Hydrogen Bromide → HCID 123503375, compound

HRID 1509168Notes

Reaction equation

HRID 1509168 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][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=1.Br.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][C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=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

7

Reactant 5

HCID 260Hydrogen BromideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 5642092-(Bromomethyl)pyridineHCID 67256382HCID 67256382, compound

Product 1

HCID 123503375HCID 123503375, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 (75 mg, 0.16 mmol) in dry DMF (1 mL) was added sodium hydride (15 mg, 0.38 mmol) and 2-(bromomethyl)pyridine.HBr (48 mg, 0.19 mmol) under nitrogen. The resulting mixture was stirred for 1 hour at room temperature. 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 (11 mg, 12%). 1H NMR (500 MHz, CDCl3): 8.49 (1H, d), 7.63 (1H, t), 7.42 (1H, s), 7.27 (1H, d), 7.19-7.13 (8H, m), 7.01-6.98 (2H, d), 5.23 (2H, s), 4.92 (2H, s), 4.91 (1H, s), 2.52-2.20 (4H, m), 2.00-1.95 (1H, m), 1.75-1.70 (1H, m), 1.44-1.15 (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-5dd9d8dce3104c7483a5366e9a26f1b1
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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