Method for preparing 2-chloro-n-(1-cyanocyclopropyl)-5-[2′-methyl-5′-(pentafluoroethyl)-4′-(trifluoromethyl)-2′h-1,3′-bipyrazol-4-yl]benzamide

Abstract

The present invention relates to a method for preparing 2-chloro-N-(1-cyanocyclopropyl)-5-[2-methyl-5-(pentafluoroethyl)-4-(trifluoromethyl)-2H-1,3-bipyrazol-4-yl]benzamide, i.e. the compound of the formula (I) and to a method for purifying the compound of the formula I. The present invention additionally relates to new crystal forms of the compound of the formula I. ##STR00001##

Claims

1. A method for preparing a compound of formula (I) ##STR00018## by reacting a compound of formula (VI) ##STR00019## where A is a boron-containing substituent selected from the group consisting of: a boronic acid radical of the formula ##STR00020## a trifluoroborate of the formula
-BF.sub.3M, where M is an alkali metal salt, and a boronic ester of the formula ##STR00021## where R.sup.1 and R.sup.2 are independently C.sub.1-C.sub.6 alkyl or C.sub.3-C.sub.6 cycloalkyl, or R.sup.1 and R.sup.2 together form a C.sub.1-C.sub.6 alkylene group optionally substituted by one or more C.sub.1-C.sub.4 alkyl groups, with a compound of formula (VII) ##STR00022## where X is a reactive group selected from: bromine, iodine and a radical OSO.sub.2Y, where Y is C.sub.1-C.sub.8 perfluoroalkyl, in the presence of a base and a catalyst, wherein compound VI is used in amounts of 0.7 to 1.3 equivalents based on the structural unit of the formula VII; wherein the base[s] used are alkali metal carbonates, alkaline earth metal carbonates, alkali metal hydrogen carbonates, alkaline earth metal hydrogen carbonates, alkali metal phosphates, alkaline earth metal phosphates, alkali metal fluorides, or mixtures thereof and is used in an amount of 1 to 10 equivalents based on the starting material of the formula VI.

2. The method according to claim 1, wherein R.sup.1 and R.sup.2 together form a C.sub.1-C.sub.6 alkylene group substituted by one or more C.sub.1-C.sub.2 alkyl groups.

3. The method according to claim 1, wherein X is bromine or iodine.

4. The method according to claim 1, wherein the reacting further occurs in the presence of a solvent, wherein the solvent used is dimethylformamide, dimethylacetamide, N-methylpyrrolidone, open-chain or cyclic ethers, or a C.sub.1-C.sub.6 alkyl-derived alcohol.

5. The method according to claim 1, wherein the catalyst comprises a palladium-containing component.

6. The method according to claim 5, wherein the catalyst additionally comprises a phosphorus-containing component.

7. The method according to claim 1, wherein the base is used in an amount of 2 to 5 equivalents based on the starting material of formula VI.

8. A method for purifying the compound of formula I, wherein the compound is the crystallized form of a compound of formula (I) modification I, the method comprising: crystallizing the compound from an aromatic hydrocarbon, wherein the aromatic hydrocarbon is selected from the group consisting of toluene, ethylbenzene, ortho-xylene, meta-xylene, and para-xylene.

9. The method according to claim 1, wherein a method of purification is executed subsequently to the reaction.

10. A crystalline form of a compound of formula (I) modification I.

11. The method according to claim 1, where M is sodium or potassium.

12. The method according to claim 1, wherein the base is used in an amount of 2.5 to 3.5 equivalents.

13. The method according to claim 4, wherein the solvent is a C.sub.1-C.sub.4 alkyl-derived alcohol.

Description

MEASUREMENT CONDITIONS

(1) TABLE-US-00002 Anode material Cu K-Alpha1 [] 1.54060 Generator 40 mA, 40 kV Sample rotation Yes Scan-axis Gonio Start position [2theta] 2.0066 End position [2theta] 37.9906

(2) FIG. 1: X-ray powder diffractogram of modification I

(3) FIG. 2: X-ray powder diffractogram of modification II

(4) FIG. 3: X-ray powder diffractogram of the ethanol-water inclusion complex

(5) FIG. 4: X-ray powder diffractogram of the amorphous form

(6) TABLE-US-00003 TABLE 2 IR spectroscopic data of the crystal forms of the compound of the formula (I) Bands [signal maxima in cm.sup.1] Ethanol-water Mod. I Mod. II inclusion complex Amorphous form 3249 3274 3252 3420 3120 3123 3119 3278 3019 3019 3097 3211 1660 1662 1730 3186 1599 1593 1661 2995 1562 1559 1600 2948 1509 1540 1585 2915 1474 1506 1561 1617 1430 1472 1509 1604 1399 1429 1473 1576 1375 1395 1429 1545 1341 1374 1394 1519 1308 1339 1374 1501 1276 1303 1343 1463 1255 1251 1307 1445 1218 1217 1275 1419 1180 1178 1255 1382 1145 1142 1218 1347 1099 1097 1205 1304 1060 1059 1187 1284 1053 1025 1137 1240 1027 991 1099 1226 993 966 1080 1200 968 941 1060 1180 943 897 1052 1169 899 866 1027 1143 864 837 992 1128 839 819 968 1089 821 802 943 1069 804 782 899 1047 184 769 865 1036 772 745 839 997 760 731 821 940 745 719 803 923 731 695 784 874 698 667 771 854 667 660 745 808 660 635 731 788 636 626 720 753 626 591 697 744 592 570 681 726 572 564 667 721 564 557 659 685 557 636 659 626 609 604 580 592 563 573 564 557

(7) Measurement conditions:

(8) ATR IR spectra were recorded at room temperature in a Tensor 37 FT-IR spectrophotometer from Bruker using an ATR unit and without further sample preparation. The resolution was 4 cm.sup.1.

(9) The spectra are shown in the figures:

(10) FIG. 5: IR spectrum of modification I

(11) FIG. 6: IR spectrum of modification II

(12) FIG. 7: IR spectrum of the ethanol-water inclusion complex

(13) FIG. 8: IR spectrum of the amorphous phase