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

HRID 1025886노트

반응식

HRID 1025886 반응식
[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:3]=1[O:4][C:5]1[C:10]([C:11]([O-:13])=O)=[CH:9][N:8]=[C:7]([CH3:14])[CH:6]=1.[Li+].C(N(C(C)C)C(C)C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[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>[CH:54]1([N:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[N:60]([C:11]([C:10]3[CH:9]=[N:8][C:7]([CH3:14])=[CH:6][C:5]=3[O:4][C:3]3[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:2]=3[Cl:1])=[O:13])[CH2:59][CH2:58]2)[CH2:56][CH2:55]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 67320585Lithium 4-(2,5-dichloro-phenoxy)-6-methyl-nicotinateHCID 673207551-Cyclopropyl-1,2,3,4-tetrahydroquinoxaline

생성물 1

HCID 53259032(4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-[4-(2,5-dichloro-phenoxy)-6-methyl-pyridin-3-yl]-methanone수율 60%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 420 mg (1.381 mmol) lithium 4-(2,5-dichloro-phenoxy)-6-methyl-nicotinate in 6 mL dry N,N-dimethylformamide was added 1.17 mL (6.907 mmol) N-ethyldiisopropylamine and 635 mg (1.658 mmol) O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 289 mg (1.658 mmol) 1-cyclopropyl-1,2,3,4-tetrahydro-quinoxaline (Example 8, intermedaite a). The reaction mixture was stirred for 18 hours at room temperature and then poured on 30 mL 10% aqueous sodium bicarbonate solution and 30 mL ethyl acetate. The layers were separated and the aqueous layer was extracted a second time with 30 mL ethyl acetate. The 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 gradient of n-heptane:ethyl acetate (100:0 to 0:100) to give 375 mg (60%) of the title compound as a light yellow solid. MS (ESI): m/z=454.108 [M+H]+.

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted a second time with 30 mL ethyl acetate
  3. washThe 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-dabe2e80b1774278b65840fb1ae15271
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08729091B2

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