Iodoethane → HCID 86683582, compound

HRID 1509160Notes

Reaction equation

HRID 1509160 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.[H-].[Na+].I[CH2:39][CH3:40]>CN(C)C=O>[CH2:39]([N:3]1[C:2](=[O: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]([CH3:32])([CH3:34])[CH3:33])[CH2:25][CH2:26][CH2:27]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][C:4]1=2)[CH3:40]

Participants

5

Reactant 3

HCID 6340Iodoethane2×HCID 24758Sodium hydride2×HCID 67256382HCID 67256382, compound

Product 1

HCID 86683582HCID 86683582, compoundYield 13.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °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) in anhydrous N,N-dimethylformamide (1 mL) to give a yellow solution, then cooled to 0° C. under a nitrogen atmosphere. Sodium hydride, 60% in oil (10 mg, 0.254 mmol) was added and the mixture stirred at 0° C. for 15 minutes. Iodoethane (10 μl, 0.127 mmol) was added and the mixture stirred at 0° C. for 30 minutes, allowed to warm to room temperature then stirred for one hour. Further sodium hydride, 60% in oil (10.18 mg, 0.254 mmol) was added and the reaction mixture was heated to 40° C. under a nitrogen atmosphere for one hour. Further iodoethane (10 μl, 0.127 mmol) was added and the mixture stirred at room temperature for 30 minutes. The reaction mixture was quenched by the addition of saturated sodium bicarbonate solution (5 mL) and extracted into ethyl acetate (3×5 mL). The organic phase was washed with 50:50 water:brine (2×10 mL) then brine (10 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 88:12 to 0:100) to give the desired product as a pale yellow solid (7 mg, 13% yield). 1H-NMR (500 MHz, CDCl3) δ 7.10-7.28 (10H, m), 4.93 (1H, br s), 4.81 (2H, s), 3.94 (2H, q), 2.10-2.55 (4H, m), 1.90-2.08 (1H, m), 1.65-1.80 (1H, m), 1.00-1.40 (9H, br m), 1.14 (3H, t). LCMS (Method A) RT=7.29 min, M+H+=500.12.

Workup

  1. customIn a 15 mL reaction tube
  2. customto give a yellow solution
  3. stirringthe mixture stirred at 0° C. for 30 minutes
  4. temperatureto warm to room temperature
  5. stirringthen stirred for one hour
  6. temperaturethe reaction mixture was heated to 40° C. under a nitrogen atmosphere for one hour
  7. stirringthe mixture stirred at room temperature for 30 minutes
  8. customThe reaction mixture was quenched by the addition of saturated sodium bicarbonate solution (5 mL)
  9. extractionextracted into ethyl acetate (3×5 mL)
  10. washThe organic phase was washed with 50:50 water
  11. dry with materialbrine (2×10 mL) then brine (10 mL), dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to dryness under reduced pressure
  14. customThe residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 88:12 to 0:100)

Sources & evidence

ORD record
ord-b1e5f0f763e14b2080fd7f0933598be7
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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