Hydrogen Bromide → HCID 123471154, compound

HRID 1509150Notes

Reaction equation

HRID 1509150 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:41]=[N:42][CH:43]=[CH:44][CH:45]=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:41]=[N:42][CH:43]=[CH:44][CH: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

7

Reactant 5

HCID 260Hydrogen BromideHCID 24758Sodium hydrideHCID 2459343-(Bromomethyl)pyridineHCID 516892Sodium BicarbonateHCID 67256382HCID 67256382, compound

Product 1

HCID 123471154HCID 123471154, compoundYield 38%

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 (51 mg, 0.11 mmol) in dry DMF (1 ml) was added sodium hydride (11 mg, 0.26 mmol) and 3-(bromomethyl)pyridine.HBr (33 mg, 0.13 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 80% EtOAc in cyclohexane) to give the title compound (23 mg, 38%). 1H NMR (500 MHz, CDCl3): 8.60-8.50 (2H, br s), 7.60 (2H, d), 7.28 (1H, s), 7.19-7.15 (6H, m), 7.12 (1H, s), 6.97 (2H, d), 5.13 (2H, s), 4.93 (3H, 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 80% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-2f7fb7ab4e454f4f8c3686b674044608
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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