Intermediate of preparing high-purity sulfonamide compound

Abstract

The present invention discloses a sulfonamide compound (III) which is intermediately produced in a process for preparing a high-purity sulfonamide compound (I). The preparation comprises the following steps: a, taking a crude product of a sulfonamide compound (I) as an initial raw material, and enabling the raw material to react with a compound of a formula (II) in presence of alkali and a catalyst so as to synthesize an intermediate of a formula (III); and b, enabling the compound represented by the formula (III) to react with alkali or acid, thereby obtaining the high-purity sulfonamide compound (I).

Claims

1. A sulfonamide compound (III), wherein the sulfonamide compound (III) is intermediately produced in a process for preparing a sulfonamide compound (I) having a purity of 99% or higher, wherein the process comprises: a. reacting with a compound (II), under the presence of a solvent, a base and a catalyst, a crude sulfonamide compound (I) as an initial raw material, so as to synthesize the sulfonamide compound (III); and b. reacting the sulfonamide compound (III) with a base or an acid in a solvent to obtain the sulfonamide compound (I) having a purity of 99% or higher; a reaction scheme is as follows: ##STR00007## wherein R is methyl, or aryl or heteroaryl selected from: ##STR00008## Ar is aryl or heteroaryl selected from: ##STR00009## X is halogen or tert-butoxy carbonyloxy; and Y is C.sub.1-C.sub.6 alkyl, C.sub.6-C.sub.12 aryl or tert-butoxy.

2. The sulfonamide compound (III) of claim 1, wherein Y is C.sub.1-C.sub.6 alkyl or tert-butoxy.

3. A sulfonamide compound of formula (III) ##STR00010## wherein R is methyl, or aryl or heteroaryl selected from: ##STR00011## Ar is aryl or heteroaryl selected from: ##STR00012## and Y is C.sub.1-C.sub.6 alkyl, C.sub.6-C.sub.12 aryl or tert-butoxy.

4. The sulfonamide compound of formula (III) of claim 3, wherein Y is C.sub.1-C.sub.6 alkyl or tert-butoxy.

5. The sulfonamide compound of formula (III) of claim 3, wherein R is ##STR00013## and Ar is selected from ##STR00014##

6. The sulfonamide of formula (III) of claim 5, wherein R is ##STR00015## and Ar is selected from ##STR00016##

7. The sulfonamide of formula (III) of claim 6, wherein R is ##STR00017## and Ar is ##STR00018##

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) To understand technical contents of the present invention more clearly, the present invention is further described with reference to the following embodiments, but the present invention is not limited by the following embodiments.

Embodiment 1 Preparation of N-acetyl-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(2) The preparation method comprises the following steps:

(3) sequentially adding a crude product of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (HPLC purity is 95.8%) (10.0 g, 1.0 eq), DMAP (0.01 g), acetonitrile (100 mL) and triethylamine (3.0 g, 1.2 eq) into a 250 mL reaction flask at room temperature, and dropwise adding acetyl chloride (2.1 g, 1.1 eq); continuously reacting for 3 h after finishing dropwise adding, stopping the reaction when the raw materials are completely reacted as determined by HPLC, distilling to remove the acetonitrile and adding water, extracting for three times with dichloromethane, merging organic phases, washing with brine and drying with anhydrous magnesium sulfate, washing the white solid obtained by filtering and concentrating with ethanol, and drying to obtain 10.3 g of the white solid, the HPLC purity is 99.1%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.72 (m, 2H), 7.62 (m, 1H), 7.50 (s, 1H), 4.73 (m, 2H), 2.12 (s, 3H), 1.48 (m, 3H).

Embodiment 2 Preparation of N-(2-bromoacetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(4) The preparation method comprises the following steps:

(5) sequentially adding a crude product of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (HPLC purity of 95.8%) (10.0 g, 1.0 eq), DMAP (0.01 g), THF (100 mL) and triethylamine (3.0 g, 1.2 eq) into a 250 mL reaction flask at room temperature, and dropwise adding bromoacetyl bromide (5.5 g, 1.1 eq); continuously reacting for 2 h after finishing dropwise adding, stopping the reaction when the raw materials are completely reacted as determined by HPLC, distilling to remove the THF and adding water, extracting for three times with dichloromethane, merging organic phases, washing with brine and then drying with anhydrous magnesium sulfate, washing the white solid obtained by filtering and concentrating with ethanol, and drying to obtain 12.3 g of the white solid, wherein the HPLC purity is 99.5%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.76 (m, 2H), 7.68 (m, 1H), 7.57 (s, 1H), 4.87 (s, 2H), 4.76 (m, 2H), 1.50 (m, 3H).

Embodiment 3 Preparation of N-(2-chloracetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(6) The preparation method comprises the following steps:

(7) sequentially adding a crude product of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (HPLC purity of 95.8%) (10.0 g, 1.0 eq), DMAP (0.01 g), THF (100 mL) and triethylamine (3.0 g, 1.2 eq) into a 250 mL reaction flask at room temperature, and dropwise adding chloroacetyl chloride (3.1 g, 1.1 eq); continuously reacting for 2 h after finishing dropwise adding, stopping the reaction when the raw materials are completely reacted as determined by HPLC, distilling to remove the THF and adding water, extracting for three times with dichloromethane, merging organic phases, washing with brine and then drying with anhydrous magnesium sulfate, washing the white solid obtained by filtering and concentrating with ethanol, and drying to obtain 11.4 g white solid, wherein the HPLC purity is 99.3%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.72 (m, 2H), 7.62 (m, 1H), 7.50 (s, 1H), 4.97 (s, 2H), 4.73 (m, 2H), 1.48 (m, 3H).

Embodiment 4 Preparation of N-(2,2-dichloroacetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(8) The preparation method comprises the following steps:

(9) sequentially adding a crude product of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (HPLC purity is 95.8%) (10.0 g, 1.0 eq), DMAP (0.01 g), THF (100 mL) and triethylamine (3.0 g, 1.2 eq) into a 250 mL reaction flask at room temperature, and dropwise adding dichloroacetyl chloride (4.0 g, 1.1 eq); continuously reacting for 1 h after finishing dropwise adding, stopping the reaction when the raw materials are completely reacted as determined by HPLC, distilling to remove the THF and adding water, extracting for three times with dichloromethane, merging organic phases, washing with brine and then drying with anhydrous magnesium sulfate, washing the white solid obtained by filtering and concentrating with ethanol, and drying to obtain 11.6 g white solid, and the HPLC purity is 99.0%. .sup.1H NMR (400 MHz, D6-DMSO) :7.75 (m, 2H), 7.63 (m, 1H), 7.54 (s, 1H), 6.80 (s, 1H), 4.78 (m, 2H), 1.46 (m, 3H).

Embodiment 5 Preparation of N-benzoyl-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(10) N-benzoyl-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, it is a white solid and the HPLC purity is 98.7%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.95-6.86 (m, 9H), 3.98 (m, 2H), 1.33 (m, 3H).

Embodiment 6 Preparation of N-(2-methoxyacetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(11) N-(2-methoxyacetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, it is a white solid and the HPLC purity is 98.8%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.70-7.71 (m, 2H), 7.60-7.61 (m, H), 7.49 (s, H), 4.74 (q, 2H), 4.57 (s, 3H), 1.47 (t, 3H).

Embodiment 7 Preparation of 2-(2,2-difluoroethoxyl)-N-(2-chloracetyl)-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl benzenesulfonamide

(12) 2-(2,2-difluoroethoxyl)-N-(2-chloracetyl)-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl benzenesulfonamide is prepared by a method similar to that in embodiment 1, it is a white solid and the HPLC purity is 98.9%. NMR (400 MHz, D6-DMSO) : 7.72-7.96 (m, 4H), 6.75 (t, 1H), 4.77 (m, 2H), 4.35 (s, 2H), 4.20 (s, 3H), 4.04 (s, 3H).

Embodiment 8 Preparation of 2-(2,2-difluoroethoxyl)-N-acetyl-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl Benzenesulfonamide

(13) 2-(2,2-difluoroethoxyl)-N-acetyl-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl benzenesulfonamide is prepared by a method similar to that in embodiment 1, it is a white solid, and the HPLC purity is 98.7%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.70-7.92 (m, 4H), 6.76 (t, 1H), 4.78 (m, 2H), 4.20 (s, 3H), 4.02 (s, 3H), 1.95 (s, 3H).

Embodiment 9 Preparation of 2-(2,2-difluoroethoxyl)-N-benzoyl-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl Benzenesulfonamide

(14) 2-(2,2-difluoroethoxyl)-N-benzoyl-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl benzenesulfonamide is prepared by a method similar to that in embodiment 1, it is a white solid, and the HPLC purity is 99.0%. NMR (400 MHz, D6-DMSO) : 7.31-7.96 (m, 9H), 6.35 (t, 1H), 4.64 (m, 2H), 4.13 (s, 3H), 3.94 (s, 3H).

Embodiment 10 Preparation of 2-(2,2-difluoroethoxyl)-N-(2-methoxyacetyl)-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl Benzenesulfonamide

(15) 2-(2,2-difluoroethoxyl)-N-(2-methoxyacetyl)-N-(5,8-dimethoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)-6-trifluoromethyl benzenesulfonamide is prepared by a method similar to that in embodiment 1, it is a white solid, and the HPLC purity is 98.8%. NMR (400 MHz, D6-DMSO) : 7.70-7.92 (m, 4H), 6.70 (t, 1H), 4.74 (m, 2H), 4.17 (s, 3H), 3.99 (s, 3H), 3.82 (s, 2H), 3.13 (s, 3H).

Embodiment 11 Preparation of N-(2-methoxyacetyl)-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl benzoate

(16) N-(2-methoxyacetyl)-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl benzoate is prepared by a method similar to that in embodiment 1, and the HPLC purity is 95.9%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.99 (t, 2H), 7.73 (t, 1H), 7.46 (s, 1H), 4.74 (q, 2H), 3.69 (s, 1H), 3.67 (s, 3H), 3.28 (s, 3H), 1.98 (s, 1H), 1.50 (t, 3H).

Embodiment 12 Preparation of N-benzoyl-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl Benzoate

(17) N-benzoyl-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl benzoate is prepared by a method similar to that in embodiment 1, and the HPLC purity is 99.1%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.87-7.89 (m, 2H), 7.60-7.62 (m, 1H), 7.52-7.53 (m, 2H), 7.40-7.43 (m, 2H), 7.28-7.31 (m, 2H), 4.74 (q, 2H), 3.78 (s, 3H), 1.51 (t, 3H).

Embodiment 13 Preparation of N-acetyl-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl Benzoate

(18) N-acetyl-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl benzoate is prepared by a method similar to that in embodiment 1, and the HPLC purity is 99.2%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.94-7.98 (m, 2H), 7.71 (t, 1H), 7.45 (s, 1H), 4.73 (t, 2H), 3.66 (s, 3H), 1.49 (t, 3H).

Embodiment 14 Preparation of N-(2-chloracetyl)-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl Benzoate

(19) N-(2-chloracetyl)-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl benzoate is prepared by a method similar to that in embodiment 1, and the HPLC purity is 98.2%. .sup.1H NMR (400 MHz, D6-DMSO) : 7.97-8.02 (m, 2H), 7.76 (t, 1H), 7.46 (s, 1H), 4.73 (q, 2H), 3.66 (s, 3H), 1.50 (t, 3H).

Embodiment 15 Preparation of N-(2,2-dichloroacetyl)-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl Benzoate

(20) N-(2,2-dichloroacetyl)-3-chloro-2-[(5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-yl)sulfonamide]methyl benzoate is prepared by a method similar to that in embodiment 1, and the HPLC purity is 97.1%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.00-8.05 (m, 2H), 7.78 (t, 1H), 7.41 (s, 1H), 4.73 (q, 2H), 3.67 (s, 3H), 1.51 (t, 3H).

Embodiment 16 Preparation of N-(2-methoxyacetyl)-N-[2,4-dichloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane Sulfonamide

(21) N-(2-methoxyacetyl)-N-[2,4-dichloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane sulfonamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 95.9%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.19 (s, 1H), 8.10 (s, 1H), 7.46-7.65 (m, 1H), 3.96-3.98 (m, 1H), 3.80-3.83 (m, 1H), 3.62 (s, 3H), 3.26 (s, 3H), 2.42 (s, 3H).

Embodiment 17 Preparation of N-benzoyl-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane Sulfonamide

(22) N-benzoyl-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane sulfonamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 99.8%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.22 (s, 1H), 7.97 (s, 1H), 7.54 (s, 2H), 7.48 (t, 2H), 7.34 (t, 2H), 7.31 (t, 2H), 3.70 (s, 3H), 2.40 (s, 3H).

Embodiment 18 Preparation of N-acetyl-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane Sulfonamide

(23) N-acetyl-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane sulfonamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 99.8%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.20 (s, 1H), 8.08 (s, 1H), 7.46-7.64 (m, 1H), 3.60 (s, 3H), 2.42 (s, 3H), 2.00 (s, 3H).

Embodiment 19 Preparation of N-(2-chloracetyl)-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane Sulfonamide

(24) N-(2-chloracetyl)-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane sulfonamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 95.8%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.19 (s, 1H), 8.10 (s, 1H), 7.48-7.65 (m, 1H), 4.27 (s, 2H), 3.64 (s, 3H), 2.42 (s, 3H).

Embodiment 20 Preparation of N-(2,2-dichloroacetyl)-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane Sulfonamide

(25) N-(2,2-dichloroacetyl)-N-[2,4-dichloro-5-(4-difluromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl]methane sulfonamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 95.8%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.19 (s, 1H), 8.17 (s, 1H), 7.65 (s, 1H), 7.46-7.66 (m, 1H), 6.65 (s, 1H), 3.70 (s, 3H), 2.42 (s, 3H).

Embodiment 21 Preparation of N-(2-methoxy acetyl)-N-(2,6-difluorophenyl)-5-ethoxy-8-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(26) N-(2-methoxyacetyl)-N-(2,6-difluorophenyl)-5-ethoxy-8-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 98.6%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.41 (d, 1H), 7.71-7.74 (m, 1H), 7.41 (t, 2H), 4.35 (s, 2H), 4.26 (s, 3H), 3.25 (s, 3H).

Embodiment 22 Preparation of N-benzoyl-N-(2,6-difluorophenyl)-5-ethoxy-8-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(27) N-benzoyl-N-(2,6-difluorophenyl)-5-ethoxy-8-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 98.5%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.40 (d, 1H), 7.56-7.59 (m, 1H), 7.51 (t, 2H), 7.42 (d, 1H), 7.37 (t, 2H), 7.28 (t, 2H), 4.27 (s, 3H).

Embodiment 23 Preparation of N-acetyl-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide

(28) The N-acetyl-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 97.9%. .sup.1H NMR (400 MHz, D6-DMSO) : 9.45 (d, 1H), 7.66 (d, 1H), 7.55 (d, 1H), 7.36 (t, 2H), 7.36 (t, 2H), 2.71 (s, 3H), 2.38 (s, 3H).

Embodiment 24 Preparation of N-(2-chloracetyl)-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide

(29) N-(2-chloracetyl)-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 99.2%. .sup.1H NMR (400 MHz, D6-DMSO) : 9.46 (d, 1H), 7.70-7.73 (m, 1H), 7.57 (d, 1H), 7.38 (t, 2H), 4.27 (s, 2H), 2.69 (s, 3H).

Embodiment 25 Preparation of N-(2,2-dichloroacetyl)-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide

(30) N-(2,2-dichloroacetyl)-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 97.2%. .sup.1H NMR (400 MHz, D6-DMSO) : 9.45 (d, 1H), 7.71 (d, 1H), 7.55 (d, 1H), 7.36 (t, 2H), 7.17 (s, 1H), 2.69 (s, 3H).

Embodiment 26 Preparation of N-(2-methoxy acetyl)-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide

(31) N-(2-methoxyacetyl)-N-(2,6-difluorophenyl)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 98.8%. .sup.1H NMR (400 MHz, D6-DMSO) : 9.45 (d, 1H), 7.68-7.70 (m, 1H), 7.55 (d, 1H), 7.36 (t, 2H), 4.50 (s, 2H), 3.28 (s, 3H), 2.71 (s, 3H).

Embodiment 27 Preparation of N-acetyl-N-(2,6-difluorophenyl)-5-ethoxy-8-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(32) N-acetyl-N-(2,6-difluorophenyl)-5-ethoxy-8-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 99.3%. .sup.1H NMR (400 MHz, D6-DMSO) : 8.41 (d, 1H), 7.69-7.72 (m, 1H), 7.41 (t, 2H), 4.25 (s, 3H), 2.33 (s, 3H).

Embodiment 28 Preparation of N-t-butyloxycarbory 1-N-(2,6-difluorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(33) N-t-butyloxycarboryl-N-(2,6-difluorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide is prepared by a method similar to that in embodiment 1, and the HPLC purity is 96.8%. .sup.1H NMR (400 MHz, D6-DMSO) : 1.43 (t, 3H), 1.67 (s, 9H), 4.78 (q, 2H), 6.82 (s, 1H), 7.22 (t, 1H), 7.35 (d, 2H).

Embodiment 29 Preparation of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(34) The preparation method comprises the following steps:

(35) adding the N-t-butyloxycarboryl-N-(2,6-difluorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (5.06 g, 1.0 eq) prepared in embodiment 28, 1 mL of concentrated hydrochloric acid and ethanol (50 mL) into a 250 mL reaction flask equipped with a mechanical stirrer, raising the temperature to 60 C. and continuously stirring and reacting for about 2 h, cooling the reaction solution to room temperature when the raw materials are completely reacted as determined by HPLC, filtering, washing a filter cake with little ethanol, and drying to a constant weight to obtain 3.97 g white solid with HPLC purity of 99.9%. .sup.1H NMR (400 MHz, D6-DMSO) : 11.05 (s, 1H), 7.51 (m, 2H), 7.37 (m, 2H), 4.65 (m, 2H), 1.47 (m, 3H).

Embodiment 30 Preparation of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(36) The preparation method comprises the following steps:

(37) adding the N-acetyl-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (10.3 g, 1.0 eq) prepared in embodiment 1, anhydrous sodium carbonate (2.4 g, 1.0 eq) and absolute methanol (100 mL) into a 250 mL reaction flask equipped with a mechanical stirrer, raising the temperature to 55 C. and continuously stirring and reacting for about 5 h, cooling a reaction solution to room temperature when the raw materials are completely reacted as determined by HPLC, filtering, washing a filter cake with cold water, and drying to a constant weight to obtain 8.3 g white solid with HPLC purity of 99.9%. .sup.1H NMR (400 MHz, D6-DMSO) : 11.05 (s, 1H), 7.51 (m, 2H), 7.37 (m, 2H), 4.65 (m, 2H), 1.47 (m, 3H).

Embodiment 31 Preparation of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(38) The preparation method comprises the following steps:

(39) adding the N-(2-bromoacetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (12.3 g, 1.0 eq) prepared in embodiment 2, sodium bicarbonate (2.0 g, 1.0 eq) and absolute isopropanol (100 mL) into a 250 mL reaction flask equipped with a mechanical stirrer, raising the temperature to 60 C. and continuously stirring and reacting for about 6 h, cooling a reaction solution to room temperature when the raw materials are completely reacted as determined by HPLC, filtering, washing the filter cake with cold water, filtering, and drying to a constant weight to obtain 8.0 g white solid with HPLC purity of 99.9%. .sup.1H NMR (400 MHz, D6-DMSO) : 11.05 (s, 1H), 7.51 (m, 2H), 7.37 (m, 2H), 4.65 (m, 2H), 1.47 (m, 3H).

Embodiment 32 Preparation of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(40) The preparation method comprises the following steps:

(41) adding the N-(2-chloracetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (11.4 g, 1.0 eq) prepared in embodiment 3, potassium carbonate (3.2 g, 1.0 eq) and absolute ethyl alcohol (100 mL) into a 250 mL reaction flask equipped with a mechanical stirrer, raising the temperature to 60 C. and continuously stirring and reacting for about 6 h, cooling a reaction solution to room temperature when the raw materials are completely reacted as determined by HPLC, filtering, washing the filter cake with cold water, filtering, and drying to a constant weight to obtain 8.4 g white solid with HPLC purity of 99.9%. .sup.1H NMR (400 MHz, D6-DMSO) : 11.05 (s, 1H), 7.51 (m, 2H), 7.37 (m, 2H), 4.65 (m, 2H), 1.47 (m, 3H).

Embodiment 33 Preparation of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide

(42) The preparation method comprises the following steps:

(43) adding the N-(2,2-dichloroacetyl)-N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfamide (11.6 g, 1.0 eq) prepared in embodiment 4, potassium carbonate (2.0 g, 1.0 eq) and absolute ethyl alcohol (100 mL) into a 250 mL reaction flask equipped with a mechanical stirrer, raising the temperature to 60 C. and continuously stirring and reacting for about 6 h, cooling a reaction solution to room temperature when the raw materials are completely reacted as determined by HPLC, filtering, washing the filter cake with cold water, filtering, and drying to a constant weight to obtain 7.9 g white solid with HPLC purity of 99.9%. NMR (400 MHz, D6-DMSO) : 11.05 (s, 1H), 7.51 (m, 2H), 7.37 (m, 2H), 4.65 (m, 2H), 1.47 (m, 3H).