Trimethylsilylacetylene → HCID 86661615, compound

HRID 1496919Notes

Reaction equation

HRID 1496919 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][O:9][C@@H:10]2[CH2:15][O:14][C:13]3=[N:16][C:17]([N+:19]([O-:21])=[O:20])=[CH:18][N:12]3[CH2:11]2)=[N:6][CH:7]=1.[C:22]([Si](C)(C)C)#[CH:23]>CN(C=O)C.CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[C:22]([C:2]1[CH:3]=[CH:4][C:5]([CH2:8][O:9][C@@H:10]2[CH2:15][O:14][C:13]3=[N:16][C:17]([N+:19]([O-:21])=[O:20])=[CH:18][N:12]3[CH2:11]2)=[N:6][CH:7]=1)#[CH:23]

Participants

7

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 49852038HCID 49852038, compound

Product 1

HCID 86661615HCID 86661615, compoundYield 68%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of bromide 59 (see Example 21) (0.310 g, 0.873 mmol), PdCl2(PPh3)2 (33 mg, 0.047 mmol) and copper iodide (18 mg, 0.095 mmol) in DMF (4 mL) and Et3N (4 mL) was purged with N2. Ethynyltrimethylsilane (0.61 mL, 4.3 mmol) was added and the mixture was stirred in a sealed tube at 50° C. for 18 h, and then partitioned between EtOAc and water. The residue was dissolved in THF (20 mL), cooled to 0° C. and treated with TBAF (1M in THF, 1.8 mL), and then the solution was stirred for 2 h. Removal of the solvent gave a residue which was partitioned between EtOAc and water. Column chromatography of the organic portion on silica gel using gradient elution (0-5% MeOH:EtOAc) gave (6S)-6-[(5-ethynyl-2-pyridinyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (97) (0.178 g, 68%) as a tan solid: mp 135-136° C.; 1H NMR [(CD3)2SO] δ 8.61 (d, J=1.6 Hz, 1H), 8.02 (s, 1H), 7.90 (dd, J=8.0, 2.2 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 4.78 (d, J=13.8 Hz, 1H), 4.74 (d, J=13.8 Hz, 1H), 4.69 (dt, J=12.0, 2.6 Hz, 1H), 4.49 (d, J=12.0 Hz, 1H), 4.40 (s, 1H), 4.30-4.35 (m, 2H), 4.25 (dd, J=13.7, 3.5 Hz, 1H). Anal. (C14H12N4O4) C, H, N.

Workup

  1. customwas purged with N2
  2. custompartitioned between EtOAc and water
  3. dissolutionThe residue was dissolved in THF (20 mL)
  4. temperaturecooled to 0° C.
  5. additiontreated with TBAF (1M in THF, 1.8 mL)
  6. stirringthe solution was stirred for 2 h
  7. customRemoval of the solvent
  8. customgave a residue which
  9. customwas partitioned between EtOAc and water
  10. washColumn chromatography of the organic portion on silica gel using gradient elution (0-5% MeOH:EtOAc)

Sources & evidence

ORD record
ord-28ce885df62d4597ad4455eaa2a6e6fd
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

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