Dimethylamine → 6-Chloro-2-(3-dimethylaminocyclopentyl)-quinoline-5-carboxylic acid (4,4-difluoro-1-hydroxy-cyclohexyl methyl)-amide

HRID 1056788Notes

Reaction equation

HRID 1056788 reaction equation
[F:1][C:2]1([F:30])[CH2:7][CH2:6][C:5]([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17]([CH:24]4[CH2:28][CH2:27][C:26](=O)[CH2:25]4)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])([OH:8])[CH2:4][CH2:3]1.C[CH2:32][N:33](CC)[CH2:34]C.CNC.C1COCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[F:30][C:2]1([F:1])[CH2:3][CH2:4][C:5]([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17]([CH:24]4[CH2:28][CH2:27][CH:26]([N:33]([CH3:34])[CH3:32])[CH2:25]4)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])([OH:8])[CH2:6][CH2:7]1

Participants

7

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 1185666266-Chloro-2-(3-oxo-cyclopentyl)-quinoline-5-carboxylic acid (4,4-difluoro-1-hydroxy-cyclohexylmethyl)-amide

Product 1

HCID 1185666936-Chloro-2-(3-dimethylaminocyclopentyl)-quinoline-5-carboxylic acid (4,4-difluoro-1-hydroxy-cyclohexyl methyl)-amideYield 22.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 6-chloro-2-(3-oxo-cyclopentyl)-quinoline-5-carboxylic acid (4,4-difluoro-1-hydroxycyclohexylmethyl)-amide (0.30 g, 0.28 mmol, 1.00 eq) in DCM (15.00 ml, 50.00 V) were added Et3N (0.09 g, 0.84 mmol, 3.00 eq) and dimethylamine solution 2.0 M in THF (0.70 mL, 1.40 mmol, 5.00 eq) at 0° C., and warmed to room temperature. The reaction mixture was stirred at RT for 1 h and sodium triacetoxyborohydride (0.09 g, 0.42 mmol, 1.50 eq) was added and the reaction mixture was stirred at RT for 16 h and the solvent was removed under vacuum. The crude product was purified by prep HPLC to provide 6-chloro-2-(3-dimethylaminocyclopentyl)-quinoline-5-carboxylic acid (4,4-difluoro-1-hydroxy-cyclohexyl methyl)-amide (0.03 g, 0.06 mmol, 22.3%, Brown solid). 1H NMR (400 MHz, DMSO-d6): δ 8.81 (t, J=5.82 Hz, 1H), 8.01-7.96 (m, 2H), 7.76-7.74 (m, 1H), 7.60-7.56 (m, 1H), 7.56-3.28 (m, 1H), 3.27-3.25 (m, 2H), 2.68-2.57 (m, 1H), 2.56-2.48 (m, 1H), 2.25-2.16 (m, 1H), 2.15-2.07 (m, 6H), 2.06-1.96 (m, 5H), 1.96-1.90 (m, 4H), 1.88-1.83 (m, 2H), 1.78-1.72 (m, 1H), 1.30-1.24 (m, 2H). m/z: 450.2 [M+H]+

Workup

  1. stirringthe reaction mixture was stirred at RT for 16 h
  2. customthe solvent was removed under vacuum
  3. customThe crude product was purified by prep HPLC

Sources & evidence

ORD record
ord-32185ca9ef774b4ca1c0246af65d7d15
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

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