Pyridine → (R)-2-Methyl-4-(3-trifluoromethyl-2-pyridyl)-N-(1-methyl-1,2,3,4-tetrahydro-quinolin-7-yl) piperazine-1-carboxamide

HRID 494227Notes

Reaction equation

HRID 494227 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][N:9]2[CH3:12])=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:20](OC1C=CC=CC=1)=[O:21].C(N(CC)CC)C.[CH3:36][C@@H:37]1[CH2:42][N:41]([C:43]2[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][CH:46]=[CH:45][N:44]=2)[CH2:40][CH2:39][NH:38]1>C(Cl)Cl>[CH3:36][C@@H:37]1[CH2:42][N:41]([C:43]2[C:48]([C:49]([F:52])([F:50])[F:51])=[CH:47][CH:46]=[CH:45][N:44]=2)[CH2:40][CH2:39][N:38]1[C:20]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][N:9]2[CH3:12])=[CH:4][CH:3]=1)=[O:21]

Participants

7

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 112174211-Methyl-1,2,3,4-tetrahydroquinolin-7-amineHCID 11528875(R)-3-Methyl-1-(3-(trifluoromethyl)pyridin-2-yl)piperazine

Product 1

HCID 57682689(R)-2-Methyl-4-(3-trifluoromethyl-2-pyridyl)-N-(1-methyl-1,2,3,4-tetrahydro-quinolin-7-yl) piperazine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 7-amino-1-methyl-1,2,3,4-tetrahydroquinoline (D3) (300 mg, 1.85 mmol) in DCM (5 ml) was added pyridine (164 ul, 2 mmol) followed by phenyl chloroformate (255 ul, 2 mmol) and the solution stirred at ambient temperature for 50 mins. Triethylamine (516 μl 3.7 mmol) was then added followed by a solution of (R)-2-methyl-4-(3-trifluoromethyl-2-pyridyl)piperazine (D22) (454 mg, 1.85 mmol) in DCM (5 ml) and the reaction stirred at ambient temperature until complete by tlc. The reaction mixture was washed (1M HCl, brine), dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash chromatography, eluting with an EtOAc/40-60° C. petroleum ether gradient, to give the title compound as a white solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.47 (dd, 1H), 7.90 (dd, 1H), 7.05 (dd, 1H), 6.84 (d, 1H), 6.78 (d, 1H), 6.49 (dd, 1H), 6.25 (br, 1H), 4.34 (m, 1H), 3.86 (m, 1H), 3.17-3.62 (m, 6H), 3.05 (m, 1H), 2.89 (s, 3H), 2.70.(t, 2H), 1.96 (m, 2H), 1.36 (d, 3H). MS (ES): MH+ 434.

Workup

  1. stirringthe reaction stirred at ambient temperature until complete by tlc
  2. washThe reaction mixture was washed (1M HCl, brine)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto give the crude product which
  6. customwas purified by flash chromatography
  7. washeluting with an EtOAc/40-60° C. petroleum ether gradient

Sources & evidence

ORD record
ord-f0c3c9c527be42f9baf232a948d117a0
Source dataset
uspto-grants-2009_05
Patent number
US07538121B2

Reaction notes

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