Potassium Carbonate → tert-butyl(1-(4-(1-((3-methyloxetan-3-yl)methyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate

HRID 1509260Notes

Reaction equation

HRID 1509260 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].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:43][C:44]1([CH3:48])[CH2:47][O:46][CH2:45]1.C([O-])(O)=O.[Na+]>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]([CH2:43][C:44]5([CH3:48])[CH2:47][O:46][CH2:45]5)[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 11430Potassium CarbonateHCID 791123-(Chloromethyl)-3-methyloxetaneHCID 516892Sodium BicarbonateHCID 67256382HCID 67256382, compound

Product 1

HCID 123395621tert-butyl(1-(4-(1-((3-methyloxetan-3-yl)methyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamateYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °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 (50 mg, 0.11 mmol) in dry DMF (1 mL) was added potassium carbonate (44 mg, 0.32 mmol) and 3-(chloromethyl)-3-methyloxetane (38 mg, 0.32 mmol) under nitrogen. The resulting mixture was stirred for 2.5 hours at 80° C. A saturated solution of NaHCO3 was added and the mixture was extracted with AcOEt (3×). The combined organic phases were dried over Na2SO4 and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 40% EtOAc in cyclohexane) to give the title compound (21 mg, 36%). 1H NMR (500 MHz, CDCl3): 7.23-7.17 (8H, m), 7.09-7.07 (2H, m), 4.94 (2H, s), 4.83 (2H, s), 4.64 (2H, d), 4.23 (2H, d), 4.05 (2H, s), 2.52-2.20 (4H, m), 2.00-1.95 (1H, m), 1.79-1.65 (1H, m), 1.36 (3H, s), 1.40-1.10 (9H, br).

Workup

  1. extractionthe mixture was extracted with AcOEt (3×)
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. concentrationconcentrated to dryness under reduced pressure
  4. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 40% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-54b343dc8c3e404a90596621cfd5eae8
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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