Hydrochloric Acid → 3-[3-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)Phenyl]propynenitrile

HRID 1634975Notes

Reaction equation

HRID 1634975 reaction equation
[I-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:23]=[CH:22][C:14]3[NH:15][C:16](=[O:21])[O:17][C:18]([CH3:20])([CH3:19])[C:13]=3[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)#[CH:4].Cl[Si](C)(C)C.Cl.[C:30](#[N:32])C>O.CS(C)=O>[CH3:19][C:18]1([CH3:20])[O:17][C:16](=[O:21])[NH:15][C:14]2[CH:22]=[CH:23][C:11]([C:7]3[CH:6]=[C:5]([C:3]#[C:4][C:30]#[N:32])[CH:10]=[CH:9][CH:8]=3)=[CH:12][C:13]1=2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 6342AcetonitrileHCID 6397ChlorotrimethylsilaneHCID 98141916-(3-Ethynyl-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one

Product 1

HCID 98575553-[3-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)Phenyl]propynenitrileYield 4.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred mixture of DMSO, acetonitrile and water (9 mL/3 mL/0.5 mL) was added at rt under nitrogen cuprous cyanide (0.193 g, 2.2 mmol), sodium iodide (11 mg, 0.072 mmol), and 6-(3-ethynyl-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (0.2 g, 0.72 mmol). Chlorotrimethylsilane was then added to the above mixture in a dropwise manner. After addition, the mixture was heated at 50° C. for 72 hours. The reaction mixture was then cooled to rt and treated with 0.5 N aqueous HCl cold solution (50 mL). The precipitate obtained was collected on a filter and washed with water. The solid was purified on a silica gel column (hexane:ethyl acetate/2:1) to give the title compound as an off-white solid (10 mg, 4.6%): mp 212-213° C.; 1H-NMR (CHCl3-d6) δ7.96 (s, 1H), 7.77 (s, 1H), 7.65 (d, 1H, J=7.8 Hz), 7.60 (d, 1H, J=7.69 Hz), 7.51 (d, 1H, J=7.77 Hz), 7.45 (dd, 1H, J=8.67, 2.21 Hz), 7.31 (d, 1H, J=1.55 Hz), 6.91 (d, 1H, J=8.19 Hz), 1.8 (s, 6H); MS (EI) m/z 302 ([M+], 30%).

Workup

  1. additionwas added at rt under nitrogen cuprous cyanide (0.193 g, 2.2 mmol)
  2. additionAfter addition
  3. temperatureThe reaction mixture was then cooled to rt
  4. customThe precipitate obtained
  5. customwas collected on
  6. filtrationa filter
  7. washwashed with water
  8. customThe solid was purified on a silica gel column (hexane:ethyl acetate/2:1)

Sources & evidence

ORD record
ord-5f153cdb49ad45c6bb0defe18c4c5d30
Source dataset
uspto-grants-2003_01
Patent number
US06509334B1

Reaction notes

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