JP2002234843A5 - - Google Patents

Description

Example 15
4- [2- [4- (Trifluoromethyl) pyridin-3-yl] -1,3-thiazol-4-yl] aniline (156)
Compound (59) (0.61 g, 1.72 mmol) was dissolved in formic acid (10 ml), Pd-C (0.06 g, 10 wt.%) Was added, and the mixture was stirred under hydrogen atmosphere at normal temperature and pressure for 2 hours. After removing the catalyst and the like by filtration, formic acid was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried (MgSO ₄ ) and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain white crystals (0.23 g, 42%).
Melting point 71-72 ° C
Elemental analysis value C ₁₅ H ₁₀ N ₃ S F ₃
C (%) H (%) N (%)
Calculated value: 56.07; 3.14; 13.08
Found: 56.08; 3.09; 13.12
¹ H-NMR (200 Hz, CDCl ₃ ) δ: 3.80 (2 H, s), 6. 76 (2 H, d, J = 8.8 Hz), 7. 48 (1 H, s), 7. 70 (1 H, d, J = 5.2 Hz), 7.77 (2H, d, J = 8.8 Hz), 8.87 (1 H, d, J = 5.2 Hz), 9.05 (1 H, s)

Example 16
3- [2- [4- (Trifluoromethyl) pyridin-3-yl] -1,3-thiazol-4-yl] aniline (157)
A colorless amorphous (0.94 g, quant.) Was obtained from compound (60) (1.00 g, 2.85 mmol) in the same manner as the method described in Example 15.
Elemental analysis value C ₁₅ H ₁₀ N ₃ S F ₃
C (%) H (%) N (%)
Calculated value: 56.07; 3.14; 13.08
Found: 56.00; 3.23; 13.02
¹ H-NMR (200 Hz, CDCl ₃ ) δ: 3.64 (2 H, s), 6.71 (1 H, d, J = 7.6 Hz), 7.19-7.35 (3 H, m), 7.65 (1 H, s), 7.70 (1 H , d, J = 5.2 Hz), 8. 88 (1 H, d, J = 5.2 Hz), 9.04 (1 H, s)

Example 18
N- (3- [2- [4- (Trifluoromethyl) pyridin-3-yl] -1,3-thiazol-4-yl] phenyl) acetamide hydrochloride (159)
A colorless amorphous (0.30 g, 70%) was obtained from compound (157) (0.38 g, 1.18 mmol) in the same manner as the method described in Example 17. Under ice-cooling, 4N ethyl acetate hydrochloric acid (0.22 ml) was added to a solution of this amorphous methanol (3 ml) and stirred at the same temperature for 10 minutes. The reaction mixture was concentrated under reduced pressure, and the obtained residue was crystallized from ethyl acetate-methanol to give hydrochloride as yellow needles.
Melting point 154-155 ° C
Elemental analysis value C ₁₇ H ₁₂ N ₃ OSF ₃ · HCl · 0.1 H ₂ O
C (%) H (%) N (%)
Calculated value: 50.84; 3.31; 10.45
Found: 50.76; 3.54; 10.36
¹ H-NMR (200 Hz, CDCl ₃ ) δ: 2.21 (3 H, s), 7.38-7.46 (2 H, m), 7.62-7.64 (4 H, m), 8.06 (1 H, s), 8. 90 (1 H, d, J = 4.8 Hz), 9.05 (1 H, s)

Example 19
N- (4- [2- [4- (Trifluoromethyl) pyridin-3-yl] -1,3-thiazol-4-yl] phenyl) methanesulfonamide hydrochloride (160)
A colorless amorphous (0.25 g, 72%) was obtained from compound (156) (0.28 g, 0.87 mmol) using methanesulfonyl chloride instead of acetyl chloride in the same manner as described in Example 17. Under ice-cooling, 4N ethyl acetate hydrochloric acid (0.16 ml) was added to a solution of this amorphous methanol (3 ml) and stirred at the same temperature for 10 minutes. The reaction mixture was concentrated under reduced pressure, and the obtained residue was crystallized from ethyl acetate-methanol to give hydrochloride as yellow crystals.
Melting point 205-207 ° C
Elemental analysis value C ₁₆ H ₁₂ N ₃ O ₂ S ₂ F ₃ · HCl
C (%) H (%) N (%)
Calculated value: 44.09; 3.01; 9.64
Found: 44.07; 2.97; 9.69
¹ H-NMR (200 Hz, CDCl ₃ ) δ: 3.06 (3 H, s), 6.45 (1 H, s), 7.31 (2 H, d, J = 8.8 Hz), 7.67 (1 H, s), 7.73 (1 H, d , J = 4.8 Hz), 7.98 (2 H, d, J = 8.8 Hz), 8. 91 (1 H, d, J = 4.8 Hz), 9.06 (1 H, s)

Example 20
N- (3- [2- [4- (trifluoromethyl) pyridin-3-yl] -1,3-thiazol-4-yl] phenyl) methanesulfonamide hydrochloride (161)
A colorless amorphous (0.28 g, 70%) was obtained from compound (157) (0.31 g, 0.96 mmol) using methanesulfonyl chloride instead of acetyl chloride in the same manner as described in Example 17. To this amorphous ethyl acetate (2 ml) solution was added 4N ethyl acetate hydrochloric acid (0.18 ml) under ice cooling, and the mixture was stirred at the same temperature for 10 minutes. The reaction solution was concentrated under reduced pressure, and the obtained residue was crystallized from ethyl acetate to give hydrochloride as yellow crystals.
Melting point 162-165 ° C
Elemental analysis value C ₁₆ H ₁₂ N ₃ O ₂ S ₂ F ₃ · HCl
C (%) H (%) N (%)
Calculated value: 44.09; 3.01; 9.64
Found: 44.02; 2.28; 9.63
¹ H-NMR (200 Hz, CDCl ₃ ) δ: 3.06 (3H, s), 6.66 (1H, s), 7.27-7.42 (1H, m), 7.46 (1H, t, J = 7.9 Hz), 7.72-7.84 (4H, m), 8. 91 (1 H, d, J = 5.6 Hz), 9.05 (1 H, s)

Claims (1)

R ^1c is 1) a carbamoyl group optionally having C _1-4 alkyl or C _7-9 aralkyl as a substituent, or 2) a C _1-4 alkylsulfonyl group, or substitution at a carbon atom adjacent to each other And two R ^{1b 's} are bonded to each other to represent a C _1-2 alkylenedioxy group, and R ^2a and R ^2b are the same or different and each has 1) a hydrogen atom and 2) halogen or hydroxy as a substituent C _1-4 alkyl, 3) carboxyl group or C _1-4 alkoxycarbonyl group, 4) carbamoyl group optionally having C _1-4 alkyl or C _7-9 aralkyl as a substituent, 5) substitution Amino group which may have C _1-4 alkyl, carbamoyl-C _1-4 alkyl or C _7-10 aralkyl as a group, 6) piperidino group or morpholino group, 7) C _1-4 alkylthio group or 8) Or a C _1-4 alkoxy group, or R ^2a and R ^{2 b} combine to form a butadienylene group, R ³ is 1) a hydrogen atom, 2) a halogen atom, 3) a C _1-4 alkyl group Or 4) a carboxyl group or 5) a C _1-4 alkoxycarbonyl group.