1,2,3,4-Tetrahydroquinoline → [4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone

HRID 1966967

반응식

HRID 1966967 반응식
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[C:10]([C:11]([OH:13])=O)=[CH:9][N:8]=[CH:7][CH:6]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH:52]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH2:55][CH2:54][CH2:53]1>CN(C)C=O>[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][N:8]=[CH:9][C:10]=1[C:11]([N:52]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH2:55][CH2:54][CH2:53]1)=[O:13]

참가 물질

6

반응물 4

HCID 694601,2,3,4-TetrahydroquinolineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2회HCID 673204354-(2,5-Dichloro-phenoxy)-nicotinic acid

생성물 1

HCID 53311781[4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone수율 73%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 0.16 g (0.56 mmol) 4-(2,5-dichloro-phenoxy)-nicotinic acid in 3 mL N,N-dimethylformamide were added 0.225 g (0.59 mmol) O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 0.29 mL (1.69 mmol) N,N-diisopropylethylamine. To the light yellow solution 0.07 mL (0.59 mmol) 1,2,3,4-tetrahydroquinoline (commercially available; CAS RN 635-46-1) was added and the resulting light yellow solution was stirred at room temperature for 23 hours. The reaction mixture was poured on water and extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The resulting powder was purified by silica gel chromatography using a MPLC system (20 g silica gel column, CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50). The product-containing fractions were combined and evaporated to give 165 mg (73%) of the desired compound as a light brown solid. MS (ESI): m/z=399.06 [M+H]+.

후처리

  1. additionCAS RN 635-46-1) was added
  2. additionThe reaction mixture was poured on water
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. additiontreated with silica gel
  8. customevaporated
  9. customThe resulting powder was purified by silica gel chromatography
  10. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50)
  11. customevaporated

출처 및 근거

ORD 기록
ord-c5e598341b00460d876dd23c14f12766
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08420647B2

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