Water → HCID 69654478, compound

HRID 1244014Notes

Reaction equation

HRID 1244014 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][N:17]([CH2:21][CH:22]3[CH2:26][CH2:25][C:24](=[O:27])[NH:23]3)[C@H:16]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[N:9]([CH3:34])[C:8](=[O:35])[CH2:7][CH2:6]2.[H-].[Na+].[CH3:38]I.O>C1COCC1>[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]([CH2:21][C@@H:22]3[CH2:26][CH2:25][C:24](=[O:27])[N:23]3[CH3:38])[C@H:16]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[N:9]([CH3:34])[C:8](=[O:35])[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 69654964HCID 69654964, compound

Product 1

HCID 69654478HCID 69654478, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 6-Methoxy-1-methyl-7-{[1-(5-oxo-pyrrolidin-2-ylmethyl)-(2S,3S)-2-phenyl-piperidin-3-ylamino]-methyl}-3,4-dihydro-1H-quinolin-2-one (194 mg, 0.408 mmol) in 5 mL of THF at room temperature was added 18 mg (0.448 mmol) of 60% sodium hydride suspended in mineral oil and stirred for 20 minutes. Methyl iodide (0.028 mL, 0.448 mmol) was then added and stirred for 1 hour 18 mg (0.448 mmol) of 60% sodium hydride suspended in mineral oil was added and stirred overnight. A small amount of water was added and the solvent was removed under vacuum. The residue was dissolved in ethyl acetate, washed twice with water, dried over MgSO4, filtered, and concentrated. Silica gel chromatography using (95:5 ethyl acetate/methanol) as the eluent gave 25 mg (13%) of the title compound, a pale yellow oil. Rf=0.07 (9:1 ethyl acetate/methanol). MS (M+H)+=491.2; 1H NMR (400 MHz, CDCl3): δ 1.42–1.60 (m, 3H), 1.84–1.88 (dd, J=13.4 Hz, 4.8 Hz, 1H), 2.01–2.14 (m, 5H), 2.17–2.24 (m, 2H), 2.54–2.57 (t, J=7.3 Hz, 3H), 2.67–2.73 (m, 1H), 2.76–2.78 (t, J=7.3 Hz, 2H), 2.88 (s, 3H), 3.13 (s, 3H), 3.21–3.24 (d, J=10.9 Hz, 1H), 3.32–3.33 (d, J=3.0 Hz, 1H), 3.36–3.40 (d, J=14.3 Hz, 1H), 3.56 (s, 3H), 3.61–3.68 (m, 2H), 6.49 (s, 1H), 6.65 (s, 1H), 7.18–7.34 (m, 5H). 13C NMR (100 MHz, CDCl3): δ 20.4, 23.9, 25.5, 27.5, 29.6, 31.8, 45.4, 54.2, 55.5, 56.3, 58.0, 59.9, 72.7, 109.9, 116.0, 127.1, 128.1, 129.0, 133.6, 140.9, 152.8, 170.0, 175.0. 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. additionwas added
  2. stirringstirred overnight
  3. customthe solvent was removed under vacuum
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed twice with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f6ee930cb7b642e3b4e84e572cd95e48
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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