Isopropyl iodide → 7-[(2S,3S)-(1-Isopropyl-2-phenyl-piperidin-3-ylamino)-methyl]-6-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one

HRID 1244010Notes

Reaction equation

HRID 1244010 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[CH:30]([CH3:32])[CH3:31]>C(#N)C.C(Cl)Cl>[CH:30]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:15]([NH:14][CH2:13][C:12]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][C:8](=[O:28])[N:9]3[CH3:27])=[CH:4][C:3]=2[O:2][CH3:1])[C@@H:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH3:32])[CH3:31]

Participants

5

Reactant 2

HCID 6362Isopropyl iodideHCID 103093706-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 696546317-[(2S,3S)-(1-Isopropyl-2-phenyl-piperidin-3-ylamino)-methyl]-6-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-oneYield 34.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

6-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-one (100 mg, 0.26 mmol) and 2-iodopropane (0.058 mL, 0.58 mmol) were stirred in acetonitrile at 60° C. for 2 days. The reaction was diluted with methylene chloride, washed once with satd. NaHCO3, dried over MgSO4, filtered, and concentrated. Silica gel chromatography using (9.1 ethyl acetate/methanol) gave 38 mg (34%) of the title compound, a yellow oil. Rf=0.08 (9:1 ethyl acetate/methanol). MS (M+H)+=422.1; 1H NMR (400 MHz, CDCl3): δ 0.66–0.68 (d, J=6.5 Hz, 3H), 1.00–1.02 (d, J=6.5 Hz, 3H), 1.35–1.42 (m, 1H), 1.50–1.53 (bd, J=13.0 Hz, 1H), 1.91–1.97 (m, 1H), 2.02–2.07 (m, 1H), 2.22–2.28 (t, J=11.5 Hz, 1H), 2.53–2.57 (t, J=7.4 Hz, 2H), 2.64 (s, 1H), 2.75–2.79 (t, J=7.4 Hz, 2H), 2.94–3.02 (m, 2H), 3.12 (s, 3H), 3.38–3.42 (d, J=14.6 Hz, 1H), 3.54 (s, 3H), 3.60 (s, 1H), 3.66–3.69 (d, J=14.6 Hz, 1H), 6.49 (s, 1H), 6.66 (s, 1H), 7.19–7.29 (m, 3H), 7.36–7.38 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 12.0, 20.3, 21.1, 25.5, 27.7, 29.6, 31.8, 44.1, 45.0, 48.5, 55.5, 56.3, 109.8, 112.8, 116.0, 124.9, 126.7, 127.8, 129.2, 133.5, 141.5, 152.9, 170.0. 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. washwashed once with satd
  2. dry with materialNaHCO3, dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-386d4262149b43d6ad9d3b206b054c6a
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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