Sulfoxonium, trimethyl-, iodide (1:1) → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(1-phenylcyclopropyl)quinoline

HRID 1618678Notes

Reaction equation

HRID 1618678 reaction equation
[I-].C[S+](C)(C)=O.[CH3:7]C(C)([O-])C.[K+].[F:13][C:14]1[CH:23]=[C:22]([F:24])[CH:21]=[C:20]2[C:15]=1[C:16]([N:34]1[C:42]3[C:37](=[N:38][CH:39]=[C:40]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)[CH:41]=3)[C:36]([CH3:50])([CH3:49])[CH2:35]1)=[C:17]([CH3:33])[C:18]([C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[CH2:26])=[N:19]2>CS(C)=O.C1COCC1>[CH3:49][C:36]1([CH3:50])[C:37]2=[N:38][CH:39]=[C:40]([N:43]3[CH2:44][CH2:45][O:46][CH2:47][CH2:48]3)[CH:41]=[C:42]2[N:34]([C:16]2[C:15]3[C:20](=[CH:21][C:22]([F:24])=[CH:23][C:14]=3[F:13])[N:19]=[C:18]([C:25]3([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:7][CH2:26]3)[C:17]=2[CH3:33])[CH2:35]1

Participants

6

Reactant 3

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 50939861HCID 50939861, compound

Product 1

HCID 509395954-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(1-phenylcyclopropyl)quinoline

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of trimethylsulfoxonium iodide (29.6 mg, 0.135 mmol) in dry DMSO (0.3 mL) was treated with potassium tert-butoxide (1.0M in THF, 0.135 mL, 0.135 mmol) at rt under a N2 atmosphere. The resulting solution was stirred for 30 min. A solution of 4-(1-(5,7-difluoro-3-methyl-2-(1-phenylvinyl)quinolin-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (46 mg, 0.090 mmol) in dry THF (0.836 mL) was added dropwise to the stirring solution, and the reaction was stirred for 3 h. The reaction was then quenched with 1N HCl, and the product extracted twice with EtOAc. The organic phase was dried over MgSO4 and concentrated under reduced pressure to give a crude residue that was purified by reverse-phase HPLC (0-80% acetonitrile in water) to give 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(1-phenylcyclopropyl)quinoline. 1H NMR (400 MHz, chloroform-d) δ ppm 7.62-7.73 (1H, m), 7.49-7.53 (1H, m), 7.19-7.25 (2H, m), 7.12-7.19 (1H, m), 7.03-7.11 (2H, m), 6.98 (1H, ddd, J=11.8, 8.9, 2.5 Hz), 5.51-5.55 (1H, m), 3.80-3.89 (1H, m), 3.68-3.80 (4H, m), 3.51-3.61 (1H, m), 2.86-2.97 (4H, m), 2.10-2.15 (3H, m), 1.71-1.79 (1H, m), 1.55-1.64 (2H, m), 1.49-1.54 (3H, m), 1.45-1.49 (1H, m), 1.41-1.45 (3H, m). Mass Spectrum (ESI) m/e=527.2 (M+1).

Workup

  1. stirringthe reaction was stirred for 3 h
  2. customThe reaction was then quenched with 1N HCl
  3. extractionthe product extracted twice with EtOAc
  4. dry with materialThe organic phase was dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customto give a crude residue that
  7. customwas purified by reverse-phase HPLC (0-80% acetonitrile in water)

Sources & evidence

ORD record
ord-eff4f959274042398bb5a9a7af8d20a2
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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