Pyridine → HCID 118075554, compound

HRID 1051736Notes

Reaction equation

HRID 1051736 reaction equation
[CH2:1]([N:3]([CH2:6]C)CC)[CH3:2].[CH3:8][C@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[C:15]=2[O:19][CH2:20][CH2:21][CH3:22])[N:10]1[C:29](=[O:31])[CH3:30].ClC(Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl.N1C=CC=CC=1.C(N)C>ClCCl>[C:29]([N:10]1[C:11]2[C:16](=[C:15]([O:19][CH2:20][CH2:21][CH3:22])[C:14]([CH:23]3[CH2:28][CH2:27][N:26]([C:6]([NH:3][CH2:1][CH3:2])=[O:35])[CH2:25][CH2:24]3)=[CH:13][CH:12]=2)[CH2:17][CH2:18][C@@H:9]1[CH3:8])(=[O:31])[CH3:30]

Participants

7

Reactant 5

HCID 1049PyridineHCID 6341EthylamineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 118076148HCID 118076148, compound

Product 1

HCID 118075554HCID 118075554, compoundYield 186.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Triethylamine (0.05 mL, 0.35 mmol) was added to a solution of (S)-1-(2-methyl-6-(piperidin-4-yl)-5-propoxy-3,4-dihydroquinolin-1(2H)-yl)ethanone (20.0 mg, 0.06 mmol) in dichloromethane (5 mL). The reaction was cooled to 0° C. and triphosgene (6.3 mg, 0.02 mmol) dissolved in dichloromethane (3 mL) was added. The reaction mixture was warmed to room temperature and stirred for 3 hours. Pyridine (3 μL, 0.03 mmol) and ethylamine (2.7 mg, 0.06 mmol) were then added in sequence and the solution was stirred overnight. The reaction was quenched via the addition of water (5 mL) and 1 M citric acid (1 mL). The organic layer was collected and further washed with water (5 mL) and brine (5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified via column chromatography on silica gel (Biotage 10 g column, gradient elution with 0-5% methanol in ethyl acetate) to afford (S)-4-(1-acetyl-2-methyl-5-propoxy-1,2,3,4-tetrahydroquinolin-6-yl)-N-ethylpiperidine-1-carboxamide (15 mg, 61%) as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.97-1.05 (m, 6H), 1.15 (t, J=7.04 Hz, 3H), 1.18-1.27 (m, 1H), 1.37-1.53 (m, 2H), 1.63 (br d, J=11.73 Hz, 2H), 1.69-1.78 (m, 2H), 2.02 (s, 3H), 2.15-2.30 (m, 2H), 2.63-2.79 (m, 3H), 2.90-3.07 (m, 3H), 3.60-3.75 (m, 2H), 4.07 (br d, J=16.12 Hz, 2H), 4.50-4.62 (m, 1H), 6.45 (br t, J=5.42 Hz, 1H), 7.03 (br s, 2H). MS (ESI, pos. ion) m/z 402 [M+H]+.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was warmed to room temperature
  3. stirringthe solution was stirred overnight
  4. customThe reaction was quenched via the addition of water (5 mL) and 1 M citric acid (1 mL)
  5. customThe organic layer was collected
  6. washfurther washed with water (5 mL) and brine (5 mL)
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified via column chromatography on silica gel (Biotage 10 g column, gradient elution with 0-5% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-68e56d3934e54631bd715eb0526e2e5d
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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