Diisopropylethylamine → N-(4-Chloro-3-(5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl)benzyl)isoxazole-5-carboxamide

HRID 59512

Reaction equation

HRID 59512 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([Cl:25])=[C:7]([C:9]2[NH:13][C:12](=[O:14])[N:11]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[N:10]=2)[CH:8]=1.CCN(C(C)C)C(C)C.[O:35]1[C:39]([C:40](Cl)=[O:41])=[CH:38][CH:37]=[N:36]1>C1COCC1>[Cl:25][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:40]([C:39]2[O:35][N:36]=[CH:37][CH:38]=2)=[O:41])=[CH:8][C:7]=1[C:9]1[NH:13][C:12](=[O:14])[N:11]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:20]=2)[N:10]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2736707Isoxazole-5-carbonyl chlorideHCID 1364923713-(5-(aminomethyl)-2-chlorophenyl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one

Product 1

HCID 136246114N-(4-Chloro-3-(5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl)benzyl)isoxazole-5-carboxamideYield 39.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(5-(aminomethyl)-2-chlorophenyl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one (Intermediate-63, 0.060 g, 0.162 mmol) in dry THF (5 mL) was added DIPEA (3 mL) and stirred for 20 minutes. The reaction mixture was cooled to 0° C. and isoxazole-5-carbonyl chloride (0.032 g, 0.243 mmol) was added and stirred for 3 h at room temperature. The reaction mass was quenched in water, extracted with DCM:MeOH and concentrated to afford crude product which was purified by column chromatography eluting with MeOH:DCM to afford 0.030 g of pure product. 1H NMR (400 MHz, DMSO d6): δ 4.50-4.52 (d, J=8 Hz, 2H), 7.09-7.10 (d, J=2 Hz, 1H), 7.43-7.45 (d, J=8.4 Hz, 1H), 7.50-7.53 (d, J=10.4 Hz, 1H), 7.59-7.64 (d, J=18 Hz, 1H), 7.82-7.85 (d, J=8.8 Hz, 2H), 8.17-8.19 (d, J=8.4 Hz, 2H), 8.74-8.75 (d, J=2 Hz, 1H), 9.58-9.61 (t, 1H), 12.61-12.74 (br s, 1H); MS (m/z): 464.11 (M+H+).

Workup

  1. stirringstirred for 3 h at room temperature
  2. customThe reaction mass was quenched in water
  3. extractionextracted with DCM
  4. concentrationMeOH and concentrated
  5. customto afford crude product which
  6. customwas purified by column chromatography
  7. washeluting with MeOH

Sources & evidence

ORD record
ord-e19bdcbc4255402fb94dbc43971d2d45
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Linked notes

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