1-Propanol → 6-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-1-propyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-one

HRID 1244005Notes

Reaction equation

HRID 1244005 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH2:13][NH:14][C@H:15]1[CH2:20][CH2:19][CH2:18][NH:17][C@H:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[N:9]([CH3:27])[C:8](=[O:28])[CH2:7][CH2:6]2.I.CSC1NCCN=1.[CH2:37](O)[CH2:38][CH3:39]>C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH2:13][NH:14][C@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([CH2:37][CH2:38][CH3:39])[C@H:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[N:9]([CH3:27])[C:8](=[O:28])[CH2:7][CH2:6]2

Participants

5

Reactant 3

HCID 10311-PropanolHCID 103093706-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-oneHCID 122212281H-Imidazole, 4,5-dihydro-2-(methylthio)-, hydriodide (1:1)

Product 1

HCID 696548736-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-1-propyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-oneYield 21%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-Imidazolidinethione (10 g, 97.89 mmol) and methyl iodide (6.70 mL, 107.67 mmol) were stirred in 20 mL of absolute ethanol at reflux for 2 hours. The reaction was cooled and an equal volume of diethyl ether was added. The suspension was filtered to give 22.9 g (96%) of 2-methylsulfanyl-4,5-dihydro-1H-imidazole hydrogen iodide as an off-white solid that was used in the next reaction. 6-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-one (500 mg, 1.32 mmol) and 2-methylsulfanyl-4,5-dihydro-1H-imidazole hydrogen iodide (402 mg, 1.65 mmol) were stirred in 5 mL of n-propanol at reflux for 2 days. The reaction was diluted with ethyl acetate, washed 1× with satd. K2CO3, dried over MgSO4, filtered, and concentrated. Silica gel chromatography using (95:5 ethyl acetate/methanol) gave 123 mg (21%) of the title compound, a pale yellow oil. Rf=0.12 (9:1 ethyl acetate/methanol). 1H NMR (400 MHz, CDCl3): δ 0.67–0.70 (t, J=7.4 Hz, 3H), 1.36–1.49 (m, 4H), 1.72–1.79 (m, 1H), 1.92–2.04 (m, 3H), 2.39–2.43 (m, 1H), 2.51–2.55 (t, J=7.3 Hz, 2H), 2.63 (s, 1H), 2.73–2.78 (t, J=7.3 Hz, 2H), 3.12 (s, 3H), 3.16–3.19 (m, 1H), 3.30 (s, 1H), 3.34–3.38 (d, J=14.4 Hz, 1H), 3.49 (s, 3H), 3.60–3.64 (d, J=14.4 Hz, 1H), 6.46 (s, 1H), 6.60 (s, 1H), 7.15–7.32 (m, 5H). 13C NMR (100 MHz, CDCl3): δ 11.8, 19.3, 20.3, 25.4, 27.5, 29.5, 31.7, 45.1, 53.4, 55.4, 56.2, 57.9, 72.1, 109.7, 115.9, 124.8, 126.5, 127.7, 128.7, 133.3, 141.7, 152.8, 169.9. The dihydrochloride salt was prepared by the addition of 2 M HCl in ether to a solution of the product in ethyl acetate. Concentration gave a white solid.

Workup

  1. customwas used in the next reaction
  2. temperatureat reflux for 2 days
  3. washwashed 1× with satd
  4. dry with materialK2CO3, dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-579b4abdb18b43b7944f3a3c4b6578a8
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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