Bromocyclopentane → HCID 86683589, compound

HRID 1509172Notes

Reaction equation

HRID 1509172 reaction equation
[O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:11][C:4]=2[NH:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH:43]1[CH2:47][CH2:46][CH2:45][CH2:44]1>CN(C)C=O.C(=O)(O)[O-].[Na+]>[CH:43]1([N:3]2[C:2](=[O:1])[CH2:7][O:6][C:5]3[N:8]=[C:9]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH2:25][CH2:26][CH2:27]5)=[CH:20][CH:19]=4)[C:10]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[CH:11][C:4]2=3)[CH2:47][CH2:46][CH2:45][CH2:44]1

Participants

6

Reactant 3

HCID 8728BromocyclopentaneHCID 11430Potassium CarbonateHCID 67256382HCID 67256382, compound

Product 1

HCID 86683589HCID 86683589, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

In a 15 mL reaction tube was added tert-butyl 1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (50 mg, 0.106 mmol), potassium carbonate (44 mg, 0.318 mmol) and bromocyclopentane (0.034 mL, 0.318 mmol) in anhydrous N,N-dimethylformamide (1 mL) to give an orange suspension. The reaction mixture was stirred at 80° C. for one hour. The reaction mixture was allowed to cool to room temperature, diluted with saturated sodium bicarbonate solution (5 mL) and extracted into dichloromethane (3×3 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give a yellow oil. This was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 20:80) to give the desired product as an off-white solid (12 mg, 21% yield). 1H-NMR (500 MHz, CDCl3) δ 7.32 (1H, s), 7.17-7.28 (7H, m), 7.10-717 (2H, m), 4.94 (1H, br s), 4.83 (1H, quin), 4.72 (2H, s), 2.05-2.60 (6H, m), 1.83-2.03 (5H, m), 1.54-1.82 (3H, m), 1.00-1.45 (9H, br m). LCMS (Method A) RT=8.25 min, M+H+=540.19.

Workup

  1. customIn a 15 mL reaction tube
  2. customto give an orange suspension
  3. temperatureto cool to room temperature
  4. extractionextracted into dichloromethane (3×3 mL)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customto give a yellow oil
  9. customThis was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 20:80)

Sources & evidence

ORD record
ord-1b5fb0487bf643f5bd85e2b7bdd1e315
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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