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

HRID 1877421Notes

Reaction equation

HRID 1877421 reaction equation
[Br:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([O:6][C:7]2[N:15]=[CH:14][CH:13]=[CH:12][C:8]=2[C:9]([OH:11])=O)=[C:4]([Cl:19])[CH:3]=1.C(N(C(C)C)C(C)C)C.[I-].ClC1C=CC=C[N+]=1C.[NH:38]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH2:41][CH2:40][CH2:39]1>ClCCl>[Br:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([O:6][C:7]2[C:8]([C:9]([N:38]3[C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH2:41][CH2:40][CH2:39]3)=[O:11])=[CH:12][CH:13]=[CH:14][N:15]=2)=[C:4]([Cl:19])[CH:3]=1

Participants

6

Reactant 4

HCID 694601,2,3,4-TetrahydroquinolineHCID 81531DiisopropylethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 673686592-(4-Bromo-2,5-dichloro-phenoxy)-nicotinic acid

Product 1

HCID 59294540[2-(4-Bromo-2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanoneYield 61.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-bromo-2,5-dichloro-phenoxy)-nicotinic acid (50 mg, 0.14 mmol, 1.0 equiv; Example 163, Step 1) in anhydrous dichloromethane (1.5 mL) was added N-ethyldiisopropylamine (152 mg, 200 μL, 1.18 mmol, 8.4 equiv; [CAS RN 7087-68-5]) and 2-chloro-1-methylpyridinium iodide (42 mg, 0.17 mmol, 1.2 equiv; [CAS RN 14338-32-0]) and the reaction mixture stirred at rt. After 1 h, 1,2,3,4-tetrahydro-quinoline (22 mg, 21 μL, 0.17 mmol, 1.2 equiv; [CAS RN 635-46-1]) was added and stirring at rt continued over night. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 41 mg (61%) of the title compound as a white powder. MS (ISP): 476.9 [M+H]+.

Workup

  1. stirringstirring at rt
  2. waitcontinued over night
  3. customRemoval of the solvent mixture
  4. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  5. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  6. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-1cb2c3277a094372be617bf4ca922ef7
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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