Potassium Carbonate → HCID 86719501, compound

HRID 1772264Notes

Reaction equation

HRID 1772264 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:7]=2.C(=O)([O-])[O-].[K+].[K+].Cl.[N+:24]([C:27]1[CH:32]=[CH:31][C:30]([NH:33][CH:34]2[CH2:39][CH2:38][CH:37]([O:40][CH2:41][C:42]([N:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)=[O:43])[CH2:36][CH2:35]2)=[CH:29][C:28]=1[C:50]([F:53])([F:52])[F:51])([O-:26])=[O:25]>CN(C=O)C.CCOC(C)=O>[N+:24]([C:27]1[CH:32]=[CH:31][C:30]([NH:33][CH:34]2[CH2:35][CH2:36][CH:37]([O:40][CH2:41][C:42]([N:44]3[CH2:49][CH2:48][N:47]([CH2:2][C:3]4[CH:4]=[N:5][C:6]5[C:11]([CH:12]=4)=[CH:10][CH:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:7]=5)[CH2:46][CH2:45]3)=[O:43])[CH2:38][CH2:39]2)=[CH:29][C:28]=1[C:50]([F:53])([F:52])[F:51])([O-:26])=[O:25]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 86719502HCID 86719502, compoundHCID 86719503HCID 86719503, compound

Product 1

HCID 86719501HCID 86719501, compoundYield 34.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-chloromethyl-7-trifluoromethyl-quinoline (140 mg, 0.57 mmol, 1.1 eq.) in DMF (10 ml) was added potassium carbonate (345 mg, 2.5 mmol, 5 eq.) then 2-[4-(4-Nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-1-piperazin-1-yl-ethanone hydrochloride (233 mg, 0.5 mmol, 1 eq.) was added. The solution was stirred overnight at 70° C. and diluted with EtOAc (25 ml) and washed with water (25 ml), saturated aqueous lithium chloride (25 ml) and brine (25 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue, which was applied onto a silica gel column and eluted with methanol in dichloromethane. The semi-purified material was further purified by HPLC to afford 2-[4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-1-[4-(7-trifluoromethyl-quinolin-3-ylmethyl)-piperazin-1-yl]-ethanone as a yellow solid (111.2 mg, 30%). (CI, m/z): [M+H]+ 640; 1H NMR (400 MHz, CDCl3): δ 1.20-1.36 (m, 2H), 1.40-1.54 (m, 2H), 2.08-2.21 (m, 4H), 2.46-2.61 (m, 4H), 3.32-3.49 (m, 2H), 3.53-3.62 (m, 2H), 3.63-3.71 (m, 2H), 3.76 (s, 2H), 4.20 (s, 2H), 4.46 (d, J=7.6 Hz, 1H), 6.63 (dd, J=9.1, 2.6 Hz, 1H), 6.85 (d, J=2.5 Hz, 1H), 7.75 (dd, J=8.5, 1.6 Hz, 1H) 7.94 (d, J=8.5 Hz, 1H), 8.02 (d, J=9.0 Hz, 1H), 8.13 (d, J=1.2 Hz, 1H), 8.43 (s, 1H), 9.03 (d, J=2.1 Hz, 1H).

Workup

  1. washwashed with water (25 ml), saturated aqueous lithium chloride (25 ml) and brine (25 ml)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto give a residue, which
  6. washeluted with methanol in dichloromethane
  7. customThe semi-purified material was further purified by HPLC

Sources & evidence

ORD record
ord-d19915b8277d4bc8825444067d6a9c00
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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