Diisopropylethylamine → [4-(4-Bromo-2,5-dichloro-phenoxy)-6-methyl-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

HRID 1967043노트

반응식

HRID 1967043 반응식
[Br:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([O:6][C:7]2[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=[C:9]([CH3:16])[CH:8]=2)=[C:4]([Cl:20])[CH:3]=1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:54]1([N:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[NH:60][CH2:59][CH2:58]2)[CH2:56][CH2:55]1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([O:6][C:7]2[CH:8]=[C:9]([CH3:16])[N:10]=[CH:11][C:12]=2[C:13]([N:60]2[C:61]3[C:66](=[CH:65][CH:64]=[CH:63][CH:62]=3)[N:57]([CH:54]3[CH2:56][CH2:55]3)[CH2:58][CH2:59]2)=[O:15])=[C:4]([Cl:20])[CH:3]=1

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2회HCID 673194804-(4-Bromo-2,5-dichloro-phenoxy)-6-methyl-nicotinic acidHCID 673207551-Cyclopropyl-1,2,3,4-tetrahydroquinoxaline

생성물 1

HCID 53311447[4-(4-Bromo-2,5-dichloro-phenoxy)-6-methyl-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone수율 23%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 0.17 g (0.451 mmol) 4-(4-bromo-2,5-dichloro-phenoxy)-6-methyl-nicotinic acid in 3 mL dry N,N-dimethylformamide was added 0.38 mL (2.225 mmol) N-ethyldiisopropylamine and 207 mg (0.541 mmol) 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 94 mg (0.541 mmol) 1-cyclopropyl-1,2,3,4-tetrahydro-quinoxaline (Example 8, intermediate a). The reaction mixture was stirred at room temperature for 18 hours and then poured on 30 mL 10% aqueous sodium bicarbonate solution and 30 mL ethyl acetate. The layers were separated. The aqueous layer was extracted with 30 mL ethyl acetate and the combined organic layers were washed with 30 mL brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (20 g silica gel column, CombiFlash Companion, Isco Inc.) with a gradient of n-heptane:ethyl acetate (100:0 to 40:60) to give 55 mg (23%) of the title compound as a light yellow solid. MS (ESI): m/z=534.018 [M+H]+.

후처리

  1. customThe layers were separated
  2. extractionThe aqueous layer was extracted with 30 mL ethyl acetate
  3. washthe combined organic layers were washed with 30 mL brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-4ed572f67dcc4fa88a5eccf5abc444a5
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08420647B2

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