Triethylamine → (7-Chloro-3,4-dihydro-2H-quinolin-1-yl)-[2-(2,5-dichloro-phenoxy)-pyridin-3-yl]-methanone

HRID 1877355Notes

Reaction equation

HRID 1877355 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[N:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.Cl.[Cl:20][C:21]1[CH:30]=[C:29]2[C:24]([CH2:25][CH2:26][CH2:27][NH:28]2)=[CH:23][CH:22]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:20][C:21]1[CH:30]=[C:29]2[C:24]([CH2:25][CH2:26][CH2:27][N:28]2[C:7]([C:6]2[C:5]([O:4][C:3]3[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:2]=3[Cl:1])=[N:13][CH:12]=[CH:11][CH:10]=2)=[O:9])=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167959962-(2,5-Dichloro-phenoxy)-nicotinic acidHCID 447848337-Chloro-1,2,3,4-tetrahydroquinoline hydrochloride

Product 1

HCID 46194698(7-Chloro-3,4-dihydro-2H-quinolin-1-yl)-[2-(2,5-dichloro-phenoxy)-pyridin-3-yl]-methanoneYield 10%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (42.6 mg, 0.15 mmol, 1.0 equiv; Example 31, Step 1) in anhydrous DMF (1.5 mL) was added 7-chloro-1,2,3,4-tetrahydro-quinoline hydrochloride (33.7 mg, 0.17 mmol, 1.1 equiv; [CAS RN 90562-34-8]), triethylamine (30.4 mg, 42 μL, 0.3 mmol, 2.0 equiv; [CAS RN 121-44-8]) and HATU (62.7 mg, 0.17 mmol, 1.1 equiv; [CAS RN 148893-10-1]). The reaction mixture was heated by microwave irradiation to 110° C. for 30 min. 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 6 mg (10%) of the title compound. MS (ISP): 435.0 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-e9c90ce81802420e8f55e6fec64371e0
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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