Diisopropylethylamine → 2-bromo-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide

HRID 1611940노트

반응식

HRID 1611940 반응식
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[CH3:44][O:45][C:46]1[C:51]2[N:52]=[C:53]([NH2:55])[O:54][C:50]=2[C:49]([CH:56]2[CH2:61][CH2:60][O:59][CH2:58][CH2:57]2)=[CH:48][CH:47]=1>C1COCC1.O1CCOCC1.CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH:55][C:53]1[O:54][C:50]2[C:49]([CH:56]3[CH2:57][CH2:58][O:59][CH2:60][CH2:61]3)=[CH:48][CH:47]=[C:46]([O:45][CH3:44])[C:51]=2[N:52]=1)=[O:7]

참가 물질

9

반응물 4

HCID 81531DiisopropylethylamineHCID 2227012-Bromoisonicotinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222522334-Methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-ylamine

생성물 1

HCID 222522322-bromo-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide수율 84.4%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 312751,4-Dioxane용매

실험 절차

To a stirred solution of 106 mg (0.52 mmol) 2-bromo-isonicotinic acid in 5 ml THF were added 230 mg (0.60 mmol) HATU and 0.10 ml (0.60 mmol) N-ethyldiisopropyl-amine and stirring continued at room temperature for 5 h. A solution of 100 mg (0.40 mmol) 4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-ylamine in 5 ml dioxane and 1 ml DMF was then added and stirring continued at 40° C. for 72 h. The reaction mixture was then poured into 100 ml water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (dichoromethane then methanol/dichloromethane 20/80) followed by trituration in ether afforded 146 mg (84%) 2-bromo-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide as a white crystalline solid. ES-MS m/e (%): 434 (M{81Br}+H+, 95), 432 (M{79Br}+H+, 100).

후처리

  1. stirringstirring
  2. waitcontinued at 40° C. for 72 h
  3. extractionextracted three times with ethyl acetate
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-f70d28d890fd4d42b970ff234391dcca
출처 데이터셋
uspto-grants-2006_01
특허 번호
US06992083B2

반응 노트

불러오는 중…