Pyridine → N-(6-bromo-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxamide

HRID 1506480노트

반응식

HRID 1506480 반응식
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]([OH:18])=O)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.Cl.[NH2:26][CH:27]1[CH2:36][CH2:35][C:34]2[C:29](=[CH:30][CH:31]=[C:32]([Br:37])[CH:33]=2)[C:28]1=[O:38].C(N(C(C)C)CC)(C)C>ClCCl.N1C(F)=NC(F)=NC=1F>[Br:37][C:32]1[CH:33]=[C:34]2[C:29](=[CH:30][CH:31]=1)[C:28](=[O:38])[CH:27]([NH:26][C:16]([C:10]1[O:9][N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:11]=1[C:12]([F:13])([F:14])[F:15])=[O:18])[CH2:36][CH2:35]2

참가 물질

7

반응물 4

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 583740941236188-80-9HCID 671707672-amino-6-bromo-3,4-dihydronaphthalen-1(2H)-one hydrochloride

생성물 1

HCID 67167732N-(6-bromo-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxamide수율 73.9%

시약·촉매·용매 2

HCID 12664Cyanuric fluoride촉매HCID 6344Dichloromethane용매3회

실험 절차

To 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylic acid (Intermediate I-3D, 0.465 g, 1.808 mmol) in dichloromethane (5 mL) was added pyridine (0.175 ml, 2.170 mmol) followed by cyanuric fluoride (0.188 ml, 2.172 μmol) at room temperature. The reaction mixture was stirred at room temperature for 20 h., and partitioned between dichloromethane (30 mL) and cold 0.5N HCl (15 mL). The dichloromethane layer was separated, dried over sodium sulfate, and concentrated to afford an orange-red solid. The solid was dissolved in dichloromethane (5 mL) and added dropwise over a period of 2 min. to 2-amino-6-bromo-3,4-dihydronaphthalen-1(2H)-one hydrochloride (Preparation 82B, 0.5 g, 1.808 mmol) in dichloromethane (5.00 mL) and diisopropylethylamine (0.789 ml, 4.52 mmol) at 0° C. The reaction mixture was allowed to come to room temperature over a period of 20 min., stirred at room temperature for 2 h., and partitioned between dichloromethane (30 mL) and cold 0.5N HCl (10 mL). The dichloromethane layer was separated, dried over sodium sulfate, and concentrated. The resulting solid was triturated with ether (15 mL), sonicated for 5 min. and filtered to yield N-(6-bromo-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxamide (0.640 g, 1.335 mmol, 73.9% yield) as a light tan solid. LC/MS M+1=480.

후처리

  1. custompartitioned between dichloromethane (30 mL) and cold 0.5N HCl (15 mL)
  2. customThe dichloromethane layer was separated
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customto afford an orange-red solid
  6. waitto come to room temperature over a period of 20 min.
  7. stirringstirred at room temperature for 2 h.
  8. custompartitioned between dichloromethane (30 mL) and cold 0.5N HCl (10 mL)
  9. customThe dichloromethane layer was separated
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. customThe resulting solid was triturated with ether (15 mL)
  13. customsonicated for 5 min.
  14. filtrationfiltered

출처 및 근거

ORD 기록
ord-0ff764cd656f488f838d298b62073c67
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216972B2

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