Methyl iodide → HCID 131734400, compound

HRID 1509124Notes

Reaction equation

HRID 1509124 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:19]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:20][C:21]4[NH:26][C:25](=[O:27])[CH2:24][O:23][C:22]=4[N:28]=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:19]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:20][C:21]4[N:26]([CH3:39])[C:25](=[O:27])[CH2:24][O:23][C:22]=4[N:28]=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 67256382HCID 67256382, compound

Product 1

HCID 131734400HCID 131734400, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl(1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (60 mg, 0.13 mmol) in dry DMF (1 mL) was added sodium hydride (6 mg, 0.14 mmol) at 0° C. under nitrogen. After 1 h at 0° C., iodomethane (9 μL, 0.14 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 Biotage silica gel chromatography (gradient 0 to 30% EtOAc in cyclohexane) to give the title compound as a white solid (38 mg, 60%). 1H NMR (500 MHz, CDCl3): 7.31-7.24 (8H, m), 721-7.19 (2H,m), 5.01 (1H, br s), 4.90 (2H, s), 3.39 (3H, s),2.55-2.25 (4H, m), 2.09-2.01 (1H, m), 1.84-1.76 (1H, m), 1.44-1.15 (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 Biotage silica gel chromatography (gradient 0 to 30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-08b579fac4264079b716ee4561d034ed
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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