Sodium hydride → HCID 123692355, compound

HRID 1509158Notes

Reaction equation

HRID 1509158 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+].Br[CH2:39][CH2:40][O:41][CH3:42].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]([CH2:39][CH2:40][O:41][CH3:42])[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 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 516892Sodium BicarbonateHCID 67256382HCID 67256382, compound

Product 1

HCID 123692355HCID 123692355, compoundYield 18.9%

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 (48 mg, 0.10 mmol) in dry DMF (1 mL) was added sodium hydride (16 mg, 0.41 mmol) and 1-bromo-2-methoxyethane (28 mg, 0.20 mmol) under nitrogen. The resulting mixture was stirred for 2 hours at 80° C. A saturated solution of NaHCO3 was added and the mixture was extracted with dichloromethane (3×10 ml) 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 40% EtOAc in cyclohexane) to give the title compound (10 mg, 18%). 1H NMR (500 MHz, CDCl3): 7.49 (1H, s), 7.23-7.17 (7H, m), 7.12-7.11 (2H, m), 4.95 (1H, s), 4.82 (2H, s), 4.05 (2H, t), 3.61 (2H, t), 3.29 (3H, s), 2.52-2.20 (4H, m), 2.00-1.95 (1H, m), 1.79-1.65 (1H, m), 1.40-1.10 (9H, br).

Workup

  1. extractionthe mixture was extracted with dichloromethane (3×10 ml)
  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 40% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-3d0e59cb84fb42c393e6b8d2c2ded696
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…