[ CAS No. 5203-77-0 ] {[proInfo.proName]}

Name: 5203-77-0|1,3-Dimethyl-1H-pyrazol-5-ol|97%
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SKU: A343755
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Quality Control of [ 5203-77-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 5203-77-0 ]

Product Details of [ 5203-77-0 ]

CAS No. :	5203-77-0	MDL No. :	MFCD00129673
Formula :	C₅H₈N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JXPVQFCUIAKFLT-UHFFFAOYSA-N
M.W :	112.13	Pubchem ID :	2766847
Synonyms :

Calculated chemistry of [ 5203-77-0 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.4
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	30.48
TPSA :	38.05 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) :	-6.55 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.15
Log Po/w (XLOGP3) :	0.61
Log Po/w (WLOGP) :	0.43
Log Po/w (MLOGP) :	0.14
Log Po/w (SILICOS-IT) :	0.32
Consensus Log Po/w :	0.53

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.38
Solubility :	4.65 mg/ml ; 0.0415 mol/l
Class :	Very soluble
Log S (Ali) :	-0.98
Solubility :	11.7 mg/ml ; 0.104 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.55
Solubility :	31.7 mg/ml ; 0.282 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.55

Safety of [ 5203-77-0 ]

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 [ 5203-77-0 ]

* 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 [ 5203-77-0 ]
Downstream synthetic route of [ 5203-77-0 ]

[ 5203-77-0 ] Synthesis Path-Upstream 1~4

1
[ 141-97-9 ]
[ 60-34-4 ]
[ 5203-77-0 ]

Yield	Reaction Conditions	Operation in experiment
74%	at 20℃; for 0.0833333 h;	3.16 1-Methyl-1H-pyrazol-5-ol (25a) A solution of methylhydrazine (2b) (0.57 mL, 10.9 mmol) in PhMe (2 mL) was added dropwise to a solution of ethyl acetoacetate (24) (1.39 mL, 10.9 mmol) in PhMe (3 mL). The mixture was stirred at room temperature for 5 min and then evaporated in vacuo. Purification by recrystallization (MeOH/EtOAc) gave the title compound (0.90 g, 74percent) as a pale yellow solid, mp 112-115 °C (lit. ⁴⁸ mp 112.5-113.5 °C) (found: 113.0709. C₅H₉N₂O [MH] requires 113.0709); FTIR (KBr)/cm^-1 ν_max 1549, 1269, 1185, 1034; ¹H NMR (400 MHz; CDCl₃) δ 3.21 (3H, s, Me), 3.11 (2H, s, CH₂), 2.02 (3H, s, 3-Me); ¹³C NMR (100 MHz, CDCl₃) δ 172.2 (C), 155.5 (C), 41.4 (CH₂), 31.0 (Me), 16.9 (Me); LRMS (APcI) m/z (rel intensity) 113 (MH⁺, 100).
61%	at 80℃; for 5 h; Reflux	General procedure: A solution of ethyl acetoacetate or benzoylacetate (0.01 mol) in 20 mL ethanol was added to the methylhydrazine (0.02 mol) dropwise under the ice bath. Then the mixture was refluxed at 80 °C for 5 h. After cooling, filtered and dried the precipitate. The solid obtained was pure and did not need recrystallization. The compound 2a obtained gave the yield of 61percent, and the melting point of 2a was determined as 211-212 °C, which was reported as 213 °C in the reference [13]. The compound 2b obtained gave the yield of 67 percent, and the melting point of 2b was determined as 117-118 °C (116-117 °C was reported in the reference [17]).

Reference： [1] Tetrahedron, 2013, vol. 69, # 39, p. 8429 - 8438
[2] Letters in Drug Design and Discovery, 2016, vol. 13, # 8, p. 800 - 808
[3] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 10, p. 2590 - 2594

2
[ 105-45-3 ]
[ 60-34-4 ]
[ 5203-77-0 ]

Yield	Reaction Conditions	Operation in experiment
66 g	at 20 - 40℃;	To a mixture of methyl acetoacetate (70 g, 0.6 mol) in ethanol (500 ml) in a round bottom flask was added drop wise methyl hydrazine (27.6 g, 0.6 mol) with an ice-water bath to keep the temperature below 40° C. The resulting mixture was then stirred at RT for overnight. The solvent was then removed under rotary evaporator to dryness, the solid product was further dried under vacuum, an off-white solid product B (66 grams) was obtained, and used without further purification in next dye formation step.

Reference： [1] Patent: US2016/333210, 2016, A1, . Location in patent: Paragraph 0055; 0058

3
[ 4341-76-8 ]
[ 60-34-4 ]
[ 5203-77-0 ]

Reference： [1] Journal of Fluorine Chemistry, 1990, vol. 48, # 1, p. 123 - 131

4
[ 5203-77-0 ]
[ 68-12-2 ]
[ 27006-76-4 ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: at 20℃; for 0.333333 h; Stage #2: at 80℃;	General procedure: Phosphorus oxychloride (0.07 mol) was added dropwise to ice cooled N,N-dimethylformamide (0.03 mol) and then stirred for 20 min at room temperature. Compound 2a or 2b (0.02 mol) was added to the mixture and reacted for 1-5 h at 80 °C. After cooling, poured the reaction mixture was poured into 50 ml ice/water mixture, ensuring the mixture temperature to be below 35 °C. Dichloromethane (30 mL x 3) was used to extract the aqueous layer. Then anhydrous MgSO₄ was used to dry the combined layer of dichloromethane. A yellow solid 3a or 3b was obtained after the evaporation of the solvent under 35 °C. The compound 3a obtained gave the yield of 56 percent, and the melting point of 3a was determined as 76-77 °C (The melting point in the reference [18] was 78-79 °C). The compound 3b obtained gave the yield of 52percent, and the melting point of 3b was determined as 61-62 °C (63 °C was reported in the reference [18]).

Reference： [1] Letters in Drug Design and Discovery, 2016, vol. 13, # 8, p. 800 - 808

[ 5203-77-0 ] Synthesis Path-Downstream 1~88

1
[ 4894-61-5 ]
[ 5203-77-0 ]
1,3-dimethyl-4-bis-(2-butenyl)-5-pyrazolone [ No CAS ]

Reference： [1]Heterocycles,1993,vol. 36,p. 1375 - 1380

2
[ 4341-76-8 ]
[ 60-34-4 ]
[ 5203-77-0 ]

Reference： [1]Journal of Fluorine Chemistry,1990,vol. 48,p. 123 - 131

3
[ 141-97-9 ]
[ 60-34-4 ]
[ 5203-77-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	In methanol; at 20℃; for 2.33333h;Reflux;	At room temperature, a solution of methyl hydrazine (4.66 g, 0.101 mol) in methanol (6 ml) was added dropwise to a solution of ethyl acetoacetate (13.0 g, 0.1 mol) in methanol (70 ml). The dropwise addition was carried out for 20 minutes. The temperature of the solution obtained during the dropwise addition was raised to 45 C.The reaction solution was heated to reflux, the dehydrator was dehydrated, and the reaction was refluxed for 2 hours. The TLC plate monitored, and a small amount of raw materials remained.An appropriate amount of solvent was removed under reduced pressure, and ethyl acetate / petroleum ether (1: 2) was added to beat and filtered to obtain 10.6 g of a red solid product. Yield: 93%
74%	In toluene; at 20℃; for 0.0833333h;	3.16 1-Methyl-1H-pyrazol-5-ol (25a) A solution of methylhydrazine (2b) (0.57 mL, 10.9 mmol) in PhMe (2 mL) was added dropwise to a solution of ethyl acetoacetate (24) (1.39 mL, 10.9 mmol) in PhMe (3 mL). The mixture was stirred at room temperature for 5 min and then evaporated in vacuo. Purification by recrystallization (MeOH/EtOAc) gave the title compound (0.90 g, 74%) as a pale yellow solid, mp 112-115 C (lit. 48 mp 112.5-113.5 C) (found: 113.0709. C5H9N2O [MH] requires 113.0709); FTIR (KBr)/cm-1 numax 1549, 1269, 1185, 1034; 1H NMR (400 MHz; CDCl3) delta 3.21 (3H, s, Me), 3.11 (2H, s, CH2), 2.02 (3H, s, 3-Me); 13C NMR (100 MHz, CDCl3) delta 172.2 (C), 155.5 (C), 41.4 (CH2), 31.0 (Me), 16.9 (Me); LRMS (APcI) m/z (rel intensity) 113 (MH+, 100).
61%	In ethanol; at 80℃; for 5h;Reflux;	General procedure: A solution of ethyl acetoacetate or benzoylacetate (0.01 mol) in 20 mL ethanol was added to the methylhydrazine (0.02 mol) dropwise under the ice bath. Then the mixture was refluxed at 80 C for 5 h. After cooling, filtered and dried the precipitate. The solid obtained was pure and did not need recrystallization. The compound 2a obtained gave the yield of 61%, and the melting point of 2a was determined as 211-212 C, which was reported as 213 C in the reference [13]. The compound 2b obtained gave the yield of 67 %, and the melting point of 2b was determined as 117-118 C (116-117 C was reported in the reference [17]).

Reference： [1]Patent: CN110615781,2019,A .Location in patent: Paragraph 0227; 0229; 0230
[2]New Journal of Chemistry,2019,vol. 43,p. 3000 - 3010
[3]Tetrahedron,2013,vol. 69,p. 8429 - 8438
[4]Letters in drug design and discovery,2016,vol. 13,p. 800 - 808
[5]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2590 - 2594

4
[ 5203-77-0 ]
[ 552-89-6 ]
[ 888229-56-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2590 - 2594

5
[ 5203-77-0 ]
[ 137527-44-7 ]

Reference： [1]Heterocycles,2003,vol. 60,p. 2323 - 2342

6
[ 137640-94-9 ]
[ 5203-77-0 ]
[ 157328-20-6 ]

Yield	Reaction Conditions	Operation in experiment
31%	With potassium hydroxide;copper(l) chloride; In methanol; hexane; ethyl acetate; N,N-dimethyl-formamide; toluene;	EXAMPLE 10 Preparation of N-(4-fluorophenyl)-2-(1',3'-dimethylpyrazol-5'-yloxy)-6-pyridinecarboxamid 2.2 g of 1,3-dimethyl-5-hydroxypyrazol was added to a solution of 1.1 g potassium hydroxide in 40 ml methanol. The solvent was evaporated in vacuo after toluene was added to give the anhydrous potassium salt. The residue was resolved in 15 ml anhydrous N,N-dimethylformamide. After the addition of 5 g N-(4-fluorophenyl)-2-chloro-6-pyridinecarboxamide and 0.2 g CuCl the mixture was heated to reflux for 6 hours. After cooling, the reaction mixture was poured into 200 ml water and 200 ml ethyl acetate. The organic layer was separated and the aqueous phase extracted one more time with ethyl acetate. The combined extracts were dried with anhydrous magnesium sulphate and the solvent was removed in vacuo. The crude product was purified by flash silica gel column chromatography using hexane/ethyl acetate (7/3). The title compound was obtained as a white solid (2 g, 31%), mp 114.

Reference： [1]Patent: US5707932,1998,A

7
2-chloro-4-methylsulfonyl-3-(oxazol-5-yl)-benzoyl chloride [ No CAS ]
[ 1634-04-4 ]
[ 5203-77-0 ]
[ 78-97-7 ]
1,3-dimethyl-4-[2-chloro-4-methylsulfonyl-3-(oxazol-5-yl)-benzoyl]-5-hydroxy-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; potassium carbonate; sodium sulfate; triethylamine; In ethyl acetate; acetonitrile;	a. 1.22 g (10.9 mmol) of <strong>[5203-77-0]1,3-dimethyl-5-hydroxypyrazole</strong> and 1.1 g (10.9 mmol) of triethylamine are dissolved in 75 ml of acetonitrile and treated at 0 C. with 3.5 g (10.9 mmol) of 2-chloro-4-methylsulfonyl-3-(oxazol-5-yl)-benzoyl chloride in 50 ml of acetonitrile. Stirring is continued at 0 C for 1 hour, and 4.45 g (44 mmol) of triethylamine and 0.61 g (7.2 mmol) of acetocyanohydrin are subsequently added dropwise at room temperature. The solution is stirred at room temperature for 12 hours. For working up, the mixture is first treated with dilute hydrochloric acid and extracted using methyl tert-butyl ether. The ether phase is then extracted using 5% strength potassium carbonate solution. After the aqueous phase has been acidified with hydrochloric acid, the product is extracted from the aqueous phase using ethyl acetate. The ethyl acetate phase is dried using sodium sulfate and concentrated. This gives 1.2 g of crude product which is purified by column chromatography. This gives 0.4 g (27% of theory) of 1,3-dimethyl-4-[2-chloro-4-methylsulfonyl-3-(oxazol-5-yl)-benzoyl]-5-hydroxy-pyrazole, m.p.: 236-241 C. The compound shown in the table which follows is obtained by a similar method:

Reference： [1]Patent: US5846907,1998,A

8
[ 614-68-6 ]
[ 5203-77-0 ]
5-hydroxy-1,3-dimethyl-N-(2-methylphenyl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; triethylamine; In 5,5-dimethyl-1,3-cyclohexadiene; ethanol; water;	Preparative Example 1 5-Hydroxy-1,3-dimethyl-N-(2-methylphenyl)-1H-pyrazole-4-carboxamide A mixture of 22.4 g (0.2 mol) <strong>[5203-77-0]5-hydroxy-1,3-dimethyl-1H-pyrazole</strong> [K. Auwers, J.Prakt.Chem., 110, 153 (1925)], 26.6 g (0.2 mol) o-tolylisocyanate in 150 ml xylene containing 1 ml triethylamine is heated to reflux for 1.5 hours. The reaction mixture is cooled and extracted with 200 ml of a 1 N aqueous sodium hydroxide solution. The aqueous phase is separated, filtered and then acidified with 120 ml of a 1 N solution of hydrochloric acid. The precipitate is collected and washed with water. The crude product is recrystallized from a mixture of 120 ml ethanol and 200 ml water, giving 29.5 g of a nearly white solid of mp. 208-210 C. (with decomposition). Analysis calculated: 63.67% C, 6.16% H, 17.12% N. Found: 63.85% C, 6.33% H, 17.32% N.

Reference： [1]Patent: US4346097,1982,A

9
[ 5203-77-0 ]
[ 216485-62-0 ]
[ 1070778-70-9 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation of 4-[3-amino-2-methyl-4-(methylsulfonyl)benzoyl]-<strong>[5203-77-0]1,3-dimethyl-5-hydroxypyrazole</strong> Under nitrogen, 0.50 g (2.2 mmol) of 3-amino-2-methyl-4-(methylsulfonyl)benzoic acid, 0.32 g (2.8 mmol) of <strong>[5203-77-0]1,3-dimethyl-5-hydroxypyrazole</strong> and 0.50 g (2.6 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dissolved in dry acetonitrile. The mixture was stirred at RT for 1 day and allowed to stand for 2 days. 0.61 ml (4.4 mmol) of NEt3, 0.12 ml (0.9 mmol) of Me3SiCN and a spatula tip of KCN were added, and the mixture was stirred at RT for 2 days. The solvent was removed under reduced pressure, and the residue was taken up in CH2Cl2 and 10% strength H2SO4. The organic phase was separated off and dried over MgSO4, and the solvent was removed under reduced pressure. The residue was crystallized from acetonitrile. The mother liquor was purified by preparative HPLC. This gave 0.10 g in a purity of 97%. 1H-NMR: delta[CDCl3] 1.74 (s, 3H), 2.13 (s, 3H), 3.08 (s, 3H), 3.64 (s, 3H), 5.28 (br, 2H), 6.72 (d, 1H), 7.75 (d, 1H).

Reference： [1]Patent: US2008/254990,2008,A1 .Location in patent: Page/Page column 7

10
[ 1070779-73-5 ]
[ 5203-77-0 ]
[ 1070778-77-6 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2: 1,3-Dimethyl-4-[3-cyclopropylamino-2-methyl-4-(methylsulfonyl)benzoyl]-5-hydroxypyrazole Under nitrogen, 0.50 g (1.9 mmol) of 3-cyclopropylamino-2-methyl-4-(methyl-sulfonyl)benzoic acid, 0.27 g (2.4 mmol) of <strong>[5203-77-0]1,3-dimethyl-5-hydroxypyrazole</strong> and 0.43 g (2.2 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dissolved in dry acetonitrile. The mixture was stirred at RT for 1 day and allowed to stand for 2 days. 0.52 ml (3.7 mmol) of NEt3, 0.10 ml (0.7 mmol) of Me3SiCN and a spatula tip of KCN were added, and the mixture was stirred at RT for 2 days. The solvent was removed under reduced pressure, and the residue was taken up in CH2Cl2 and 10% strength H2SO4. The organic phase was separated off, the aqueous phase was extracted once with CH2Cl2, the combined organic phases were dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC. This gave 0.16 g of a white-beige amorphous solid in a purity of 93%. 1H-NMR: delta[CDCl3] 0.57-0.65 (m, 2H), 0.75-0.83 (m, 2H), 1.75 (s, 3H), 2.43 (s, 3H), 2.80-2.87 (m, 1H), 2.99 (s, 3H), 3.64 (s, 3H), 6.80 (d, 1H), 7.77 (d, 1H)

Reference： [1]Patent: US2008/254990,2008,A1 .Location in patent: Page/Page column 7

11
[ 1070779-72-4 ]
[ 5203-77-0 ]
[ 1070779-36-0 ]

Yield	Reaction Conditions	Operation in experiment
		Under nitrogen, 0.41 g (1.3 mmol) of [3-(2-ethoxyethyl)(methyl)amino]-2-methyl-4-(methylsulfonyl)benzoic acid, 0.19 g (1.7 mmol) of <strong>[5203-77-0]1,3-dimethyl-5-hydroxypyrazole</strong> and 0.30 g (1.6 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dissolved in dry acetonitrile. The mixture was stirred at RT for 1 day and allowed to stand for 2 days. 0.36 ml (2.6 mmol) of NEt3, 0.07 ml (0.5 mmol) of Me3SiCN and a spatula tip of KCN were added, and the mixture was stirred at RT for 2 days. The solvent was removed under reduced pressure, and the residue was taken up in CH2Cl2 and 10% strength H2SO4. The organic phase was separated off and dried over MgSO4, and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC. This gave 0.22 g of a brown oil in a purity of 98%.1H-NMR: delta[CDCl3] 1.19 (t, 3H), 1.68 (s, 3H), 2.32 (s, 3H), 2.94 (s, 3H), 3.19-3.31 (m, 1H), 3.37 (s, 3H), 3.40-3.51 (m, 1H), 3.51 (q, 2H), 3.65 (s, 3H), 3.67-3.73 (m, 2H), 7.21 (d, 1H), 8.05 (d, 1H).

Reference： [1]Patent: US2008/254990,2008,A1 .Location in patent: Page/Page column 7

12
[ 1019321-20-0 ]
[ 5203-77-0 ]
[ 1019321-19-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; at 5 - 20℃; for 6h;	Reference Example 1; 2,4-Dichloro-3-[2-(1 H-tetrazol-1-yl)ethoxy]benzoyl chloride (0.60 g) was dissolved in tetrahydrofuran (5 ml), this solution was added dropwise to a tetrahydrofuran (5 ml) solution of 1 ,3-dimethyl-5-hydroxypyrazole (0.22 g) and triethylamine (0.23 g) at 5C and the mixture was stirred at room temperature for 6 hours. After the reaction, the mixture was extracted with ethyl acetate (100 ml) and then washed with diluted hydrochloric acid and an aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off to obtain the desired 5-{2,4-dichloro-3-[2-(1 H-tetrazol-1-yl)ethyloxy]-benzoyloxy}-1 ,3-dimethylpyrazole (0.65 g). mp: 138-1400C.

Reference： [1]Patent: WO2008/43456,2008,A1 .Location in patent: Page/Page column 34

13
[ 1070761-75-9 ]
[ 5203-77-0 ]
C₁₅H₁₅F₃N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In dichloromethane; at 20℃; for 3h;	200 mg (0.71 mmol) of 2-methyl-3-methylsulfonyl-4-trifluoromethylbenzoic acid together with 87 mg (0.78 mmol) of 5-hydroxy-1,3-dimethylpyrazole and a catalytic amount of 4-N,N-dimethylaminopyridine were initially charged in 20 ml of dry CH2Cl2, and 163 mg (0.85 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added. The mixture was stirred at RT for 3 h, and 3 ml of 1 M HCl were then added. After phase separation, the aqueous phase was extracted with CH2Cl2. The organic phases were dried and concentrated. The residue was taken up in 20 ml of acetonitrile and 143 mg (1.42 mmol) of triethylamine, and eight drops of acetone cyanohydrine and a spatula tip of KCN were added. The mixture was stirred at RT for 16 h and concentrated. 15 ml of CH2Cl2 and then 2 ml of 1M HCl were added to the residue. After phase separation, the aqueous phase was extracted with CH2Cl2. The combined organic phases were dried and concentrated. The residue was purified chromatographically. What was isolated were 112.7 mg of pure product.

Reference： [1]Patent: US2009/69184,2009,A1 .Location in patent: Page/Page column 8

14
[ 1031359-55-3 ]
[ 5203-77-0 ]
C₁₇H₂₂N₂O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; for 5h;Reflux;	3-(2-Methoxyethoxy)-2-methyl-4-(methylsulfonyl)benzoic acid (1 g) was dissolved in chloroform (20 mL), and oxalyl chloride (500 mg) was added. A catalytic amount of dimethylformamide was added, followed by stirring at room temperature for 3 hours. Then, the solvent was distilled off under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (5 mL), and then a solution having 5-hydroxy-1 ,3-dimethylpyrazole (450 mg) dissolved in tetrahydrofuran (15 mL) was slowly added. Triethylamine (0.65 mL) was added, followed by heating and refluxing for 5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into water, then acidified with dilute hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was dissolved in acetonitrile (20 mL), and under cooling in an ice bath, triethylamine (0.65 mL) and acetone cyanohydrin (100 mg) were added, followed by stirring at room <n="26"/>temperature for 18 hours. The reaction solution was poured into water and washed with a small amount of ethyl acetate. Then, the aqueous layer was acidified with dilute hydrochloric acid. It was extracted with ethyl acetate, and then, the organic layer was washed with a saturated sodium chloride aqueous solution and then dried over magnesium sulfate. The solvent was distilled off 5 under reduced pressure. The obtained residue was purified by column chromatography (developing solvent: ethyl acetate) to obtain 5-hydroxy-1 ,3-dimethylpyrazol-4-yl 3-(2- methoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone (500 mg, the following Compound No. 5- 2) as slightly yellow solid.

Reference： [1]Patent: WO2009/142318,2009,A1 .Location in patent: Page/Page column 24-25

15
[ 1196958-20-9 ]
[ 5203-77-0 ]
[ 1196958-16-3 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 16h;	Step 6: Synthesis of 4-(4-chloro-3-ethylsulfinyl-2-methyl benzoyl)-5-hydroxy-1,3-dimethylpyrazole128 mg (1.14 mmol) of 5-hydroxy-1,3-dimethylpyrazole were added to 270 mg (purity 95% by weight; 1.04 mmol) of 4-chloro-3-ethylsulfinyl-2-methylbenzoic acid in 20 ml of dichloromethane (CH2Cl2). 239 mg (1.24 mmol) of 1-(3'-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added, and the mixture was stirred at RT for 16 h. For work-up, 3 ml of 1M HCl were added, and the organic phase was freed from the solvent. 210 mg (2.07 mmol) of triethylamine, 10 drops of acetone cyanohydrin and a spatula tip of potassium cyanide were added to the residue in 20 ml of acetonitrile. The reaction mixture was stirred at RT for 16 h and then freed from the solvent. The residue was stirred at RT with 25 ml of a mixture of aqueous saturated sodium bicarbonate solution and diethyl ether for 10 min. The phases were separated, and the aqueous phase was acidified with dilute HCl and then extracted with CH2Cl2. The organic phase was freed from the solvent and the residue was then purified chromatographically. This gave 100 mg of clean product.

Reference： [1]Patent: US2010/4129,2010,A1 .Location in patent: Page/Page column 8

16
C₁₁H₈ClF₅OS [ No CAS ]
[ 5203-77-0 ]
[ 1355157-60-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 16h;	Step 7: Synthesis of 1,3-dimethyl-5-(2-methyl-3-(methylthio)-4-(pentafluoroethyl)benzoyloxy)pyrazole360 mg (1.20 mmol) of 2-methyl-3-(methylthio)-4-(pentafluoroethyl)benzoic acid were introduced into 20 ml of dry dichloromethane and admixed in succession with 198 mg (1.56 mmol) of oxalyl dichloride and also with two drops of N,N-dimethyl-formamide. After the end of evolution of gas, the mixture was heated under reflux for 10 minutes. When a check on the reaction by thin-layer chromatography had indicated complete conversion, the contents were freed from the solvent, and the residue was then taken up in 20 ml of dry dichloromethane. The mixture was admixed with 161 mg (1.44 mmol) of 5-hydroxy-1,3-dimethylpyrazole, and then 243 mg (2.40 mmol) of triethylamine were added dropwise. The contents were stirred at RT for 16 hours. For working up, 3 ml of 1M hydrochloric acid were added, and, following phase separation, the organic phase was freed from the solvent. The residue, finally, was purified by chromatography, giving 410 mg of clean product.

Reference： [1]Patent: US2012/21903,2012,A1 .Location in patent: Page/Page column 10

17
[ 5203-77-0 ]
[ 552-89-6 ]
6-chloro-1,3-dimethyl-9-hydroxy-1H-pyrazolo[3,4-b]quinolin-4(9H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With hydrogenchloride; acetic acid; In water; for 24h;Reflux;	3.13 6-Chloro-1,3-dimethyl-9-hydroxy-1H-pyrazolo[3,4-b]quinolin-4(9H)-one (20) Nitrobenzaldehyde (27) (1.59 g, 10.5 mmol) was added to a stirred solution of 1-methyl-1H-pyrazol-5-ol (25a) (1.20 g, 10.5 mmol) in AcOH/HCl (concd) (1:1 v/v) and the mixture was heated at reflux for 24 h. After cooling, the precipitated solid was filtered, washed sequentially with H2O and MeOH and dried to give the title compound (1.54 g, 59%) as a yellow solid, mp 243-248 C (EtOH) (found: 264.0534. C12H11ClN3O2 [MH] requires 264.0533); FTIR (KBr)/cm-1 numax 2932, 2550, 1637, 1257, 1040, 881, 807; 1H NMR (400 MHz; CD3OD) delta 8.48 (1H, d, J 2, H-5), 7.35 (1H, d, J 9, H-8), 7.19 (1H, dd, J 9, 2, H-7), 3.45 (3H, s, NMe), 2.50 (3H, s, Me); 13C NMR (125 MHz; DMSO-d6) delta 162.6 (C), 155.6 (C), 144.3 (C), 132.9 (CH), 125.0 (C), 122.8 (CH), 115.9 (CH), 113.3 (C), 34.1 (Me), 13.8 (Me); LRMS (APcI) m/z (rel intensity) 264 (MH+, 100).

Reference： [1]Tetrahedron,2013,vol. 69,p. 8429 - 8438

18
[ 5203-77-0 ]
6-chloro-1,3-dimethyl-9-ethoxy-1H-pyrazolo[3,4-b]quinolin-4(9H)-one [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 8429 - 8438

19
[ 5203-77-0 ]
6-chloro-1,3-dimethyl-9-N-propoxy-1H-pyrazolo[3,4-b]quinolin-4(9H)-one [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 8429 - 8438

20
3-(3-bromophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(3-bromophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

21
3-(2-fluorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(2-fluorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

22
3-(2-methoxyphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
C₂₂H₂₀N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

23
3-(2-chloro-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(2-chloro-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

24
3-(4-methoxyphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(4-methoxyphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

25
3-(4-bromophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(4-bromophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

26
2-methyl-4-oxo-3-p-tolyl-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 2-methyl-4-oxo-3-p-tolyl-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

27
3-(4-fluorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(4-fluorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

28
3-(4-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(4-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

29
3-(2-fluoro-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(2-fluoro-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

30
3-(4-fluoro-2-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(4-fluoro-2-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

31
3-(4-chloro-2-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(4-chloro-2-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

32
3-(2-bromo-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(2-bromo-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

33
3-(2,4-dimethylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(2,4-dimethylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

34
3-(3-fluorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(3-fluorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

35
3-(3-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(3-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

36
3-(2-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 3-(2-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

37
2-methyl-4-oxo-3-o-tolyl-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 2-methyl-4-oxo-3-o-tolyl-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

38
2-methyl-4-oxo-3-m-tolyl-3,4-dihydroquinazoline-6-carboxylic acid [ No CAS ]
[ 5203-77-0 ]
1,3-dimethyl-1H-pyrazol-5-yl 2-methyl-4-oxo-3-m-tolyl-3,4-dihydroquinazoline-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%		Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then <strong>[5203-77-0]1,3-dimethyl-1H-pyrazol-5-ol</strong> (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5194 - 5211

39
3-(N-cyano-S-methylsulfonimidoyl)-2-methoxy-4-(trifluoromethyl)benzoic acid [ No CAS ]
[ 5203-77-0 ]
5-hydroxy-1,3-dimethyl-4-[3-(N-cyano-S-methylsulfonimidoyl)-2-methoxy-4-(trifluoromethyl)benzoyl]pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31.3 mg		165 mg (75% by weight; 0.384 mmol) of 3-(N-cyano-S-methylsulfonimidoyl)-2-methoxy-4-(trifluormethyl)benzoic acid and 68.9 mg (0.614 mmol) of 5-hydroxy-1,3-dimethylpyrazole were initially charged in 20 ml of dichlormethane, and 128 mg (0.666 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added. The mixture was stirred at RT for 16 h and, for work-up, washed with 1 M hydrochloric acid. After phase separation, the organic phase was dried, filtered and freed from the solvent on a rotary evaporator. The residue was purified chromatographically and the intermediate obtained was then dissolved in 15 ml of acetonitrile. 104 mg (1.02 mmol) of triethylamine, eight drops of trimethylcyanide and a spatula tip of potassium cyanide were then added. The mixture was stirred at RT for 16 h and, for work-up, freed from the solvent. The residue was taken up in dichloromethane and washed with 3 ml of 1M hydrochloric acid. After phase separation, the organic phase was freed from the solvent and the residue was purified chromatographically, which gave 31.3 mg of 5-hydroxy-1,3-dimethyl-4-[3-(N-cyano-S-methylsulfonimidoyl)-2-methoxy-4-(trifluoromethyl)benzoyl]pyrazole in a purity of 85% by weight.

Reference： [1]Patent: US2015/31536,2015,A1 .Location in patent: Paragraph 0080

40
[ 5203-77-0 ]
2-((5-(4-fluorophenoxy)-1,3-dimethyl-1H-pyrazol-4-yl)methylene)hydrazinecarboamide [ No CAS ]