156.1 [MH]+.

References: [1]Patent: WO2019/81939,2019,A1 .Location in patent: Page/Page column 78.
[2]Patent: US2019/192668,2019,A1 .Location in patent: Paragraph 3146; 3147.
[3]Patent: US2004/14766,2004,A1 .
[4]Patent: WO2003/106459,2003,A1 .Location in patent: Page 162.
[5]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 979 - 984.
[6]Patent: US2010/63106,2010,A1 .Location in patent: Page/Page column 11.
[7]Patent: WO2017/15449,2017,A1 .Location in patent: Page/Page column 157.
[8]Patent: WO2008/51047,2008,A1 .Location in patent: Page/Page column 25-26.
[9]Patent: US2011/306589,2011,A1 .Location in patent: Page/Page column 53.
[10]Patent: WO2011/154327,2011,A1 .Location in patent: Page/Page column 137.
[11]Tetrahedron Letters,2009,vol. 50,p. 2624 - 2627.
[12]Patent: CN107235906,2017,A .Location in patent: Paragraph 0130-0133.
[13]Patent: EP3287441,2018,A1 .Location in patent: Paragraph 0294.
[14]Patent: WO2019/43407,2019,A1 .Location in patent: Page/Page column 127.

4
[ 637336-53-9 ]
[ 598-21-0 ]
[ 1021498-10-1 ]

Yield	Reaction Conditions	Operation in experiment
69%	With triethylamine; In tetrahydrofuran;Inert atmosphere;	Preparative Example 9 4-(2-bromoacetylamino)-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester 160 mg (1.03 mM) of the compound obtained in Preparative Example 8 was dissolved in 3 ml of tetrahydrofuran, to which 0.11 ml (1.24 mM) of bromo acetylbromide and 0.22 ml (1.55 mM) of triethylamine were added dropwise, and the resulting mixture was stirred under a nitrogen atmosphere for a day. The solvent was distilled off under reduced pressure, and the resultant was extracted with ethyl acetate and brine. The organic solvent layer was dried over anhydrous sodium sulfate, filtered, and then distilled under reduced pressure. The resulting impure compound was purified by column chromatography (hexane:ethyl acetate=1:1), to obtain 100 mg (69%) of the title compound. 1H NMR (300 MHz, CDCl3) delta 3.79 (s, 3H), 3.99 (s, 3H), 4.03 (s, 2H), 8.20 (s, 1H), 9.95 (br, NH). Mass: 275 (Br79+), 277 (Br81)
69%	With triethylamine; In tetrahydrofuran; for 24h;	160 mg (1.03 mM) of the compound obtained in Preparative Example 8 was dissolved in 3 ml of tetrahydrofuran, to which 0.11 ml (1.24 mM) of bromo acetylbromide and 0.22 ml (1.55 mM) of triethylamine were added dropwise, and the resulting mixture was stirred under a nitrogen atmosphere for a day. The solvent was distilled off under reduced pressure, and the resultant was extracted with ethyl acetate and brine. The organic solvent layer was dried over anhydrous sodium sulfate, filtered, and then distilled under reduced pressure. The resulting impure compound was purified by column chromatography (hexane : ethyl acetate = 1 : 1), to obtain 100 mg(69%) of the title compound.1H NMR(300MHz, CDCl3) delta 3.79(s, 3H), 3.99(s, 3H), 4.03(s, 2H), 8.20(s, IH), 9.95(br, NH).Mass : 275(Br79+), 277(Br81)

References: [1]Patent: US2010/63106,2010,A1 .Location in patent: Page/Page column 11.
[2]Patent: WO2008/51047,2008,A1 .Location in patent: Page/Page column 26.

5
[ 138786-86-4 ]
[ 637336-53-9 ]

References: [1]Patent: US2011/306589,2011,A1 .
[2]Patent: WO2003/106459,2003,A1 .
[3]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 979 - 984.
[4]Patent: CN107235906,2017,A .
[5]Patent: WO2011/154327,2011,A1 .
[6]Patent: WO2008/51047,2008,A1 .

6
[ 637336-53-9 ]
[ 1352200-22-6 ]

References: [1]Patent: US2011/306589,2011,A1 .
[2]Patent: WO2011/154327,2011,A1 .

7
[ 637336-53-9 ]
[ 1352195-40-4 ]

References: [1]Patent: US2011/306589,2011,A1 .
[2]Patent: WO2011/154327,2011,A1 .

8
[ 637336-53-9 ]
[ 1316122-15-2 ]
[ 1352200-21-5 ]

Yield	Reaction Conditions	Operation in experiment
69%		To a stirred solution of A-2 (600 mg, 2.34 mmol) in DMF (10 ml) was added EDCI (672 mg, 3.51 mmol) and HOBt (538 mg, 3.51 mmol) at 25 C. Stirring was continued for 10 min. 4-Amino-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester (362 mg, 2.35 mmol) and triethylamine (0.8 ml, 5.35 mmol) were subsequently added to the above solution. The reaction mixture was stirred at 25 C. overnight, then quenched with water (8 ml), and extracted with CH2Cl2. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and evaporated. The crude product thus obtained was purified by column chromatography over silica gel (2% MeOH /CH2Cl2) to provide the title compound (642 mg, 69%) as yellow sticky solid.
69%		To a stirred solution of A-2 (600 mg, 2.34 mmol) in DMF (10ml) was added EDCI (672 mg, 3.51 mmol) and HOBt (538 mg, 3.51 mmol) at 25C. Stirring was continued for 10 min. 4- Amino-l-methyl-lH-pyrazole-3-carboxylic acid methyl ester (362 mg, 2.35 mmol) and triethylamine (0.8 ml, 5.35 mmol) were subsequently added to the above solution. The reaction mixture was stirred at 25C overnight, then quenched with water (8 ml), and extracted with CH2C12. The combined organic layers were washed with brine, dried (Na2S04), filtered, and evaporated. The crude product thus obtained was purified by column chromatography over silica gel (2% MeOH/CH2Cl2) to provide the title compound (642 mg, 69%) as yellow sticky solid.

References: [1]Patent: US2011/306589,2011,A1 .Location in patent: Page/Page column 53.
[2]Patent: WO2011/154327,2011,A1 .Location in patent: Page/Page column 137.

9
[ 637336-53-9 ]
[ 1352194-72-9 ]

References: [1]Patent: WO2011/154327,2011,A1 .

10
[ 637336-53-9 ]
[ 637336-52-8 ]

References: [1]Patent: WO2003/106459,2003,A1 .

11
[ 637336-53-9 ]
[ 637336-56-2 ]

References: [1]Patent: WO2003/106459,2003,A1 .

12
[ 637336-53-9 ]
(4-bromo-1-methyl-1H-pyrazol-3-yl)-(3-hydroxy-3-trifluoromethyl-3,3a,4,5,6,7-hexahydroindazol-2-yl)methanone [ No CAS ]