Diisopropylethylamine → 1-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid methyl ester

HRID 1877409Notes

Reaction equation

HRID 1877409 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:3]=1[O:4][C:5]1[N:13]=[CH:12][C:11]([F:14])=[CH:10][C:6]=1[C:7](Cl)=[O:8].C(N(C(C)C)C(C)C)C.[CH3:29][O:30][C:31]([CH:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH2:35][CH2:34]1)=[O:32]>CN(C=O)C>[CH3:29][O:30][C:31]([CH:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[N:36]([C:7]([C:6]2[C:5]([O:4][C:3]3[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:2]=3[Cl:1])=[N:13][CH:12]=[C:11]([F:14])[CH:10]=2)=[O:8])[CH2:35][CH2:34]1)=[O:32]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10631570Methyl 1,2,3,4-tetrahydroquinoline-4-carboxylateHCID 866412572-(2,5-Dichloro-phenoxy)-5-fluoro-nicotinoyl chloride

Product 1

HCID 592944731-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid methyl esterYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2,5-dichloro-phenoxy)-5-fluoro-nicotinoyl chloride (48.1 mg, 0.15 mmol, 1.0 equiv; Example 146, Step 1) in anhydrous DMF (1 mL) was added N-ethyldiisopropylamine (97 mg, 128 μL, 0.75 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and 1,2,3,4-tetrahydro-quinoline-4-carboxylic acid methyl ester (31.6 mg, 0.165 mmol, 1.1 equiv; [CAS RN 68066-85-3]) and the reaction mixture stirred at rt for 2 h. 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 9.1 mg (13%) of the title compound as a light yellow solid. MS (ISP): 475.1 [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-94ddea00e3e84a47ac4e3effd90a27cb
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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