Propargyl bromide → HCID 131734401, compound

HRID 1509126Notes

Reaction equation

HRID 1509126 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+].[CH2:38](Br)[C:39]#[CH:40].[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]([CH2:40][C:39]#[CH:38])[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 7842Propargyl bromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67256382HCID 67256382, compound

Product 1

HCID 131734401HCID 131734401, compoundYield 68%

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 (23 mg, 0.05 mmol) in dry DMF (1 mL) was added sodium hydride (3 mg, 0.05 mmol) at 0° C. under nitrogen. After 1 h at 0° C., propargyl bromide (16 μL, 0.15 mmol) was added and the resulting mixture was stirred for an additional 1 h 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 30% EtOAc in cyclohexane) to give the title compound (17 mg, 68%). 1H NMR (500 MHz, CDCl3): 7.50 (1H, s), 7.31-7.24 (7H, m), 7.22-7.20 (2H,m), 5.01 (1H, br s), 4.92 (2H, s), 4.73 (2H, d), 2.55-2.25 (4H, m), 2.32 (1H, t), 2.09-2.01 (1H, m), 1.85-1.76 (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 silica gel chromatography (gradient 0 to 30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-4b496611ec1642fb83b601c6c27593f7
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…