Methyl iodide → Tert-butyl(1-(4-(6-methyl-5-oxo-3-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamate

HRID 1509106Notes

Reaction equation

HRID 1509106 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:24](=[O:34])[NH:23][CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:39].[NH4+].[Cl-]>CN(C=O)C>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:27]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:26][C:25]4[C:24](=[O:34])[N:23]([CH3:39])[CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 124023320Tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 123223204Tert-butyl(1-(4-(6-methyl-5-oxo-3-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamateYield 75.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamate (30 mg, 0.06 mmol) in dry DMF (1 mL) was added sodium hydride (3 mg, 0.07 mmol) at 0° C. under nitrogen. After 1 h at 0° C., iodomethane (17 μL, 0.19 mmol) was added and the resulting mixture was stirred for an additional 10 min at 0° C. A saturated solution of NH4Cl was added and the mixture was extracted with dichloromethane (3×) using a phase separator (Isolute® SPE). The combined organic phases were concentrated to dryness under reduced pressure. The resulting residue was purified by silica gel chromatography (gradient 0 to 50% EtOAc in hexane) to give the title compound (22 mg, 71%). 1H NMR (500 MHz, CDCl3): 8.35 (1H, s), 7.34 (2H, d), 7.29 (2H,d), 7.24-7.22 (3H, m), 7.19-7.17 (2H, m), 5.06 (1H, br s), 3.70 (2H, t), 3.29 (2H, t), 3.19 (3H, s), 2.54-2.30 (4H, m), 2.08-2.00 (1H, m), 1.83-1.74 (1H, m), 1.44-1.18 (9H, br).

Workup

  1. extractionthe mixture was extracted with dichloromethane (3×)
  2. concentrationThe combined organic phases were concentrated to dryness under reduced pressure
  3. customThe resulting residue was purified by silica gel chromatography (gradient 0 to 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-42071d7c562b437696f46a662dc234fb
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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