Hydrochloric Acid → 2-methyl-N-(thietan-3-yl)-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzamide

HRID 1770643노트

반응식

HRID 1770643 반응식
[CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C@:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C)C=O.C(Cl)(=O)C(Cl)=O.Cl.[OH-].[Na+].C(N(CC)CC)C.[S:50]1[CH2:53][CH:52]([NH2:54])[CH2:51]1>ClCCl>[CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C@:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:18])([F:19])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH:54][CH:52]1[CH2:53][S:50][CH2:51]1)=[O:6]

참가 물질

9

반응물 7

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 14594132Thietan-3-amineHCID 867270182-methyl-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzoic acid

생성물 1

HCID 867270192-methyl-N-(thietan-3-yl)-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
30 °C

실험 절차

To a solution of 2-methyl-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzoic acid (28.72 mmol, 13 g) in dichloromethane (100 mL) and N,N-dimethylformamide (0.2867 mmol, 0.0210 g) was added oxalyl chloride (4.836 g) dropwise at room temperature and under argon (the liberated hydrochloric acid gas was scrubbed with a sodium hydroxide 0.5N solution). The mixture was stirred at room temperature for 1 h and at 30° C. for 20 min until the gas evolution ceased. The reaction mixture was concentrated to dryness and redissolved in dichloromethane (100 mL), triethylamine (71.81 mmol, 7.340 g) was added at 0-5° C. under argon followed by dropwise addition of thietan-3-amine (28.72 mmol, 2.561 g). The mixture was allowed to warm to room temperature and stirred for 16 h. The mixture was extracted with aqueous hydrochloric acid (0.5N), water, brine, dried over MgSO4, filtered and evaporated affording the crude product. Purification over silica gel (eluent: CH2Cl2/EtOAc) yielded the title compound. LCMS (Method GR) RT 1.25 min, [M+H]+ 523/525; 1H-NMR (CDCl3, 400 MHz): 2.45 (s, 3H), 3.35 (m, 2H), 3.50 (m, 2H), 3.60 (d, 1H), 74.10 (d, 1H), 5.40 (q, 1H), 6.20 (d, NH), 7.40 (s, 1H), 7.51 (d, 1H), 7.40 (s, 1H), 7.50 (s, 2H), 7.65 (s, 2H). 19F-NMR (CDCl3, 376 MHz): −79.43.

후처리

  1. concentrationThe reaction mixture was concentrated to dryness
  2. dissolutionredissolved in dichloromethane (100 mL)
  3. temperatureto warm to room temperature
  4. stirringstirred for 16 h
  5. extractionThe mixture was extracted with aqueous hydrochloric acid (0.5N), water, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customaffording the crude product
  10. customPurification over silica gel (eluent: CH2Cl2/EtOAc)

출처 및 근거

ORD 기록
ord-b937993aad594f32a756884483cb982a
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09247740B2

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