Ammonia → HCID 67370525, compound

HRID 1753180Notes

Reaction equation

HRID 1753180 reaction equation
[N:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[N:10]3[CH2:13][CH2:14][N:15]([C:16]([C:18]4[C:19]([CH3:23])=[N:20][O:21][CH:22]=4)=[O:17])[C:9]3([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[CH2:8][N:7]2[CH:32]=1)=[N+:2]=[N-:3].[C:33]([Si:35]([CH3:38])([CH3:37])[CH3:36])#[CH:34].C(N(C(C)C)C(C)C)C.[NH4+].[Cl-].N>CN(C=O)C.[Cu](I)I>[CH3:31][O:30][C:27]1[CH:28]=[CH:29][C:24]([C:9]23[N:15]([C:16]([C:18]4[C:19]([CH3:23])=[N:20][O:21][CH:22]=4)=[O:17])[CH2:14][CH2:13][N:10]2[C:11](=[O:12])[C:6]2[N:7]([CH:32]=[C:4]([N:1]4[CH:34]=[C:33]([Si:35]([CH3:38])([CH3:37])[CH3:36])[N:3]=[N:2]4)[CH:5]=2)[CH2:8]3)=[CH:25][CH:26]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 86657086HCID 86657086, compound

Product 1

HCID 67370525HCID 67370525, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 7-azido-10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (50 mg, 0.116 mmol) in DMF (2.5 mL) at 0° C. was added ethynyl-trimethyl-silane (33 μL, 0.23 mmol) followed by ethyl-diisopropyl-amine (24 μL, 0.14 mmol) and copper iodide (11 mg) and the mixture was stirred at 0° C. After one hour the reaction was complete (monitored by LCMS). A saturated aqueous solution of NH4Cl containing a drop of ammonia was added and the mixture extracted with EtOAc (3 times). The organics were washed with brine, dried (Na2SO4), filtrated and concentrated in vacuo. The resulting material was purified by flash chromatography (Biotage SP4, gradient 50-100% EtOAc in hexanes 10 CV; hold 100% EtOAc 7CV) to give 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-7-[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]-pyrazin-5-one (14 mg, yield: 23%). ESI-MI m/z [M+H]+ 532.2.

Workup

  1. extractionthe mixture extracted with EtOAc (3 times)
  2. washThe organics were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltrated
  5. concentrationconcentrated in vacuo
  6. customThe resulting material was purified by flash chromatography (Biotage SP4, gradient 50-100% EtOAc in hexanes 10 CV; hold 100% EtOAc 7CV)

Sources & evidence

ORD record
ord-ddd59033480c465ab1028ce4387432d2
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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